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A  TEXT-BOOK 

of 

PHYSIOLOGY 

For 

STUDENTS  AND  PRACTITIONERS  OF  MEDICINE 


By 

RUSSELL  BURTON-OPITZ 

S.  M.,  M.  D.,  Ph.D. 

Associate  Professor  of  Physiology,  Columbia  University;  Professorial 

Lecturer  in  Physiology  in  Teachers  College  and  the 

Extension  Department  of  Columbia  University 


ILLUSTRATED 


PHILADELPHIA  AND  LONDON 

W.  B.  SAUNDERS  COMPANY 

1920 


Copj-right,  1920    by  W.  B.  Saunders  Company 


^^0 


PRINTED     tN      AMemCA 

PRESS     OF 

B.     SAUNDCRS     COMPAQ 

PHr(_AOEI.PMIA 


PREFACE 


In  this  book  is  ombodiod  in  large  part  the  subject  matter  of  a 
series  of  lectures  which  it  has  l)een  my  privilege  to  deliver  annually 
to  the  students  of  the  College  of  Physicians  and  Surgeons  of  Columbia 
Universitj'.  Fully  realizing  that  the  medical  student  is  pressed  for  time 
and  is  imbitked  with  a  definite  desire  to  apply  his  physiological  knowl- 
edge in  a  practical  way  at  the  bedside,  it  has  l^een  my  endeavor  to 
invade  the  field  of  Comparative  Physiology  no  farther  than  is  abso- 
lutely necessary  to  form  a  thorough  basis  for  the  physiological  problems 
which  are  of  special  importance  to  medical  men.  For  this  reason, 
I  have  usually  allowed  the  different  discussions  to  be  preceded  by  brief 
remarks  of  a  more  general  character,  hoping  thereby  to  retain  a  happy 
medium  between  Special  Physiology  and  Comparative  Physiology. 

The  same  principle  I  have  followed  with  regard  to  Physics  and 
Chemistry.  While  the  medical  student  of  the  present  day  has  been 
required  to  pass  a  certain  number  of  courses  in  these  subjects  prelimi- 
nary to  the  studj^  of  medicine,  I  realize  that  time  stimulates  forget- 
fulness,  and  that  he  may  not  have  been  in  a  particularly  favorable 
position  during  his  years  at  College  to  grasp  the  practical  bearing  of 
many  of  the  topics  then  dealt  with.  For  this  reason,  I  have  thought  it 
advantageous  to  him,  as  well  as  to  myself  as  a  teacher,  briefly  to  review 
those  physical  and  chemical  principles  which  are  more  directly  related 
to  the  subject  matter  of  Physiology.  The  same  course  I  have  followed 
pertaining  to  Histology. 

Together  with  Anatomy,  and  often  with  an  unmistakable  attitude 
of  charity.  Physiology  has  been  regarded  as  one  of  the  foundation 
stones  of  modern  medicine.  It  seems  to  me,  however,  that  this  mile- 
stone has  been  passed  some  time  ago,  and  that  the  sole  hope  of  modern 
medicine  is  Phj^siology,  or  in  a  larger  sense,  the  experimental  sciences. 
Since  it  may,  therefore,  be  contended  that  "Medicine  is  Physiology," 
the  student  should  make  a  conscientious  effort  to  become  thoroughly 
acquainted  with  this  subject.  It  is  by  no  means  an  easy  task  that  hes 
before  him,  but  having  fulfilled  this  duty,  the  reward  is  large,  because 
no  other  science  is  quite  so  interesting  as  Physiology,  and  no  other 
combines  theory  and  practice  so  happily.  I  venture  to  hope  that  this 
book  will  help  him  in  this  attempt,  in  spite  of  its  doubtlessly  many  short- 
comings, for  which  I  beg  his  generous  indulgence. 

Inasmuch  as  the  subject  of  Physiology.is  altogether  too  large  to 
be  dealt  with  in  detail  within  the  space/of  an  ordinary  text-book, 
brevity  and  the  elimination  of  everything  that  may  be  considered  of 


6  PREFACE 

minor  importance,  are  essential.  The  material  gained  in  the  course 
of  this  process  of  elimination,  merits  no  further  abridgment  and  the 
student  should  acquire  a  thorough  working  knowledge  of  it.  In  re- 
cent years  our  phj^siological  literature  has  been  enriched  by  a  number 
of  very  admirable  text -books  upon  physiological  chemistry,  such  as 
those  of  Hammarsten,  ^Mathews,  Mcleod,  Bayliss,  Oppenheimer,  Lusk, 
Rubner,  and  Gautier.  I  am  deeply  sensible  of  my  obligations  to  these 
authors  for  the  material  I  have  gathered  from  their  writings.  But, 
since  this  field  has  been  so  minutely  covered  by  them,  I  have  not 
attempted  in  the  present  book  to  give  an\'thing  further  than  a  general 
story  of  these  events.  The  student  should  be  in  possession  of  at  least 
one  of  these  treatises  as  a  means  of  gathering  his  chemical  knowledge 
from  a  more  thorough  and  detailed  source  than  I  could  pos^)ly  present. 
It  has  been  my  endeavor  to  remain  as  much  as  possible  on  the  mechani- 
cal or  physical  side  of  Physiology  without,  however,  completely  elimi- 
nating its  chemical  aspect.  It  is  certainly  my  ardent  desire  to  keep 
Biological  Chemistry  within  the  fold  of  Physiology  in  a  relationship 
most  beneficial  to  both  sciences. 

Being  convinced  that  diagrams  and  simple  sketches  are  of  inesti- 
mable value  to  the  student,  I  have  inserted  in  the  present  book  a  large 
number  of  them.  Some  of  these  may  lay  claim  to  a  certain  originality, 
while  others  are  mere  modifications  of  earlier  sketches  of  a  similar 
kind.  For  the  latter  I  am  indebted  to  the  authors  and  publishers  of 
Quain's  Anatomy,  Herrick's  "Elements  of  Neurology,"  Schafer's  "Es- 
sentials of  Histology,"  Starhng's  "Human  Physiology,"  and  Howell's 
''Text-book  of  Physiology."  I  am  also  very  glad  to  acknowledge  my 
obhgation  to  the  pubhshers  of  Verworn's  "Allgemeine  Physiologic," 
Winterstein's  "Handbuch  der  vergleichenden  Physiologie,"  Nagel's 
^'Handbuch  der  Physiologie,"  Luciani's  "Fisiologia  Humana,"  and 
Oppenheimer's  "Handbuch  der  Biochemie."  The  chemical  subject 
matter  of  this  book  has  been  kept  in  close  conformity  to  this 
standard  work,  while  the  introductory  remarks  pertaining  to  the 
structural  and  functional  aspects  of  the  cell,  have  been  closely  allied 
to  the  well-known  treatises  of  Wilson  and  Verworn. 

R.  Burton-Opitz. 
Columbia  University, 
New  York  City, 

January,  1920 


CONTENTS 

PART  1 

THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

SECTION  I 
GENERAL  PHYSIOLOGY 

CHAPTER  1 

Page 

Living  Substance 17 

CHAPTER  II 
General  Phenomena  of  Life 29 

SECTION  II 
THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

CHAPTER  III 

Motion 36 

CHAPTER  IV 

The   Graphic  Registration  of  Muscular  Contraction.     Methods  of 
Stimulation  of  Muscle  and  Nerve 53 

CHAPTER  V 
Peculiarities  of  Muscle  Tissue 65 

CHAPTER  VI 
The  Character  of  the  Contraction  of  Muscle 70 

CHAPTER  VII 

The  Factors  Varying  the  Character  of  the  Contraction 76 

CHAPTER  VIII 
The  Character  of  the  Contraction  of  Smooth  Muscle 83 

CHAPTER  IX 
The  Chemistry  of  Muscle 85 

CHAPTER  X 
The  Production  of  Energy  in  Muscle 93 


8  CONTENTS 

SECTION  III 
THE  PHYSIOLOGY  OF  NERVE 

CHAPTER  XI 

Page 

The  Neuron  and  Its  Coxducti  xg  Paths 108 

CHAPTER  XII 
The  Phenomexa  of  CoxDrcTiox  ix  Xerve 124 

CHAPTER  XIII 

The  Reactiox  of  Xormal  axd  .\bxormal  Xerve  axd  Muscle  to  the  Con- 
stant AND  Interrupted  Electrical  Currents 142 

PART  II 

THE  BLOOD  AXD  LY:\IPH.     nOIUXITY 

SECTION  IV 

THE  BLOOD 

CHAPTER  XIV 
General  Characteristics  of  the  Blood 157 

CHAPTER  XV 
The  Chemical  Composition  of  the  Blood 168 

CHAPTER  XVI 
The  Red  Blood  Corpuscles 172 

CHAPTER  XVII 
The  White  Blood  Corpuscles 199 

CHAPTER  XVIII 
The  Blood  Platelets 207 

CHAPTER  XIX 
The  Coagulatiox"  of  the  Blood 211 

CHAPTER  XX 
The  Total  Quantity  and  Distribution  of  the  Blood — Loss  of  Blood.    .   226 


CONTENTS  9 

SF.CTION  V 
THE  LYMPH 

CHAPTER  XXI 

Page 

Properties  axd  Formation  of  Lymimi 233 

SECTION  VI 
RESISTANCE  AND  IMMUNITY 

CHAPTER  XXII 
The  Blood  and  Lymph  as  Protective  Mechanisms 245 

PART  III 

THE  CIRCULATION  OF  THE  BLOOD 

SECTION  VII 

THE  MECHANICS  OF  THE  HEART 

CHAPTER  XXIIl 
A  Comparative  Study  of  the  CiRctTLATORY  System 253 

CHAPTER  XXIV 
The  Arrangement  of  the  Musculature  of  the  Heart 263 

CHAPTER  XXV 
The  Cardiac  Cycle  (Revolutio  Cordis)  . 272 

CHAPTER  XXVI 
The  Phenomena  Noted  During  Each  Cardiac  Cycle 280 

SECTION  VIII 
THE  NERVOUS  REGULATION  OF  THE  HEART 

CHAPTER  XXVII 

Cardiac  Inhibition  and  Acceleration 309 

SECTION  IX 

FUNCTIONAL  PECULIARITIES  OF  THE  CARDIAC  MUSCLE 

TISSUE 

CHAPTER  XXVIII 
The  Origin  of  the  Heart  Beat 331 


10  CONTENTS 

CHAPTER  XXIX 

Page 
The  Physiological  Properties  of  Cardiac  Muscle 338 

SECTION   X 

THE  MECHANICS  OF  THE  CIRCULATION— 
HEMODYNAMICS 

CHAPTER  XXX 
Physical  Consideration 347 

CHAPTER  XXXI 

Blood  Pressure 354 

CHAPTER  XXXII 

The  Pulsatory  Variations  in  Blood  Pressure 377 

CHAPTER  XXXIII 
The  Blood  Flow 394 

SECTION  XI 
THE  NERVOUS  REGULATION  OF  THE  BLOOD-VESSELS 

CHAPTER  XXXIV 

The  Innervation  of  the  Blood-vessels  of  Different  Organs 411 

CHAPTER  XXXV 

The  Circulation  Through  Special  Organs 427 

PART  IV 
RESPIRATION,  VOICE  AND  SPEECH 

SECTION  XII 
RESPIRATION 

CHAPTER  XXXVI 
The  Structure  and  Function  of  the  Elementary  Lung 445 

CHAPTER  XXXVIl 
The  Mechanics  of  the  Respiratory  Movements 454 

CHAPTER  XXXVIII 

The  Frequency  and  Character  of  the  Respiratory  Movements     .    .   472 


CONTENTS  11 

CHAPTER  XXXIX 

Pace 

The  Chemistry  of  Respikation 4gg 

CHAPTER  XL 

The  Seat  and  Nature  of  the  Oxidations 508 

CHAPTER  XLI 
The  Respiratory  Interchange  under  Difp^erent  Conditions 514 

CHAPTER  XLII 
The  Nervous  Regulation  of  Respiration 528 

SECTION  XIII 
VOICE  AND  SPEECH 

CHAPTER  XLIIl 
The  General  Arrangement  of  the  Phonating  Organs 540 

CHAPTER  XLIV 
Phonation 549 

t 

PART  V 
THE  CENTRAL  NERVOUS  SYSTEM 

SECTION  XIV 

THE    FUNCTIONAL    SIGNIFICANCE     OF    THE    NERVOUS 

SYSTEM 

CHAPTER  XLV 

The  Structural  Arrangement  of  the  Nervous  System 557 

CHAPTER  XL VI 
The  Functional  Arrangement  of  the  Nervous  System 565 

CHAPTER  XL VII 
The  Functional  Unit  of  the  Nervous  System 574 

CHAPTER  XL VIII 
Reflex  Action 583 


12  CONTENTS 

SECTION  XV 
THE  FUNCTIONS  OF  THE  SPINAL  CORD 

CHAPTER  XLIX 

Page 

The  Spinal  Cord  as  a  Reflex  Center — Its  Power  of  Automaticity .       594 

CHAPTER  L 
The  Spinal  Cord  as  a  Conducting  Path.     Its  Trophic  Function  ....  603 

SECTION  XVI 
THE  AUTONOMIC  NERVOUS  SYSTEM 

CHAPTER  LI 
The  St-mpathetic  and  Parasympathetic  Systems 627 

SECTION  XVII 

THE  MEDULLA  OBLONGATA  AND  THE  CRANIAL 

NERVES 

CHAPTER  LII 

The  Function  of  the  Medulla  Oblongata 640 

CHAPTER  LIII 
The  Cranial  Xer-v-es 642 

SECTION  XVIII 
THE  CEREBRUM 

CHAPTER  LIV 
The  General  Function  of  the  Cerebrum 657 

CHAPTER  LV 
Cerebral  Localization 671 

CHAPTER  LVI 
Cerebral  Localization  (Continued) 681 

SECTION  XIX 

THE  CEREBELLUM.     THE  PROTECTIVE  MECHANISM  OF 
THE  NERVOUS  SYSTEM 

CHAPTER  LVII 
The  Cerebellum 706 


CONTENTS  13 

CIIAPTKR  LVIIl 

Page 

The  Protective  Mechanisms  of  the  Nervous  System 716 

PART  VI 
THE  SENSE-ORGANS 

SECTION  XX 
SPECIAL  SOMATIC  AND  VISCERAL  RECEPTORS 

CHAPTER  LIX 

Classification  of  the  Sense-organs 727 

CHAPTER  LX 

The  Senses  of  Pressure  or  Touch,  Pain,  and  Temperature 734 

CHAPTER  LXI 

The  Senses  of  Smell,  Taste,  Hunger  and  Thirst 743 

SECTION  XXI 
THE  SENSE  OF  HEARING 

CHAPTER  LXll 
The  Cause  and  Character  of  the  Sound  Waves 756 

CHAPTER  LXIIl 
The  External  and  Middle  Portions  of  the  Ear 763 

CHAPTER  LXIV 

The  Internal  Ear  or  Labyrinth 771 

SECTION  XXII 
THE  SENSE  OF  EQUILIBRIUM 

CHAPTER  LXV 
The  Sense  of  Position.     Static  Sense 781 

CHAPTER  LXVI 

The  Sense  of  Movement — Dynamic  Sense 785 


14  CONTENTS 

SECTION  XXIII 
THE  SENSE  OF  SIGHT 

CHAPTER  LXVII 

Page 

Physiological  Optics      794 

CHAPTER  LXVIII 
The  Globe  of  the  Eye  and  Its  Protective  Appendages 803 

CHAPTER  LXIX 
The  Cornea,  Iris  and  Aqueous  Humor 809 

CHAPTER  LXX 

The  Ciliary  Body  and  Lens 819 

CHAPTER  LXXI 
The  Retina 831 

CHAPTER  LXXII 

The  Formation  of  the  Image  upon  the  Retina 846 

CHAPTER  LXXIII 
Abnormalities  in  the  Refraction  of  the   Eye 853 

CHAPTER  LXXIV 
Binocular  Vision      869 

CHAPTER  LXXV 
Color  Vision 879 

PART  VII 

SECRETION 

SECTION  XXIV 
THE  EXTERNAL  SECRETIONS 

CHAPTER  LXXVI 
The  Group  of  the  Cutaneous  Secretions 891 

CHAPTER  LXXVII 
The  Lymphatic  and  Mucous  Secretions 903 


CONTENTS  15 

CHAPTER  LXXVIII 

Page 

The  Digestive  Secretions 908 

CHAPTER  LXXIX 
The  Digestive  Secretions  (Continued) 918 

CHAPTER  LXXX 
The  Digestive  Secretions  {Continued) 938 

SECTION  XXV 
THE  INTERNAL  SECRETIONS 

CHAPTER  LXXXI 

The  Thyroid  and  Parathyroid  Bodies.     The  Thymus,  Liver,  and  Pan- 
creas      951 

CHAPTER  LXXXII 
The  Adrenal  Bodies,  Hypophysis,  Pineal  Gland,  Testes  and  Ovaries.   .   967 

PART  VIII 
METABOLISM 

SECTION  XXVI 
DIGESTION 

CHAPTER  LXXXIII 
The  Chemistry  of  Digestion 985 

CHAPTER  LXXXIV 
The  Mechanics  of  Digestion 998 

SECTION  XXVII 
ABSORPTION 

CHAPTER  LXXXV 

The  Absorption  of  the  Reduced  Foodstuffs  from  the  Alimentary 
Canal 1022 

CHAPTER  LXXXVI 
The  History  of  the  Different  Foodstuffs  in  the  Body 1037 


16  CONTENTS 

CHAPTER  LXXXVII 

Page 
The  Metabolic  Requirements  of  the  Body ....    1052 

CHAPTER  LXXXVIII 

The  Xutritxae  V.^lue  of  Food 1058 

SECTION  XXVIII 
EXCRETION 

CHAPTER  LXXXIX 
The  Secretion  of  Urine 1064 

CHAPTER  XC 
The  Expulsion  of  the  Urine.     Micturition 1075 

CHAPTER  XCI 
The  Composition  of  the  Urine 1080 

SECTION  XXIX 
ANIMAL  HEAT 

CHAPTER  XCII 
The  Production  and  Dissipation  of  Heat 1089 

PART  IX 

REPRODUCTION 

SECTION  XXX 
THE  REPRODUCTIVE  ORGANS 

CHAPTER  XCIIl 
Growth,  Regeneration  and  Reproduction 1109 

CHAPTER  XCIV 
The  Male  and  Fe.male  Reproductive  Organs 1122 

CHAPTER  XCV 
The  Development  of  the  Embryo 1135 

Index 114" 


PART  I 

THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

SECTION  I 
GENERAL  PHYSIOLOGY 


CHAPTER  I 
LIVING  SUBSTANCE 

Definition  and  Scope. of  Physiology. — The  science  of  physiology 
deals  with  the  processes  occurring  in  living  matter.  It  is  the  study  of 
the  dynamics  of  life  and  as  such  should  be  extended  to  the  entire 
realm  of  living  entities,  to  animals  as  well  as  to  plants,  and  to  simple 
as  well  as  to  complex  organisms.  Physiology,  however,  deals  solely 
with  the  functional  aspect  of  living  substance,  its  structural  char- 
acteristics being  taken  care  of  by  the  sciences  of  morphology,  anatomy 
and  histology.  But  inasmuch  as  an  analysis  of  the  function  of  a  part 
cannot  well  be  attempted  without  a  thorough  understanding  of  its 
structure,  it  must  be  clear  that  the  best  results  can  only  be  obtained  if 
these  sciences  are  brought  into  the  closest  possible  relationship.  A 
study  of  the  function  of  the  eye  is  scarcely  feasible  without  having 
obtained  first  of  all  a  clear  conception  of  the  general  arrangement  and 
structural  details  of  the  tissues  entering  into  its  formation.  This  is 
also  true  of  the  ear,  the  heart,  the  brain  and  all  other  organs  of  our 
body.  Physiology,  therefore,  presents  itself  as  an  important  unit 
of  the  science  of  biology,  which  takes  cognizance  of  all  things  possessing 
life,  as  follows: 

Origin  and  Development;  Embryology. 

f  o  1    A/r       LI  [  Histology  of  Plants 

General;  Morphology        „•,„,::,    .  a„;^„i 


Biology 


Structure 


Function 


[  Histology  of  Animals 


[  Anatomy 
Special  |  Phytomy 

[  Zootomy 
General  Physiology 


[  Lower  Vertebrates 


Special  Physiology  |  Mammals 
[  Man 
17 


18  GENERAL    PHYSIOLOGY 

The  analysis  of  the  phenomena  of  hfe  also  necessitates  as  a  pre- 
requisite an  adequate  knowledge  of  physics  and  chemistry.  Without 
these  sciences  physiological  progress  would  indeed  be  slow  or  even 
impossible.  This  fact  accounts  in  a  way  for  the  almost  exclusive 
position  which  anatomy  has  enjoyed  until  comparatively  recent 
years.  As  the  acquisition  of  gross  structural  data  is  not  at  all  depend- 
ent upon  the  development  of  the  supplementary  sciences,  anatomy 
has  been  able  to  advance  practically  without  restrictions  of  any  kind. 
At  the  close  of  the  nineteenth  century  it  had  thus  acquired  an  almost 
dominating  position.  On  the  functional  side,  scarcely  any  progress 
was  made  until  the  beginning  of  the  sixteenth  century,  when  Paracel- 
sus (1493-1541)  attacked  the  doctrines  of  Gahnus  (131-200)  and 
developed  a  physiological  system  of  his  own.  Greatly  aided  by  the 
anatomical  discoveries  of  Vesalius,  Eustachius,  Faloppio  and  Serveto, 
it  was  left  to  Harvey  (1578-1657)  to  unravel  the  secrets  of  the  circu- 
lation of  the  blood.  This  discovery  put  an  end  to  speculative  physi- 
ology and  initiated  experimental  physiological  methods.  Harvey, 
moreover,  propounded  a  doctrine  which  was  destined  to  exert  a  pro- 
found influence  upon  the  development  of  modern  physiology,  namely, 
his  doctrine  ''de  generatione  animahum."  In  recent  years  this  work 
has  dominated  our  views  regarding  the  origin  of  animal  life  and  has  led 
to  the  dictum  of  "omne  vivum  ex  ovo." 

The  seventeenth  century  is  a  memorable  one  for  physiology, 
because  it  produced  a  Copernicus,  a  Galileo,  a  Descartes,  a  Boyle 
and  a  Newton,  thus  furthering  our  knowledge  of  physics.  Of  scarcely 
lesser  importance,  however,  is  the  construction  of  the  compound 
microscope  which  made  the  histological  discoveries  of  Leeuwenhoek 
(1632-1723),  Malpighi  (1628-1694)  and  Swammerdam  (1637-1685) 
possible.  Then  followed  Albrecht  v.  Haller  (1708-1777)  who  not 
only  greatly  promoted  the  experimental  side  of  physiology  but  also 
combined  the  data  then  known  into  a  homogeneous  whole  and  thus 
gave  an  independent  existence  to  our  Science.  At  about  this  time 
were  made  the  far  reaching  chemical  discoveries  of  Priestley  (1773- 
1804),  Lavoisier  (1743-1794)  and  Girtanner  (1760-1800). 

The  period  from  1800  to  about  1860  is  commonly  regarded  as 
the  renaissance  period  of  physiology.  It  is  dominated  by  such  men 
as  Johannes  v.  Muller  (1801-1858)  and  Johannes  Purkinje  and,  on 
the  chemical  side,  by  Wohler  (1800-1882) ^  and  v.  Liebig  (1803-1873). 
Physiology  at  once  began  to  profit  by  the  discoveries  in  chemistry, 
because  they  found  immediate  apphcation  in  the  investigations  of 
problems  connected  with  respiration,  digestion  and  secretion.  From 
this  time  on  physiology  shows  two  tendencies,  namely  a  physical 
and  a  chemical.     Very  fortunately,  however,  this  division  has  re- 

1  Mention  is  usually  made  of  Wohler,  because  he  succeeded  in  1828  in  producing 
urea  synthetically.  In  reality,  however,  this  synthesis  was  preceded  by  several 
others,  namely,  by  that  of  alcohol  (Hennel),  that  of  acetic  acid  (Dobereiner, 
1822)  and  that  of  oxalic  acid  (Scheele,  1776).    . 


LIVING    SUBSTANCE  19 

maincd  largely  theoretical  until  more  recently,  although  it  is  quite 
true  that  an  expert  knowledge  of  more  than  one  of  these  fundamental 
sciences  can  scarcely  be  demanded  of  any  physiologist.  This  new 
tendency  soon  forced  physiologists  to  confine  their  constructive  work 
either  to  physical  or  to  chemical  physiology.  The  former  group  of 
investigators  includes  such  men  as  E.  H.  Weber  (1795-1878),  Volk- 
mann  (1801-1877),  Ludwig  (1816-1895),  Helmholtz  (1821-1894),  Du 
Bois-Reymond  (1818-1896),  Marey  (1830-1904),  Bernard  (1813-1878); 
and  the  latter,  such  men  as  Voit  (1831-1908),  Pfluger  (1829-1910), 
Kossel  (1853),  Zuntz  (1847),  and  Hofmeister  (1808-1878). 

Physiology,  therefore,  belongs  essentially  to  the  nineteenth  cen- 
tury. It  is  a  comparatively  new  science,  but  is  unfolding  itself 
very  rapidly,  so  that  it  now  forms  the  chief  basis  of  modern  medicine. 
This  is  the  age  of  the  experimental  sciences  and  very  rightly  so, because 
in  them  lies  our  greatest  hope  of  benefiting  mankind.  As  Verworn 
expresses  it,  the  struggle  for  existence  forces  man  to  master  the  forces 
of  nature  and  to  eradicate  all  those  which  tend  to  enfeeble  him. 
Physiology  constitutes  a  means  which  is  used  chiefly  to  combat  the 
latter.  Its  ultimate  object,  therefore,  is  the  welfare  of  mankind. 
In  order  to  attain  this  end,  it  cannot  confine  itself  to  man  and  the 
higher  animals,  but  must  include  Hving  matter  wherever  found, 
even  that  forming  the  most  primitive  organisms  and  plants.  For 
this  reason,  physiology  does  not  always  present  a  wholly  practical 
aspect,  but  follows  at  times  a  purely  scientific  course  of  inquiry. 
The  results  of  the  latter,  however,  are  not  to  be  undervalued,  because 
as  man  is  not  accessible  to  physiological  methods,  excepting  in  a  few 
special  instances,  we  are  constantly  forced  to  base  our  conclusions 
upon  the  fundamental  processes  displayed  by  the  lower  forms  of  life. 
That  a  direct  comparison  of  this  kind  is  permissible  iii  most  cases, 
has  been  fully  demonstrated  experimentally. 

Animate  and  Inanimate  Material. — Since  physiology  purposes  to 
analyze  the  phenomena  of  life,  it  becomes  necessary  to  familiarize  our- 
selves with  the  fundamental  characteristics  of  living  substance.  The 
layman  most  generally  places  the  greatest  stress  upon  the  production 
of  mechanical  energy,  such  as  is  evinced  by  those  apparently  spon- 
taneous movements  which  are  made  use  of  by  living  entities  in  chang- 
ing their  position  in  space.  As  a  last  means  of  differentiation  between 
animate  and  inanimate  bodies  he  employs  those  activities  which  are 
associated  with  respiration  and  the  action  of  the  heart.  A  more  far- 
reaching  differentiation,  however,  may  be  attempted  upon  the  basis 
of  morphological,  genetic,  physical  and  chemical  peculiarities.^  Thus, 
it  has  been  said  that  inorganic  bodies  possess  definite  geometric  pro- 
portions, and  that  they  contain  no  organs  and  exhibit  the  simplest 
possible  organization.  A  brief  survey,  however,  will  show  that  these 
characteristics  are  also  presented  by  living  substance,  because  organ- 

1  Verworn,  Allgemeine  Physiologie,  Jena,   1909;  and  Irritability,  Yale  Univ 
Press,  1913. 


20  GENERAL    PHYSIOLOGY 

isms  with  mathematical  contours  arc  very  numerous  (radiolaria)  and 
many  of  them  tlo  not  exhibit  a  differentiation  of  their  protoplasm  nor 
a  division  of  function  (amoeba).  Upon  the  genetic  basis,  it  is  usually 
stated  that  organisms  can  only  originate  from  organisms.  But  if  we 
adhere  to  that  theory  regarding  the  origin  of  life  which  assumes  that 
the  first  cell  arose  in  consequence  of  a  combination  of  inorganic  sub- 
stances at  a  time  when  conditions  upon  this  earth  permitted  this  union 
to  take  place/  this  difference  cannot  be  said  to  be  of  fundamental 
importance.  It  is  conceivable  that  living  matter  appeared  as  a  result 
of  the  evaporation  of  water  containing  the  common ,  salts.  In  the 
course  of  this  concentration  cyanides  and  other  similar  organic  com- 
pounds were  formed  in  consequence  of  vigorous  electrical  disturbances. 
These  elementary  organic  globules  eventually  gave  rise  to  cells  and 
by  descendance  to  all  the  organisms  inhabiting  this  earth.-  It  is  a 
well-known  fact  that  inorganic  substances  are  constantly  made  use  of 
by  plants  in  their  production  of  organic  material  and  lastly,  it  must 
be  taken  into  account  that  not  all  organisms  give  rise  to  their  like. 
For  example,  the  workers  of  the  bees  and  ants  are  sexually  retrogressive 
and  do  not  possess  the  power  of  reproduction. 

The  statement  has  also  been  made  that  living  substance  possesses 
the  properties  of  irritability  and  contractility,  while  inorganic  material 
does  not.  But  if  we  observe  an  ordinary  reaction  between  substances 
occurring  in  a  test  tube,  we  cannot  fail  to  recognize  that  even  inorganic 
matter  is  receptive  and  gives  rise  to  motion.  This  is  especially  true 
of  those  substances  which  cause  reactions  of  an  explosive  kind,  such  as 
nitroglycerin.  The  energy  liberated  by  this  body  when  stimulated, 
can  scarcely  be  duplicated,  and  hence,  with  the  exception  of  the  fact 
that  inorganic  material  presents  an  irritability  and  contractility  of  a 
type  somewhat  different  from  that  shown  by  living  substance,  this 
ba^sis  does  not  furnish  an  actual  means  of  differentiation. 

If  living  substance  is  studied  from  the  standpoint  of  chemistry,  it 
is  found  that  it  contains  certain  organic  bodies  the  complexity  of 
which  is  not  equalled  in  the  inorganic  world.  Indeed,  one  of  these 
groups,  the  proteids,  forms- a  constant  constituent  of  protoplasm,  while 
no  substance  can  be  found  in  the  inorganic  world,  which  at  all  ap- 
proaches the  complexity  of  the  proteid  molecule.  It  is  true,  however, 
that  even  this  difference  must  disappear  as  soon  as  a  way  has  been 
found  to  produce  these  bodies  artificially.  There  is  one  peculiarity, 
however,  which  is  decisive  and  that  is  the  specific  metabolic  function 
of  living  matter.  Not  only  is  it  capable  of  altering  its  composition 
constantly,  but  also  of  giving  off  certain  waste  products  which  are 
subsequently  replaced  by  new  material.  Life,  therefore,  is  character- 
ized by  nothing  more  than  a  specific  metabolism  of  certain  substances 
and  especially  of  the  proteins.  In  a  very  general  way,  however,  it  is 
permissible  to  state  that  living  substance  is  distinguished  from  life- 

^  Preger:  Die  Hypothesen  iiber  den  Ursprung  des  Lebens,  Berlin,  1880. 
*  E.  Hackel:  Gen.  Morph.  der  Organismen,  Berlin,  1866. 


LIVING    SUBSTANCE  21 

less  material,  whetluT  inorganic  or  organic,  by  its  properties  of  irritabil- 
ity, conductivity,  contractility,  metabolism  and  reproduction. 

The  Structural  Basis  of  Life. — While  living  substance  appears  in 
many  forms,  it  always  picstMits  itself  as  an  entit}^  which  is  capable  of 
leading  an  indepiMident  existence.  It  is  living  organic  material  and 
as  such  is  generally'  arranged  in  the  form  of  cells.  In  a  general  way,  it 
may  be  said  that  this  term  is  applied  to  the  smallest  particles  of  living 
substance  still  capable  of  existing  independently  of  others.  Hence, 
the  cell  represents  the  simplest  type  of  individuality  of  living  substance 
and  constitutes  a  unit  in  structure  as  well  as  in  function. 

It  is  true,  however,  that  our  conception  of  a  cell  is  not  at  all  concise, 
because  cells  may  exhibit  very  different  characteristics.  To  begin 
with,  the  term  "cell"  was  employed  by  botanists  to  describe  those 
structural  units  which  make  up  the  stem  and  the  leaves  of  plants. 
In  a  similar  way  it  was  found  later  on  that  the  orgaiis  and  tissues 
of  the  higher  animals  are  not  composed  of  homogeneous  masses  of 
Hving  substance,  but  of  a  multitude  of  very  small  particles  which  are 
separated  from  one  another  by  partitions.  In  both  instances  the  cell 
was  finally  observed  to  be  a  definite  unit  of  the  entire  mass,  consisting 
of  a  membrane  investing  a  semi-sohd  globule  of  protoplasm  and  a  dark 
body,  or  nucleus. 

It  soon  became  evident  that  this  conception  is  not  absolutely  cor- 
rect, because  the  studies  of  Schultze^  upon  the  structure  of  the  rhizo- 
pods  proved  that  there  are  organisms  in  existence  which  are  not  sur- 
rounded by  a  cell  membrane,  but  appear  merely  as  naked  masses  of 
living  substance  possessing  the  same  characteristics  as  the  viscous 
contents  of  the  plant  cell,  or  protoplasm.  In  accordance  with  this 
discovery,  it  has  since  been  held  that  the  essential  unit  of  the  cell  is 
the  protoplasm,  i.e.,  the  cell  consists  merely  of  a  globule  of  protoplasm 
which  may  or  may  not  be  invested  by  a  membrane.  Our  original 
idea  regarding  its  structure  has  also  been  modified  in  so  far  as  the 
nucleus  is  no  longer  regarded  as  an  essential  constituent.  This  con- 
ception necessitated  a  different  interpretation  of  the  discovery  of 
Brown^  than  that  ordinarily  given  to  it.  It  will  be  remembered  that 
this  investigator  noted  that  protoplasm  embraces  a  granule  possessing 
the  power  of  refracting  Hght.  Triis  fact  was  greatly  amplified  later 
on  bj'  Schleiden^  and  Schwann^  who  found  this  granule  so  universally 
present  that  they  considered  it  as  a  constant  constituent  of  the  cell. 
Hackel,^  however,  proved  subsequently  that  many  rhizopods  do  not 
contain  a  nucleus.  In  more  recent  years  this  condition  has  also  been 
showm  to  prevail  in  bacteria  and  fungi.  It  seems  best,  however,  not 
to  emphasize  this  point  too  strongly,  because  while  many  cells  do  not 

1  Archiv  fiir  Anat.  und  Physiol.,  1861. 

-  Transact,  of  the  Linnean  Soc,  London,  1833. 

^  MuUer's  Archiv,  1833. 

*  Mikr.  Unters.  iiber  die  Struktur  und  den  Wachstum  der  Tiere  and  Pflanzen, 
1839. 

*  Biolog.  Studien,  Leipzig,    1870. 


22  GENERAL    PHYSIOLOGY 

display  a  clearly  recognizable  nucleus,  they  nevertheless  contain  nu- 
clear material  which,  in  accordance  with  Biitschli,^  appears  in  many 
cases  merely  as  dust-like  fragments  scattered  through  the  cytoplasm. 
At  best,  therefore,  a  cell  can  only  be  defined  as  a  globule  of  protoplasm 
containing  a  certain  amount  of  nuclear  material. 

The  term  protoplasm  (protos,  first;  plasma,  form)  is  usually  em- 
ployed as  a  synonym  for  living  substance.  Huxley,  for  example, 
speaks  of  it  as  the  physical  basis  of  life,  just  as  the  cell  has  been  desig- 
nated by  Briicke"-^  as  the  elementay  functional  unit.  It  should  be 
emphasized,  however,  that  protoplasm  is  not  a  single  substance,  but 
is  composed  of  several.  It  is  a  definite  chemical  compound  which,  in 
accordance  with  the  histologists,  possesses  certain  staining  powers  and, 
in  accordance  with  the  physiologists,  exhibits  a  certain  behavior  to- 
ward the  conditions  under  which  it  is  made  to  live.  In  the  second 
place,  it  must  be  remembered  that  protoplasm  differs  somewhat  in  its 
chemical  composition  and  physical  arrangement.  Thus,  the  proto- 
plasm composmg  the  muscle  cell  is  not  at  all  identical  with  that  form- 
ing the  cells  of  the  liver  or  kidney  or  other  organs.  We  know  this  to 
be  true,  because  the  reactions  of  these  diverse  types  of  protoplasm  are 
not  absolutely  the  same,  but  vary  in  accordance  with  their  function. 
And  besides,  even  a  single  cellular  unit  most  commonly  contains  more 
than  one  kind  of  protoplasm,  namely,  the  fundamental  substance  plus 
certain  adjuncts  which  to  all  appearances  give  rise  to  a  division  of 
labor.  Thus,  it  is  conceivable  that  in  single  protoplasmic  entities, 
such  as  are  presented  by  ameba,  stentor  and  other  unicellular  organ- 
isms, a  certain  portion  of  the  substance  is  set  aside  to  serve  the  pur- 
pose of  digestion,  another  that  of  excretion  and  still  another  that  of 
locomotion. 

The  Structure  of  the  Cell. — It  is  evident,  therefore,  that  living 
matter  appears  in  the  form  of  cells  and  that  these  cells  may  be  either 
single  free-living  organisms  or  may  be  combined  into  colonies  to  form 
the  tissues  and  organs  of  the  more  complex  animals  and  plants.  In 
either  case,  whether  forming  a  unicellular  entity  or  united  with  others 
into  a  multicellular  organism,  the  cell  presents  certain  morphological 
and  functional  characteristics.  Its  form  differs  greatly,  and  while  the 
large  majority  of  cells  retain  their  shape  throughout  their  life,  a  cer- 
tain number  of  them,  such  as  the  ameba,  change  it  constantly.  It 
may  be  taken  for  granted,  however,  that  their  fundamental  shape  is 
round,  or  nearly  so,  and  that  almost  any  polyhedral  form  may  be  im- 
parted to  them  by  grouping  them  into  tissues  and  organs.  Moreover, 
while  some  of  them  may  attain  an  unusual  length,  others  are  equip- 
ped with  appendages  in  the  form  of  pseudopodia,  flagella  and  ciha. 
Their  size,  on  the  other  hand,  differs  only  within  relatively  narrow 
limits.  By  far  the  greatest  number  of  them  remain  below  the  range 
of   ordinary   vision   and   very   few  attain   dimensions  that  may   be 

^  Uber  den  Bander  Bakterien  und  verw.  Organismen,  Leipzig,  1890. 
*  Sitzungsber.  der  Wiener  Akad.  der  Wissensch.,  xliv,  1861. 


LIVING   SUBSTANCE  23 

expressed  in  millimeters.  The  latter  are  commonly  observed  to  possess 
ameboid  motion.  Consequently,  the  formation  of  a  bulky  organism 
is  possible  only  by  the  union  of  a  multitude  of  relatively'  independent 
cellular  elements. 

As  has  becMi  stated  above,  the  term  protoplasm  was  employed  origi- 
nally in  a  morphological  sense  to  designate  the  entire  mass  of  living 
substance  inside  the  cell  wall  with  the  exception  of  the  nucleus.  At 
the  present  time,  however,  we  know  that  this  conception  is  not  quite 
correct,  because  the  contents  of  the  cell  are  really  a  morphological  and 
chemical  mixture.  To  begin  with,  it  may  be  stated  that  a  cell  con- 
sists of  two  parts,  namely  of  cytoplasm  and  of  nuclear  material. 

The  cytoplasm  appears  as  a  clear  homogeneous,  viscous  "ground- 
substance"  in  which  are  embedded  varying  numbers  of  formed  ele- 
ments.^ At  times,  therefore,  the  watery  ground  substance  is  clearly 
in  evidence,  while  at  other  times  it  is  hidden  by  granular  material. 
The  formed  elements  of  the  cytoplasm  embrace  bodies  which  are  abso- 
lutely essential  to  the  life  of  the  cell  as  well  as  bodies  which  must  be 
regarded  as  accidental  admixtures.  Among  the  former  are  granules 
representing  all  stages  of  metabolism,  namely,  food  material  ready 
for  assimilation  and  the  products  of  the  cellular  processes  ready  for  ex- 
cretion. Some  of  the  latter  may  first  be  transported  to  distant  parts 
of  the  body  to  be  used  in  connection  with  some  other  function.  A  very 
important  constituent  of  the  cytoplasm  of  the  green  plants  is  the 
so-called  chloroplastic  material  which  appears  as  small  round  or  tape- 
shaped  bodies  containing  an  intense  green  pigment.  It  is  the  func- 
tion of  this  material  to  assimilate  the  carbon  dioxid  so  that  under  the 
energy  of  the  rays  of  the  sun  an  assimilation  of  starch  and  an  evolu- 
tion of  oxygen  may  be  had.  A  similar  substance  is  the  leukoplastic 
material  of  certain  plant  cells  which  serves  to  build  up  starch  from 
sugars.  At  times  the  cytoplasm  also  contains  globules  of  fluids,  the 
so-called  vacuoles,  which  may  be  either  quiescent  or  exhibit  rhythmic 
contractions.  Among  the  accidental  admixtures  may  be  mentioned 
the  indigestible  remnants  of  the  food,  such  as  pieces  of  the  shells, 
skeletons  or  capsules  of  the  organisms  which  have  been  ingested.  In 
fact,  the  cytoplasm  may  also  give  lodgment  to  living  organisms  and 
especially  to  certain  parasites. 

Under  the  low  power  of  the  microscope  the  ground-substance  of  the 
cytoplasm  presents  a  perfectly  homogeneous  hyaline  appearance; 
indeed,  such  objects  as  the  pseudopodia  of  the  ameba  and  rhizo- 
pods  do  not  display  a  differentiation  even  when  observed  under  high 
powers.  In  most  cases,  however,  some  kind  of  structure  may  then 
be  made  out.  Thus,  Remak-  has  shown  (1844)  that  ganglion  cells 
possess  a  fibrillar  interior,  while  Frommann  and  Heitzmann  have 
proved  (1867)  that  the  fundamental  structure  of  protoplasm  is  spongy. 

1  M.  Heidenhain,  Plasma  und  Zelle,  Jena,  1911. 

2  Archiv  fiir  Anat.  und  Physiol.,  1844. 


24 


GENERAL    PHYSIOLOGY 


Biitschli,^  in  fact,  believes  that  it  possesses  a  honeycomb  or  froth-like 
structure.  These  somewhat  divergent  views  may  be  classified  under 
the  following  heads: 

(a)  The  granula  theory-,  proposed  by  Altman,^  holds  that  the 
granules  contained  in  protoplasm  are  the  essential  constituent  and  that 
the  fluid  medium  is  not  living  substance  at  all. 

(6)  The  fibrillar  theors'  assumes  that  the  protoplasm  consists  of  a 
network  or  clusters  of  fibrils  containing  in  its  meshes  a  certain  amount 
of  fluid  material.     The  fibrillar  reticulum  or  spongework  is  designated 

by  Schafer  as  the  spongioplasm  and  the 
more  fluid  and  structureless  portion  as  the 
hyaloplasm. 

(c)  The  alveolar  theory-,  advocated  by 
BiitschU,  contends  that  the  ground-substance 
of  the  c\"toplasm  stores  its  material  as 
globules  which  gradually  increase  in  size 
and  become  separated  from  one  another 
by  alveolar  partitions.  ^Microscopic  for- 
mations of  this  kind  may  be  produced  artifi- 
cially by  mixing  oil  -with  potassium  or  cane 
sugar.  On  bringing  a  droplet  of  this  oil  in 
contact  with  water,  molecules  of  the  latter 
pass  inward  and  spht  the  oil  droplet  into 
innumerable  smaller  ones  until  a  ven,'  deU- 
cate  froth  is  produced.  The  diffusion  cur- 
rents resulting  in  this  mixture,  are  at  times 
so  intense  that  movements  similar  to  ame- 
boid motion  may  be  obser\'ed. 

The  nucle-iM  of  the  cell  appears  as  a  rule 
as  an  oval  or  round  body,  situated  near  the  center  of  the  cjiioplasm 
and  sharply  differentiated  from  it  by  what  is  known  as  a  nuclear 
membrane.  !Many  cells,  however,  contain  nuclei  which  are  long 
drawn  out  or  constricted  so  as  to  form  band-like  or  bead-like  chains 
of  nuclear  material,  while  in  others  the  nuclear  material  is  scattered 
through  the  cj'toplasm  in  the  form  of  dust-like  particles.  Consider- 
able variations  are  also  noted  with  regard  to  the  relative  volume  of 
the  nucleus  and  cytoplasm,  the  latter  forming  at  times  merely  a  narrow 
frame  around  a  large  centrally  placed  nucleus. 

The  nucleus  consists  of  an  enveloping  membrane,  a  network  of 
fibers,  the  nuclear  matrix  and  nucleoli.  It  is  believed  that  the  spongio- 
plasm of  the  cj'toplasm  is  extended  into  the  nucleoplasm,  but  on  a 
larger  scale,  i.e.,  the  threads  are  coarser  and  can  therefore  be  more 
easily  seen.  The  interstices  of  this  network  are  filled  with  nuclear 
sap  or  matrix.     At  the  different  points  of  crossing  of  the  filaments,  the 

^  Untersuchungen  uber  die  mikrosk.  .Schaiime  und  das  Protoplasma,  Leipzig, 
1892. 

'  Die  Elementarorg.  imd  ihre  Beziehiingen  zu  den  Zellen,  Leipzig,  1890. 


Lir'typ 


1. — The  .Stp.vctuez  of 
Protoplasm. 
An  epidermal  cell  of  the  earth- 
worm.    {After  Batschli.) 


Fig. 


LIVING    SUBSTANCE 


25 


chromatin,  of  which  they  arc  composed,  appears  in  the  forju  of  gran- 
ules. Some  of  thes(^  are  especially  conspicuous  and  arc  then  called 
pscudonucleoli.  Other  masses  of  chromatin,  the  true  nucleoli,  are 
sometimes  found  embedded  in  the  nuclear  sap.  If  the  cell  is  stained 
Avith  such  dyes  as  hematoxylin  or  safranin,  the  nucleus  is  made  to 
stand  out  prominently  against  the  light  protoplasmic  ground-sub- 
stance. The  nucleus,  however,  does  not  absorb  the  pigment  very 
evenly,  because  the  chromoplasmic  network  and  nucleoli  possess  a 
much  greater  aflfinity  for  it  than  the  matrix.  Herein  really  lies  the 
reason  for  saying  that  the  cell  is  composed  of  chromatic  and  achromatic 
substances;  the  former  combine  with  many  dyes  with  great  ease 
while  the  latter  do  not. 

Attnction-sphere  enclosing  two  centrosomes 


Plasmosome 
or  true 
nucleolus 

CUromatin- 
network 


Nucleus-^  LiniQ.network   — 


Karyosome, 
net-knot,  or 
chromatin- 
nucleolus 


Flastids  lying  in  the 
cytoplasm 


Passive  bodies  (meta- 
plasm  or  paraplasm) 
suspended  in  the  cy- 
toplasmic meshwork 


Fig.  2. — Diagram  of  a  Cell.     (Wilson.) 


The  Chemistry  of  the  Cell. — The  chemical  analysis  of  protoplasm 
as  practised  at  the  present  time,  necessitates  its  destruction  as  a 
functional  entity.  For  this  reason,  its  composition  can  only  be 
deduced  from  that  of  dead  organic  material.  KosseP  divides  its  con- 
stituents into  primary  and  secondary,  the  latter  being  present  only 
in  some  types  of  cells.  As  an  example  of  this  kind  might  be  mentioned 
the  glycogen  of  the  cells  of  the  liver.  As  primary  constituents  are 
to  be  regarded  lecithin,  cholesterin  (lipoids),  proteids  (nucleopro- 
teids),  inorganic  salts  and  water. 

As  lipoids  must  be  classified  all  those  bodies  which  may  be  extracted  with  ether 
or  similar  solvents.^  Whether  the  lecithin  which  belongs  to  the  class  of  the 
phosphatides,  is  actualh'  a  primary  constituent  of  the  cells  is  still  doubtful.     It  is 

1  Archiv  fiir  .\nat.  und  Physiol.,  1891. 

^  Overton,  Studien  liber  die  Narkose,  Jena,  1901. 


26  GENERAL   PHYSIOLOGY 

found  in  large  amounts  in  sperm-cells,  the  eggs  of  fishes,  nervous  tissue,  and  the 
yolk  of  eggs,  and  in  small  amounts  in  striated  and  cardiac  muscle  cells.  Cere- 
brosides,  i.e.,  bodies,  containing  nitrogen  but  no  phosphorus,  are  contained  in 
spermatozoa  and  leukocytes.  Fatty  acid  and  neutral  fat,  i.e.,  substances  contain- 
ing neither  nitrogen  nor  phosphorus,  are  very  common  constituents  of  cells;  the 
nucleus,  however,  is  said  to  be  free  from  fat.  Cholesterin,  one  of  the  substances 
belonging  to  this  group,  is  a  primary  constituent,  but  nothing  definite  regarding 
its  origin  and  condition  is  known.  The  lipoids  facilitate  the  solubility  of  those 
substances  which  are  otherwise  scarcely  soluble  in  water.  They  also  play  a  part 
in  hemolysis  and  absorption. 

The  proteins  are  the  most  constant  and  important  constituent  of  the  cell."^ 
They  occur  in  the  cytoplasm  as  well  as  in  the  nucleus  and  belong  chiefly  to  the  class 
of  the  proteids.  The  nucleoproteids  of  the  nucleus  are  to  be  sharply  differentiated 
from  the  proteins  of  the  cytoplasm,  because  it  has  not  been  definitely  settled  as 
yet  whether  these  bodies  are  absolutely  identical.  "  Nuclein  "  was  first  isolated  by 
Miescher^  from  the  nuclei  of  the  pus-corpuscles.  Somewhat  later  KosseP  demon- 
strated that  the  essential  constituents  of  this  body  are  the  purin  and  pyrimidin  sub- 
stances and  not  the  phosphorus.  That  this  is  true  may  be  gathered  from  the 
fact  that  the  yolk  of  the  unfertilized  egg  of  birds  contains  no  purin,  while  the 
developing  eggs  yield  large  amounts  of  this  substance.  Somewhat  later  Altmann* 
succeeded  in  abstracting  nucleic  acid  from  different  proteids.  This  constituent 
of  the  nucleoproteids  seems  to  be  present  in  rather  constant  quantities,  while  the 
albuminous  material  appears  to  fluctuate  considerably.  It  is  usually  combined 
with  a  basic  albuminous  substance,  forming  such  bodies  as  protamin  or  histon. 
The  isolation  of  these  components  of  the  nucleoproteid  is  easily  effected  in  most 
cases. 

Carbohydrates  are  not  found  as  free  primary  constituents  of  the  cell,  but  are 
contained  in  the  nucleic  acid  portion  of  the  nucleoproteids,  in  glycoproteids  and 
cerebrosides.     In  the  cells  of  the  liver  glycogen  in  held  as  a  reserve  foodstuff. 

Among  the  inorganic  substances  masked  iron  has  been  shown  to  exist  in  chro- 
matin.^ IjCss  convincing  results  have  been  obtained  pertaining  to  phosphorus. 
Protoplasm,  however,  contains  many  of  the  commonest  salts,  namely,  sodium, 
potassium,  magnesium,  calcium,  iron  (sulphates,  chlorids,  phosphates  and  carbon- 
ates), and  at  times  also  iodin,  manganese,  copper,  zinc,  barium  and  silicon.  The 
proportion  of  these  elements,  however,  differs  in  different  cells;  in  fact,  those  named 
last  should  be  regarded  merely  as  accidental  admixtures,  because  they  are  present 
only  under  special  conditions.  It  should  also  be  emphasized  that  these  inorganic 
substances  may  occur  either  independently  or  in  combination  with  the  organic 
material;  moreover,  they  should  not  be  considered  as  passive  constituents,  because 
they  play  an  important  part  in  the  production  of  all  vital  phenomena. 

Water  constitutes  about  three-fourths  of  living  substance,  the  remaining  portion 
of  it  being  composed  of  inorganic  and  organic  material.  In  some  instances,  in  fact, 
as  much  as  94  per  cent,  of  it  consists  of  water  and  the  common  salts.  For  this 
reason,  it  must  be  evident  that  the  specific  gravity  of  protoplasm  must  show  con- 
siderable variations,  although  it  may  be  said  that  its  average  value  is  about  1.025. 
This  value,  for  example,  holds  true  absolutely  in  the  case  of  paramecia  which 
Jensen^  subjected  to  different  known  concentrations  of  potassium  carbonate 
solutions.  It  is  conceivable,  however,  that  certain  cells,  and  especially  those 
containing  calcareous  admixtures,  exceed  this  value,  while  others,  possessing 
prominent  vacuoles,  may  fall  below  unity  and  be  buoyant. 

1  Kanitz,  in  Oppenheimer's  Handb.  der  Biochemie,  ii,  1910,  213. 

2  Histochem.  und  physiol.  Arbeiten,  ii,  3,  Leipzig,  1900. 

3  Zeitschr.  fur  physik.  Chemie,  x,  1866,  248. 

4  Ai'chiv  fiir  Anat.  und  Physiol.,  1889,  524. 

^  A.  B.  Maccallum,  Ergebnisse  der  Physiol.,  vii,  1908,  552. 

epfluger's  Archiv,  liv,  1893,  537;  also:  Lillie,  Journ.  of  MorphoL,  xii,  1896. 


LIVING    SUBSTANCE 


27 


The  Functional  Relation  of  the  Cytoplasm  and  Nucleus. — The 
importance  of  the  nucleus  to  the  cell  may  be  shown  by  depriving 
certain  parts  of  it  of  its  nuclear  material.  Thus,  Hofer/  divided 
ameba  in  such  a  manner  that  the  nucleus  came  to  lie  in  each  case  en- 
tirely in  one  of  the  fragments.  This  particular  fragment  regenerated 
very  quickly  into  a  complete  cell  showing  a  perfectly  normal  behavior, 
while  the  non-nucleated  portions  lost  their  power  of  movement  and 
ingestion  of  food  in  the  course  of  a  few  days  and  disintegrated.  This 
disintegration,  however,  could  be  prevented  if  at  least  a  small  frag- 
ment of  the  nucleus  was  apportioned  to  these  parts. 


y 


Fig.  3. — The  Functional  Relation  of  the  Cytoplasm  and  Nucleus. 
A.  An  ameba  divided   into  a  nucleated  and  non-nucleated  portion.     B.  The  same 
portion  after  an  interval  of  eight  days.      {After  Hofcr.) 

Quite  similarly,  it  was  found  that  denucleated  rhizopods  and 
radiolaria  are  able  to  move  and  to  ingest  nutritive  particles,  but  that 
the  digestion  of  the  latter  is  rarely  completed.  Furthermore,  Verworn^ 
has  shown  that  polystomella  which  possesses  the  power  of  secreting 
calcareous  material,  loses  this  function  soon  after  its  nucleus  has 
been  removed.  Plant  cells  behave  in  a  similar  way.  Thus,  Klebs^ 
has  proved  that  isolated  fragments  of  plant  protoplasm  are  quite 
unable  to  form  a  cellulose  membrane,  while  the  nucleated  fragments 
retain  this  faculty.  In  addition,  it  might  be  mentioned  that  the 
nucleus  is  situated  as  a  rule  in  that  area  of  the  cell  in  which  the  most 
active  growth  is  taking  place.  This  tendency  is  well  displayed  in  the 
root-hairs  of  plants,  in  which  the  nuclei  are  retained  at  their  very  tips 
during  the  development  of  these  appendages  and  are  then  made  to 

1  Jen.  Zeitschr.  fiir  Naturvv.,  1889. 

2  Pfluger's  Archiv,  li,   1891,  1. 

3  Biol.  ZentralbL,  1887. 


28 


GENERAL    PHYSIOLOGY 


retreat  into  the  deeper  layers.     Tliis  is  also  true  of  the  nuclei  of  many 
secretory  glands,  such  as  the  silk  glands  of  different  lepidoptera. 

The  nucleus,  therefore,  must  be  regarded  not  only  as  a  necessary 
constituent  of  the  cell,  but  as  its  most  important  constructive  ele- 
ment. To  be  sure,  many  cells,  such  as  the  erythrocytes  of  the  mam- 
malian blood,  are  capable  of  leading  an  independent  existence  even 
without  a  nucleus,  but  this  example  can  scarcely  be  used  as  a  proof 
against  the  preceding  statement,  because  these  cells  are  nucleated 
when  formed  and  do  not  possess  the  power  of  regeneration.  Even  the 
bacteria  form  only  an  apparent  exception,  because  their  nuclear 
material  is  either  mdely  disseminated  through  the  cell  in  the  form  of 
dust-like    granules    or   is    already    arranged    as    spores.     Obviously, 


Fig.  4. — Regexeratiox  of  Stextor  Roeselii. 
A.  Stentor  divided  into  two  nucleated  portions;  B  and  C  newly  formed  organisms. 
(Verworn .) 

therefore,  the  chemical  and  structural  development  of  the  cell  depends 
upon  the  nucleus.  To  some  extent,  however,  it  is  also  true  that  a 
nucleus  devoid  of  cytoplasm,  cannot  exist  as  a*n  independent  entity. 
To  be  sure,  in  many  cells  the  protoplasmic  envelope  is  extremely 
narrow  and  in  many  it  does  not  seem  to  be  present  at  all.  But,  the 
spermatozoa,  to  which  reference  is  now  had,  are  not  capable  of  trans- 
formation nor  of  multiphcation,  their  sole  purpose  being  to  unite 
with  the  ova.  Verworn,  moreover,  has  shown  that  the  isolated  nucleus 
of  the  large  radiolaria  does  not  long  survive  its  removal  from  the  cell. 
These  functional  differences  between  the  cytoplasm  and  the  nucleus 
are  associated  with  definite  chemical  differences.  This  may  be 
inferred  from  the  important  changes  which   the  nucleus   undergoes 


GENERAL    PHENOMENA    OF    LIFE  29 

(luring  the  division  of  tho  cell  by  the  process  of  karyokinesis  as  well 
us  from  its  peculiar  staining  reactions.  Thus,  we  find  that  the  growth 
and  activity  of  the  cell  is  accompanied  by  definite  variations  in  the 
size  and  appearance  of  the  chromatin  elements.  In  the  egg  of  the 
shark  they  are  small  at  first  and  stain  deeply,  while  later  on  they 
lose  their  staining  qualities  and  increase  in  mass.  At  maturity,  the 
chromosomes  again  become  smaller  and  finally  break  up  into  fine 
granular  bodies  possessing  an  intense  affinity  for  nuclear  dyes.  Re- 
garding the  chemical  differences  between  the  nucleus  and  the  cytoplasm, 
little  is  known.  The  proteins  of  living  substance  are  conjugated  in 
their  nature,  because  the  simple  proteins  are  here  combined  with 
other  complex  bodies.  They  present,  however,  certain  distinct 
differences  in  that  those  of  the  nucleus  form  the  class  of  the  nucleo- 
proteids,  while  those  of  the  cytoplasm  are  largely  compounds  of  protein 
and  lecithin.  The  former  are  characterized  by  their  content  in 
phosphorus  and  by  their  decomposition  products  of  nuclein  and  pro- 
tein. Nuclein  which  seems  to  be  the  chief  constituent  of  the  nuclei 
of  cells,  may  be  broken  down  into  nucleic  acid  and  protamine,  the  latter 
presenting  the  characteristics  of  a  protein  substance. 


CHAPTER  II 
GENERAL  PHENOMENA  OF  LIFE 

Growth  and  Metabolism. — ^Life  may  be  investigated  in  different 
ways.  To  begin  with,  the  inquiry  may  be  directed  along  chemical 
lines,  to  discover  not  only  the  material  entering  into  the  composition 
of  hving  matter,  but  also  the  changes  which  this  material  undergoes 
in  the  course  of  the  vital  processes.  Special  emphasis  should  in  this 
case  be  placed  upon  its  metabolism,  i.e.,  upon  the  changes  presented 
by  it  during  its  periods  of  assimilation  and  dissimilation.  In  the 
second  place,  life  may  be  investigated  by  physical  means,  at  which 
time  the  question  regarding  the  energetics  of  protoplasm  must  be 
most  carefully  considered.  Living  matter  has  been  found  to  produce 
energy  in  the  form  of  mechanical  energy,  heat,  light  and  electricity. 
In  the  third  place,  it  is  possible  to  study  either  its  gross  or  minute 
structure,  i.e.,  to  pay  special  attention  to  the  form  in  which  it  exists, 
but  naturally,  life  does  not  present  itseK  exclusively  in  any  one  of  these 
ways,  but  as  a  homogeneous  whole.  These  methods,  therefore,  are 
<5mployed  merely  for  the  purpose  of  analyzing  this  process  from  differ- 
ent standpoints.     One  amplifies  the  other. 

Living  substance  is  always  in  activity.  It  grows;  it  secretes;  it 
moves  from  place  to  place  and  naturally,  all  these  processes  require  work 
and  the  production  of  energy  which  is  derived  from  the  union  of  its  dif- 


30  GENERAL    PHYSIOLOGY 

f  erent  constituents  with  oxygen.  Obviously,  this  constant  Uberation  of 
energy  in  its  various  forms,  must  be  compensated  for,  i.e.,  hving  sub- 
stance must  either  generate  it  or  obtain  it  from  some  outside  source. 
The  law  of  the  conservation  of  energy,  however,  teaches  us  that  energy 
is  not  created  but  is  merely  transformed  from  one  kind  into  another 
and  hence,  living  matter  must  derive  it  from  somewhere,  namely,  from 
the  medium  in  which  it  lives.  Various  substances  are  here  at  hand 
which  contain  stored  or  potential  energy.  When  assimilated  by  liv- 
ing matter,  either  through  its  respiratory  or  digestive  channel,  these 
chemical  bodies  are  converted  into  kinetic  energy. 

The  metabolism  of  a  cell  consists  in  a  continuous  decomposition 
and  new  formation  of  its  protoplasmic  material.  The  former  process 
is  designated  as  dissimilation  or  catabohsm,  and  the  latter  as  assimila- 
tion or  anabolism.  It  is  true,  however,  that  the  metabolism  is  uniform 
only  in  principle,  because  practically  every  type  of  cell  has  its  own 
pecuHar  work  to  perform  and  hence,  a  number  of  special  varieties  of 
metabolism  are  obtained.  Expressed  in  another  way,  it  may  be  said 
that  the  fundamental  interchange  of  material  between  the  cell  and  its 
surroundings  is  modified  in  manj^  cases  to  suit  particular  purposes. 
Thus,  a  certain  group  of  cells  may  be  destined  to  give  rise  to  a  digestive 
secretion,  while  another  furnishes  chiefly  contractile  reactions,  and  so 
on.  This  specificity,  however,  is  not  so  clearly  marked  in  free-living 
unicellular  organisms  as  it  is  in  the  more  complex  animals  and  plants, 
because  the  function  of  the  former  is  not  so  diversified. 

The  catabohc  processes  occurring  in  a  cell  necessitate  a  constant 
acquisition  of  new  material  to  replenish  that  which  has  been  lost. 
It  is  true,  however,  that  the  manner  in  which  this  assimilation  is  ac- 
complished, differs  somewhat  in  different  animals  and  plants.  An 
especially  tedious  process  is  in  existence  in  the  green  plants,  because 
their  protoplasm  is  built  up  from  the  simplest  possible  compounds, 
such  as  carbon  dioxid,  water  and  various  inorganic  salts.  The  animal 
cell,  on  the  other  hand,  is  constituted  differently  so  that  it  can  also 
make  use  of  the  more  complex  foods  held  in  the  form  of  organic  com- 
binations. It  must  be  evident,  however,  that  the  former  can  no  longer 
be  regarded  as  synthetic  and  the  latter  as  decomposition  organisms, 
because  the  metabolism  of  both  types  of  cells  is  dependent  upon  proc- 
esses of  dissociation  and  synthesis.  It  is  true,  however,  that  the  life 
of  the  animals  depends  upon  that  of  the  plants,  because  only  the  latter 
are  capable  of  producing  carbohydrates,  fats  and  proteids  from  inor- 
ganic material.  These  are  the  essentials  of  animal  life.  Animals, 
therefore,  are  the  parasites  of  the  plants.  There  is,  however,  one  ex- 
ception to  this  rule,  because  those  plants  which  contain  no  chlorophyl, 
such  as  the  fungi,  must  make  use  of  organic  substances  in  order  to 
obtain  their  requirement  in  carbon.  The  fungi,  however,  are  capable 
of  forming  nitrogen  from  the  inorganic  constitutents  of  the  soil,  while 
animals  must  derive  their  supply  of  nitrogen  exclusively  from  proteids 
and  derivative  compounds.     As  far  as  their  metabolism  is  concerned, 


GENERAL    PHENOMENA    OF    LIFE  31 

the  fungi  and  allied  plants  form,  therefore,  an  intermediate  group 
between  the  gre(>n  i)lants  and  the  animals,  i.e.,  between  those  (uitities 
of  living  sul)slaiu'(^  whieh  assimilate  the  carbon  from  carbon  dioxid 
under  the  influence  of  the  rays  of  the  sun  and  those  which  dciive  their 
energetics  from  foodstuffs. 

Assiniilation  implies  that  the  organisms  must  ingest  nutritive 
material  which,  after  its  digestion,  is  absorbed  and  utilized.  The 
manner  in  which  this  ingestion  is  accomplished  differs  materially  with 
the  general  form  and  behavior  of  the  organisms.  In  the  case  of  free- 
Hving  and  naked  unicellular  masses,  the  acquisition  of  the  nutritive 
substances  takes  place  apparently  at  any  point  of  the  surface  by  the 
process  of  engolfing,  while  in  the  more  specialized  organisms,  it  occurs 
in  a  particular  place,  namely  at  the  gullet.  The  reduction  or  digestion 
of  the  food  is  then  effected  by  means  of  enzymes  contained  in  secre- 
tions which  hydrolyze  it  and  render  it  di-alyzablc  and  assimilable. 
But  while  many  cells  possess  the  power  of  digesting  the  foodstuffs 
themselves,  many  do  not.  The  latter,  therefore,  require  already 
prepared  food.  In  the  higher  forms  this  preparation  is  effected  by 
special  groups  of  cells  forming  the  digestive  organs.  For  this  reason, 
we  speak  of  intracellular  and  extracellular  digestion. 

The  phenomena  of  dissimilation  are  ushered  in  by  the  decomposi- 
tion of  the  protoplasm,  in  consequence  of  which  the  various  forms  of 
energy  are  then  liberated.  It  is  necessary,  however,  to  form  the  ma- 
terial lost  anew,  otherwise  the  catabolism  might  progress  beyond  a 
certain  limit  and  endanger  the  life  of  the  cell.  Clearly,  oxygen  is  a 
necessary  factor  in  this  reduction,  at  least  in  most  organisms,  but  it 
has  not  been  definitely  settled  as  yet  whether  it  forms  a  true  anabolic 
product  of  the  cell  in  the  shape  of  "intramolecular"  oxygen,  or  whether 
it  is  present  in  the  surrounding  medium  in  its  molecular  form  to  be 
made  use  of  as  such  whenever  required.  As  a  result  of  this  oxida- 
tion, the  cell  gives  rise  to  a  number  of  products  which  are  of  no  further 
use  to  it  and  are  later  on  gotten  rid  of  by  the  process  of  excretion. 
These  waste  materials  are  of  many  kinds.  Chief  among  them  are  those 
arising  from  carbon  and  hydrogen,  namely  carbon  dioxid  and  water. 
A  number  of  them  are  derived  from  the  proteids,  for  example,  urea, 
uric  acid,  hippuric  acid,  creatin,  etc.,  which  are  either  suspended  or 
dissolved  in  water.  Their  complete  reduction  frequently  requires 
special  agents  which  are  brought  to  bear  upon  them  through  the  media 
of  the  excretions. 

The  purpose  of  metabolism  is  to  keep  the  cells  in  a  physiological 
condition,  as  evinced  by  the  amount  of  energy  liberated  by  them. 
The  cell,  therefore,  is  the  seat  of  life.  It  receives  certain  substances 
and  with  them  a  definite  amount  of  potential  energy  which  is  then 
transformed  into  kinetic  energy  in  its  various  forms.  Thus,  cells  are 
destined  to  produce  work,  either  directly  or  indirectly.  The  green 
plants,  for  example,  may  be  regarded  very  largely  as  potential  factors, 
because  their  energy  must  first  be  produced  in  the  presence  of  sunlight. 


32  GENERAL    PHYSIOLOGY 

To  begin  with,  the  substances  consumed  by  them,  possess  no  potential 
energy,  but  light,  in  connection  with  their  content  in  chloi-ophyl,  gives 
rise  to  a  splitting  of  the  molecules  of  the  carbon  dioxid  and  water  so 
that  the  resulting  atoms  of  carbon,  hydrogen  and  oxygen  are  at  liberty 
to  enter  other  chemical  combinations.  In  this  way,  a  number  of  com- 
plex substances  are  produced,  representing  a  large  store  of  potential 
energy,  which  is  made  use  of  later  on  by  the  animal  cell.  It  is  true, 
however,  that  this  assimilation  and  synthesis  is  associated  with  dis- 
similation, in  the  course  of  which  the  plant  gives  rise  to  waste  products 
and  generates  certain  forms  of  energy,  such  as  motion,  heat,  light,  and 
osmotic  power.  It  is  quite  apparent,  however,  that  in  the  case  of  the 
plants  the  kinetic  energy  is  rather  subordinate  to  the  potential — a  rela- 
tionship which  is  reversed  in  the  animal. 

The  energetics  of  a  cell  present  themselves  in  various  forms  which, 
as  we  have  just  seen,  may  be  grouped  as  resting  or  potential  energy 
and  as  moving  or  kinetic  energy.  Among  the  former  we  have  chemical, 
osmotic,  cohesion  and  gravitation  forces,  and  among  the  latter  mechan- 
ical power,  heat,  light  and  electricity.  But  naturally,  this  classi- 
fication is  not  fixed,  because  some  of  these  energies  may  present  them- 
selves in  either  form.  The  chemical  energy,  for  example,  remains 
potential  only  as  long  as  the  atoms  retain  their  position  toward  one 
another  and  becomes  kinetic  as  soon  as  they  rearrange  themselves  in 
accordance  with  their  specific  affinities.  Thus,  the  animal  receives 
potential  chemical  energy  in  the  shape  of  complex  organic  substances 
and  as  oxygen.  The  regrouping  of  the  former  under  the  influence 
of  oxygen  eventually  gives  rise  to  carbon  dioxid,  water  and  simpler 
nitrogenous  bodies  as  well  as  to  a  large  amount  of  actual  energy. 
Metabolism,  therefore,  is  intended  to  keep  the  organism  in  energy- 
equilibrium.  The  chemical  intake  and  outgo  are  balanced  in  such 
a  way  that  the  cells  can  continue  to  furnish  the  energy  required  of 
them.  The  metabolic  equilibrium  and  the  dynamical  equilibrium 
must  in  the  long  run  pursue  a  parallel  course. 

Living  substance  presents  itself  in  many  characteristic  forms,  the 
study  of  which  has  always  been  apportioned  to  morphology.  It  is 
true,  however,  that  a  hard  and  fast  line  between  the  structural  and 
functional  aspect  of  living  matter  cannot  be  drawn,  because  the  former 
changes  constantly  under  the  influence  of  different  physiological 
conditions.  An  organism  is  always  in  activity  and  conditions  within 
it  are  never  at  a  standstill,  although  in  many  cases  these  processes 
may  be  either  very  slow  or  too  minute  to  be  immediately  apparent. 
Thus,  the  metabolic  changes  are  balanced  in  such  a  way  that  the 
losses  suffered  in  consequence  of  dissimilation  are  always  made  up, 
allowing  the  cell  to  increase  its  substance  and  to  grow.  Growth  is 
the  simplest  manifestation  of  organic  progress.  In  the  second  place, 
living  substance  in  any  form  is  capable  of  reproducing  its  like  so  that 
its  continuance  is  assured  as  long  as  conditions  favorable  for  its  exist- 
ence prevail.     If  the  environment  changes,  living  substance  possesses 


GENERAL    PHENOMENA    OF    LIFE  33 

the  power  of  adapting  itself  to  the  new  conditions,  provided,  of  course, 
that  the  change  to  which  it  is  subjected,  is  not  extreme.  Hence,  our 
conception  of  Hfc  is  Uniited  to  such  phenomena  as  mctabohsm,  growth 
and  evolution,  reproduction,  irritability  and  contractility,  inclusive 
of  motion. 

General  Conditions  of  Life. — The  reason  for  the  great  diversity  in 
the  form  of  living  matter  must  be  sought  in  the  conditions  under  which 
it  is  made  to  exist.  Any  change  in  the  latter  vaiios  its  metabolism, 
shape  and  energetics,  but  naturally,  it  would  lead  us  altogether  too 
far  to  study  the  different  aspects  of  life  in  detail.  In  general,  however, 
it  may  be  stated  that  living  matter  presents  certain  internal  as  well  as 
external  characteristics.  Among  the  former  might  be  mentioned  its 
structure,  composition  and  physical  properties,  the  study  of  which 
would  necessitate  an  analysis  of  the  cell  and  its  component  (dements. 
Among  the  latter  are  to  be  noted  the  different  conditions  under  which 
the  cell  is  made  to  live,  inclusive  of  the  character  of  the  medium,  the 
temperature,  the  atmospheric  pressure,  osmotic  pressure,  moisture, 
and  store  of  nutritive  material. 

As  long  as  these  conditions  remain  the  same,  life  is  said  to  be  spon- 
taneous. This  term,  however,  is  not  a  very  good  one,  because  life 
is  never  actually  unconditioned.  Thus,  an  organism  leading  appa- 
rently a  perfectly  spontaneous  existence,  is  constantly  under  the  in- 
fluence of  internal  and  external  conditions.  Its  spontaneity,  therefore, 
is  only  apparent,  owing  to  the  fact  that  the  influences  acting  upon  it 
are  normal  in  their  character  and  remain  constant  in  their  intensity. 
On  the  other  hand,  if  the  latter  suddenly  assume  a  different  quality  or 
become  augmented  by  new  conditions,  the  spontaneity  immediately 
gives  way  to  phenomena  of  stimulation.  Hence  a  stimulation  must 
result  whenever  the  conditions  of  life  are  suddenly  and  markedly  al- 
tered. In  view  of  the  fact  that  the  latter  are  very  numerous  and 
relatively  inconstant,  the  possibility  of  stimulation  is  always  present, 
provided  the  protoplasm  retains  its  receptive  power. 

Upon  this  basis,  a  stimulus  may  be  defined  as  any  extraordinary 
change  in  the  conditions  to  which  an  organism  may  be  subjected. 
^Vhile  the  number  of  stimuli  is  practically  unlimited,  it  is  possible  to 
arrange  them  qualitatively  in  the  following  manner: 

(a)  Mechanical  stimuli,  inclusive  of  such  influences  as  touch,  pressure,  stroking, 
pulling,  the  effects  of  gravitation,  cohesion  and  adhesion,  etc. 

(b)  Chemical  stimuli,  produced  by  various  normal  and  abnormal  substances. 
Among  the  former  may  be  included  the  nutritive  substances  ordinarily  required  by 
living  matter,  and  among  the  latter,  practically  any  chemical  agent  with  which  it  is 
accidentally   brought   into    contact. 

(c)  Osmotic  stimuli,  consisting  in  changes  in  the  osmotic  pressure  of  the  sur- 
rounding medium.  As  these  alterations  are  commonly  associated  \vith  chemical 
reactions,  they  are  frequently  included  among  the  former. 

(d)  Thermal  stimuli,  produced  by  variations  in  the  temperature  of  the  medium. 

(e)  Photic  or  radiating  stimuli,  caused  by  changes  in  the  intensity  and  qualit}'' 
of  the  light.     Under  this  heading  may  also  be  placed  the  peculiar  rays  discovered 

3 


34  GENERAL    PHYSIOLOGY 

in  more  recent  years  by  Hertz  and  Rontgen,  and  those  emitted  by  uranium  and 
radium. 

(/)  Electrical  stimuli,  produced  by  the  exposure  of  the  organism  to  the  electri- 
cal current.  Magnetic  stimuli  are  no  longer  recognized,  because  it  seems  that 
living  substance  cannot  be  influenced  by  magnets. 

Besides  the  quality  of  the  stimulus,  we  must  also  take  into  account 
its  "strength, "  this  term  being  employed  at  this  time  in  a  quantitative 
way  to  characterize  the  sum  total  of  its  intensity,  duration  and  fre- 
quency. Every  organism  is  constantly  under  the  influence  of  stimuli 
of  all  sorts  which,  as  long  as  they  retain  a  normal  intensity,  give  rise 
to  normal  reactions.  The  conditions  prevailing  at  this  time,  may 
be  said  to  be  optimum  in  their  character.  Living  substance  reacts 
toward  these  in  the  best  possible  manner.  But,  stimuU  may  also  be- 
come excessive,  and  force  the  living  substance  to  react  maximally.  It 
is  only  natural  to  assume  that  a  continued  maximal  activity  must  finally 
produce  injurious  effects.  Lastly,  stimuli  may  possess  so  shght  an 
intensity  that  they  fail  absolutely  in  producing  an  effect.  Minimal 
stimuli,  and  especially  subminimal  stimuli,  must  eventually  prove  as 
dangerous  to  life  as  maximal  ones. 


A  ■-  A      P 


X> 


Fig.  5. — Intensity  of  Stimulation. 
L,  life;  D,  death;  SMi,  subminimal;  Mi,  minimal;  0,  optimum;  M,  maximal;  SM, 
supramaximal  stimuli;  T,  threshold. 

It  appears,  therefore,  that  life  is  possible  only  between  these 
two  extremes  and  that  death  must  result  whenever  this  realm  is 
exceeded  in  either  direction.  To  begin  with,  therefore,  living  matter 
may  be  subjected  to  the  subminimal  stimuli  toward  which  it  does 
not  react  at  all,  at  least  not  visibly.  Eventually,  however,  a  strength 
of  stimulus  will  be  reached  toward  which  it  reacts  just  barely.  At 
the  point  where  these  minimal  reactions  just  begin  to  appear  lies 
the  threshold  of  stimulation.  If  the  strength  of  the  stimulus  is  now 
increased  still  further,  a  point  will  be  reached  at  which  the  reactions 
become  maximal  and  finally,  a  point  at  which  they  show  a  supra- 
maximal character. 

It  should  be  emphasized,  however,  that  the  preceding  outline  can- 
not be  applied  rigidly  in  all  cases,  because  living  substance  exhibits 
certain  differences  in  its  behavior  which  are  dependent  upon  differ- 
ences in  its  chemical  and  physical  constitution.  Thus,  optimum 
conditions  are  not  always  found  midway  between  the  minimal  and 
maximal  extremes,  and  neither  does  a  certain  kind  of  maximal  stimulus 
invariably  cause  fatigue  or  death.  It  is  a  matter  of  common  observa- 
tion that  the  energy  contained  in  a  stimulus  is  always  very  much 
smaller  than  the  subsequent  production  of  kinetic  energy.  To  some 
extent   living   substance  also  possesses  the  power  of  adapting  itself 


GENERAL    PHENOMENA    OF    LIFE  35 

to  stimuli.  Thus,  while  a  certain  stimulus  may  at  first  produce  a 
maximal  reaction,  it  often  loses  its  stimulating  qualities  altogether 
in  the  course  of  time.  This  state  of  adaptation  should  be  sharply 
differentiated  from  a  somewhat  similar  one  which  is  known  as  the 
refractory  state.  It  has  been  previously  emphasized  that  every 
activity  of  protoplasm  incurs  a  certain  destruction  of  material  which 
must  first  be  overcome  by  assimilation  before  another  reaction  can 
take  place.  Thus,  if  the  dissimilation  has  been  severe,  or  if  the  as- 
similation has  been  hindered  in  some  way,  tiie  living  substance  sud- 
denly finds  itself  unable  to  receive  stimuli,  or  to  develop  them  into  a 
reaction.  This  period  during  which  living  matter  remains,  so  to  speak, 
impermeable  to  stimuli,  is  known  as  the  refractory  period. 

The  property  of  protoplasm  to  receive  stimuli  and  to  undergo  in 
consequence  of  them  characteristic  chemical  and  physical  changes,  is 
known  as  irritability.  Most  generally,  however,  these  alterations  are 
not  confined  to  the  seat  of  the  excitation  but  are  propagated  to  other 
parts  of  its  mass.  This  transmission  of  the  waves  of  irritability  is 
dependent  upon  its  property  of  conductivity.  In  the  multicellular 
forms,  conduction  between  widely  separated  parts  is  greatly  facilitated 
by  the  interposition  of  nervous  tissue  which  is  peculiarly  suited  for 
this  function.  The  impulses  leave  these  conducting  paths  eventually 
to  be  transferred  to  the  constituents  of  the  motor  organ.  The  recep- 
tion of  an  impulse  by  the  cell  is  usually  followed  by  the  shifting  of  its 
constituents  which  in  turn  leads  to  a  change  in  its  form  and  position. 
This  behavior  of  hving  matter  is  dependent  upon  its  property  of 
contractility. 


SECTION    II 
PHYSIOLOGY  OF  MUSCLE  AND  NERVE 


CHAPTER  III 
MOTION 

Different  Types  of  Motion. — The  phenomenon  of  contractiHty 
consists  in  a  shifting  about  of  the  constituents  of  the  cell.  It  may 
be  perfectly  local  or  more  far  reaching,  leading  finally  to  changes  in 
the  shape  and  position  of  the  organism  as  a  whole.  In  this  waj',  this 
liberation  of  energy  gives  rise  to  motion  and  locomotion,  phenomena 
which  the  laAanan  regards  as  the  most  certain  proofs  of  Ufe.  The 
character  of  these  movements  is  veiy  manifold  and  is  in  keeping 
with  the  general  structure  and  arrangement  of  the  motor  organs  pro- 
ducing them.  In  general,  it  may  be  said  that  motion  may  be  accom- 
plished either  passively  or  actively,  in  consequence  of  the  following 
processes:^ 


A.  Passive 


Motion 


B.  Active 


Swelling  of  the  cell  wall 

Changes  in  the  cell-turgor 

Changes  in  the  specific  gravity 
1  Secretion 
I  Growth  f  ameboid 

^  Contraction  and  expansion  i  ciliary 

I  muscular 

A  passive  motion  results  whenever  the  power  to  move  is  not  inherent  in  the 
object.  Thus,  if  we  observe  the  circulation  of  the  blood  under  the  microscope,  the 
erythrocytes  are  seen  to  traverse  the  vascular  channels  with  a  certain  speed,  but 
this  movement  is  imparted  to  them  by  an  outside  force  residentin  the  musculature 
of  the  heart.  We  may  also  study  the  streaming  of  theprotoplasm  in  such  organ- 
isms as  the  rhizopods.  We  note  here  the  slow  progression  of  the  granules  to  and 
from  the  cells,  but  they  themselves  are  quite  inactive  and  move  solely  in  conse- 
quence of  the  flow  of  the  medium  in  which  they  are  contained.  In  this  connection, 
mention  should  also  be  made  of  the  so-called  Brownian  molecular  motion  which  is 
displayed  b.y  many  plant  cells,  and  lower  organisms.  A  verj'  favorable  object 
for  observ'ation  is  the  unicellular  green  alga,  called  closterium  (Fig.  6,  I)  which 
contains  in  each  end  of  its  crescent-shaped  body  a  vacuole  filled  with  fluid  and  fine 
granules  (iv).  If  the  latter  are  observed  under  the  high  power  of  a  microscope, 
they  are  seen  to  be  engaged  in  an  incessant  trembUng  motion.     The  same  pheno- 

1  Verworn's  Allg.  Physiol.,  Jena,  1909,  and  Winterstein's  Handb.  der  allg. 
Physiol.,  Jena,  1912. 

36 


MOTION 


37 


mcnon  may  be  studied  in  the  so-called  salivary  corpuscles  (Fig.  6,  II)  which  are 
dead  leukocytes  that  have  entered  the  saliva  and  have  absorlied  much  water.  The 
delicate  molecular  movement  is  displayed  in  this  case  hy  the  fine  sranules  situated 
in  the  immediate  vicinity  of  the  nucleus.  Brown,  who  discovered  this  phenome- 
non in  the  cells  of  plants  (1827),  attributed  it  to  the  vibration  of  the  molecules 
themselves  and  regarded  it  therefore  as 
active.  Wiener  and  Exner,  however, 
have  proved  that  it  is  passive,  and  that  it 
represents  an  instability  similar  to  that 
exhibited  by  the  molecules  of  any  liquid. 
The  latter  are  never  at  a  standstill,  but 
always  change  their  position  and  con- 
stantly move  toward  and  away  from  one 
another. 

Movements  by  swelling  of  the  cell -walls 
are  produced  whenever  the  constituents 
of  a  dry,  expansible  body  are  brought  into 
a  moist  medium  so  that  they  can  attract 
molecules  of  water.  The  latter  are  stored 
in  between  them  and  force  them  apart 
until  the  body  as  a  whole  increases 
markedly  in  volume.  As  an  example  of 
this  type  of  motion  might  be  mentioned 
the  so-called  resurrection-plants  found  in 
desert  regions.    These  plants  may  remain 

in  a  perfectly  dried  up  condition  for  several  years,  their  leaves  being  folded  to- 
gether like  the  fingers  of  a  closed  hand.  When  brought  into  a  moist  environ- 
ment, they  immediately  unfold  and  assume  definite  shape. 

Movements  by  changes  in  the  cell-turgor  are  observed  chiefly  in  plants.  In- 
side the  walls  of  the  different  cells  is  found  a  delicate  protoplasmic  sac,  formed  by 
the  so-called  primordial  utricle.     The  latter  is  filled  with  a  liquid,  the  cell-sap,  the 


U 

Fig.  6. — Brownian  Motion. 
Closterium;   with  vacuole.     II.   Sali- 
vary  corpuscle.     {Verworn.) 


A  B 

Fig.   7. — Sensitive  Plant  (Mimosa  pudica).      {Verworn  after  Detmer.) 
A.   Resting  position.     B.  Stimulated. 


concentration  of  which  is  varied  by  the  addition  of  certain  chemical  substances 
which  are  formed  in  the  course  of  the  vital  activities  of  these  cells.  As  a  result 
of  the  osmotic  influx  of  water,  the  pressure  in  the  primordial  sac  is  increased.  If 
the  concentration  of  the  medium  is  increased,  water  is  abstracted  from  the  cell. 
Variations  in  the  pressure  of  the  cell-sap  may  also  be  brought  about  by  the  con- 
traction of  the  primordial  utricle.     Of  greatest  importance  at  this  time,  is  the 


38 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


fact  that  the  tension  or  turgor  existing  in  the  sap-sac  is  brought  to  bear  upon  the 
elastic  wall  of  the  cell  with  the  result  that  the  size  of  the  latter  is  either  increased 
or  diminished.  In  many  plants  these  changes  in  the  turgescence  occur  very  sud- 
denly and  either  spontaneously  or  in  consequence  of  a  stimulus  of  some  kind.  As 
an  example  of  this  type  of  motion  might  be  mentioned  the  folding  up  and  drooping 
of  the  leaflets  of  the  sensitive  plants  (mimosa  pudica),  when  touched  or  when  ex- 
posed to  low  intensities  of  light.  Sunlight,  on  the  other  hand,  causes  them  to 
unfold  and  to  erect  their  stems  and  leaflets.  A  similar  phenomenon  is  exhibited 
by  the  insect-catching  flowers  of  the  carnivorous  plants. 

Movements  by  changes  in  the  specific  gravity  may  be  observed  in  certain 
radiolaria.  Ordinarily  these  organisms  are  heavier  than  water  and  creep  along 
the  bottom  of  stagnant  pools.  They  are  capable,  however,  of  rising  to  the  surface 
by  generating  small  bubbles  of  carbon  dioxid  which  are  deposited  among  their 

protoplasmic  streamers.     At  the  surface  this  gas 
t  is  quickly  discharged.     In  consequence  of  the  in- 

^       I         ^  crease  in  their  specific  gravity  then  resulting  they 

again  sink  to  the  bottom. 

Movements  by  secretion  result  in  algse  and 
oscillarige  and  are  produced  by  the  projection  from 
their  bodies  of  a  sticky  liquid  which  adheres  to 
the  surface  of  the  receptacle.  As  a  result  of  this 
secretion  the  body  of  the  organism  is  slowly  forced 
forward  in  a  definite  direction. 

Movements  by  growth  are  very  general  and 
occur  whenever  a  cell  increases  its  mass.  But  as 
the  ordinary  processes  of  assimilation  are  slow, 
the  detection  of  this  movement  often  necessitates 
a  comparison  of  conditions  at  different  periods  of 
the  life  of  the  organism.  Many  seedlings  display 
a  more  perceptible  growth.  Moreover,  many 
seeds  and  fruits  require  only  the  slightest  touch 
to  make  them  burst  and  to  discharge  their  con- 
tents. In  these  cases  the  mechanical  energy  de- 
veloped by  growth  has  been  stored,  and  has  placed 
the  capsular  investment  under  a  high  degree  of 
tension. 

The  alternate  contraction  and  expansion  of  a 
mass  of  protoplasm  means  that  it  assumes  a 
rounded  shape  during  the  former  phase  and  a 
flat  outline  during  the  latter.  Its  surface,  there- 
fore, undergoes  constant  changes,  but  naturally, 
only  those  organisms  can  display  this  phenomenon 
in  a  plastic  manner  which  possess  a  liquid  consistency.  We  have  previously  seen 
that  this  characteristic  is  universal  among  living  substance,  but  whether  an  organ- 
ism as  a  whole  is  motile,  depends,  of  course,  upon  the  character  of  its  framework 
which  may  or  may  not  be  sufficiently  yielding  to  permit  the  contraction  of  its 
protoplasm.  Three  types  of  structures  are  evidently  well  adapted  for  this  pur- 
pose, namely,  {a)  small  masses  of  living  substance  which  are  not  surrounded  by  a 
distinct  cell  wall,  (6)  hair-like  protoplasmic  processes  with  which  many  cells  are 
beset,  and  (c)  the  muscle  cell  as  it  appears  in  striated,  non-striated  and  cardiac 
tissue. 

Ameboid  Movement. — When  placed  upon  a  slide  under  the  micro- 
scope, an  ameba-cell  appears  as  a  gray  droplet  embracing  a  nucleus 
and  contracting  vacuole.  Its  central  portion,  consisting  of  endoplasm, 
contains  as  a  rule  a  number  of  granules,  while  its  peripheral  zone,  or 
exoplasm,  is  more  or  less  hyaline.     When  kept  under  optimum  condi- 


\!:^ 


Fig, 


. DiATOMAE, 

Showing  Protrusion   of   Mu- 
cous Material.      (Verworn.) 


MOTION 


39 


tions,  this  droplet  of  living  substance  sends  out  lobate  processes  into 
the  surrounding  nicdiuni  which  are  constantly  increased  in  size  and 
length.  These  feelers,  or  pseudopodia,  may  be  sent  out  in  all  direc- 
tions, or  may  be  restricted  to  one  particular  locahty.  In  the  latter 
case,  the  entire  mass  of  the  cell  may  eventually  be  transferred  into 
one  of  these  projections,  occasioning  in  this  way  a  slow  onward  streaming 
of  the  protoplasm  and  its  admixtures.  This  centrifugal  movement, 
however,  may  be  changed  at  any  moment  into  a  centripetal  one  by 
stimulation.  The  cell  then  assumes  a  nearly  spherical  outline,  repre- 
senting the  state  of  contraction. 

This  type  of  movement  is  not  confined  to  the  ameba,  but  is  also 
exhibited  by  the  rhizopods,  the  egg  cells  of  certain  animals,  pigment 
and  giant  cells  and  the  leukocytes  of  the  blood.     In  the  leukocytes  it 


FiQ.  9. — An  Ameba,  Showing  Different  Stages  of  Movement.     (Verworn.) 

serves  the  primary  purpose  of  engulfing  nutritive  particles,  so  that 
these  may  be  digested  and  assimilated  by  the  Hving  substance.  It 
is  also  made  use  of  in  ridding  the  body  of  toxic  materials  of  all  sorts, 
this  process  having  been  designated  by  IVIetchnikoff  as  phago- 
cytosis. In  the  plant  cells  in  which  this  protoplasmic  streaming  is  very 
general,  it  serves  the  additional  purpose  of  disseminating  the  food 
substances. 

Ciliary  Movement.^ — CiHa  are  cellular  appendages  possessing  the 
shape  of  slender,  tapering  hairs.  Their  length  varies  greatly  in  dif- 
ferent animals.  In  the  trachea  of  man,  for  example,  they  measure 
0.003-0.005  mm.  in  length  and  0.0003  mm.  in  thickness.  Their  num- 
ber also  varies.  Some  of  the  infusoria,  such  as  paramecium,  are  beset 
with  several  thousands  of  them,  while  an  ordinary  lining  cell  of  the 
digestive  or  respiratory  passage  may  possess  only  several  hundreds  of 

1  Engelmann,  in  Hermann's  Handb.  der  Physiol.,  1879,  i,  380;  Putter,  Ergebn. 
der  Physiol,  i,  1903,  and  Verworn,  Allg.  Physiol.,  Jena,  1910. 


40 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


them.  While  their  number  is  generally  proportional  to  the  size  of  the 
cell,  it  may  also  happen  that  a  single  cell  is  equipped  with  only  one 
or  several  cilia.  When  especially  long  and  thick,  they  are  known 
as  flagellae.  In  the  protozoa,  these  cihated  cells  usually  extend  over 
the  entire  surface,  while  in  the  metazoa  they  occupy  more  restricted 
regions  of  the  body.  They  are  found,  for  example,  (a)  upon  the  ova 
and  embryos  of  many  invertebrates,  fish,  and  amphibia,  (6)  upon  the 
epidermis  and  in  the  digestive  tract  of  the  coelenterates,  worms,  echino- 
derms,  and  molluscs,  (c)  in  the  respiratory  passage  of  molluscs, 
amphibia,  fish,  birds  and  mammals,  and  (d)  in  the  urogenital  tract 
of  vertebrates.  In  man,  they  are  in  evidence  upon  the  mucous  mem- 
brane of  the  nose,  lacrimal  duct  and  sac,  Eustachian  tube  and  tym- 
panic cavity,  upper  portion  of  the  pharynx,  larynx  with  the  exception 


Fig.  10. — Ciliated  Cells. 
A,  from  a  liver  duct  of  the  garden 
snail;  B,  from  mucosa  of  frog.     {After 
M.  Haidenhain.) 


Fig.   11. —  Movement    of 
A  Single  Ilium. 
-•1,  Progressive  in  direction  of  arrow; 
B,  Regressive.     {After  Verworn.) 


of  the  vocal  cords,  trachea  and  bronchi,  uterus.  Fallopian  tube,  vagina, 
central  canal  of  the  spinal  cord  and  the  cerebral  ventricles.  During 
embryonal  life  ciliated  epithelium  is  also  present  in  the  mouth,  esoph- 
agus and  stomach 

The  phenomenon  of  ciliary  motion  is  brought  about  by  a  peculiar 
to  and  fro  movement  of  these  projections.^  Being  firmly  anchored  in 
the  outer  portions  of  the  cells,  they  swing  like  pendula  along  parallel 
planes  and  thus  avoid  striking  one  another.  In  many  cases,  however, 
the  planes  in  which  they  move  are  not  straight,  but  curved,  similating 
circles,  ovals,  or  even  the  course  of  a  whip-lash.  The  latter  is  espe- 
cially true  of  the  flagellse  with  which,  for  example,  sperm  cells  are  beset. 
Moreover,  if  our  attention  is  directed  to  a  single  row  of  cilia,  it  is 
noted  that  this  movement  is  progressive  in  character,  beginning  with 
their  position  of  rest.  The  latter  may  be  determined  most  easily 
by  rendering  them  inactive  by  means  of  a  narcotizing  agent.     At  this 

^  Erhart,  Studien  iiber  Flimmerzellen,  Archiv  fiir  Zellforschung,  xxxi,  1910. 


MOTION  41 

time,  the  different  cilia  do  not  project  vertically  outward,  but  are 
more  or  less  bent.  When  contracting  the  cilium  curves  strongly  toward 
its  vertical  position,  its  convex  border  being  at  first  strongly  inclined 
in  this  direction.  Having  reached  its  extreme  position  on  the  other 
side  of  the  vertical  line,  it  returns  to  the  position  of  rest  by  the  process 
of  relaxation.  The  former  movement  is,  of  course,  more  rapid  than 
the  latter  and  constitutes  the  effective  stroke  of  the  cilium.  It  is 
accomphshed  by  the  contraction  of  the  ciliary  substance  situated  on 
the  side  toward  which  the  stroke  is  being  directed,  the  opposite  side 
meanwhile  being  put  on  the  stretch.  The  contraction  having  been 
completed,  the  cilium  is  forced  into  its  original  position  in  consequence 
of  the  elastic  recoil  of  the  stretched  side. 

If  a  cell  is  beset  with  only  one  of  these  hair-like  projections,  an 
interference  with  its  motions  is  not  hkely  to  occur,  but  as  there  usu- 
all}'  are  a  number  of  cilia  situated  upon  a  single  cell,  the  question  may 
be  asked  how  they  can  avoid  beating  against  one  another.  Their 
strokes  are  of  course  very  rapid,  so  that  the  eye  is  scarcely  able  to 
follow  them.  We  thus  obtain  merely  the  impression  of  a  general 
motion  which,  however,  it  is  possible  to  render  more  conspicuous  by 
adding  some  granular  material  to  the  medium  in  which  they  are 
contained.  The  individual  granules  will  then  be  forcibly  thrown  in 
the  direction  of  the  effective  stroke  of  the  ciHa.  The  character  of 
their  beat  may  be  studied  more  advantageously  in  preparations  which 
have  been  under  observation  for  some  time,  because  the  movements 
of  dying  cilia  gradually  become  less  rapid  until  eventually  a  number  of 
them  may  be  found  which  beat  only  at  intervals.  Their  movements 
may  also  be  considerably  retarded  by  moistening  them  with  a  few  drops 
of  ice-cold  saline  solution.  Under  ordinary. conditions  the  cilia  of  the 
frog's  pharynx  beat  at  the  rate  of  12  times  in  a  second.  Their  con- 
tractions, however,  do  not  take  place  simultaneously -but  successively, 
those  in  the  front  row  of  each  field  becoming  active  first,  those  in  the 
second  next,  and  so  on,  until  the  last  one  has  been  involved.  In 
this  wa}^,  it  is  brought  about  that  the  cilia  of  each  field  present  all  the 
different  stages  of  contraction  and  relaxation  and  give  the  impression 
of  regular  waves  passing  over  them. 

The  regular  sequence  of  these  waves  of  contraction  is  not  effected 
with  the  aid  of  nervous  structures,  but  is  dependent  upon  a  proto- 
plasmic continuity  between  the  different  cells.  Naturally,  this 
action  arises  in  consequence  of  extraneous  stimuli,  but  the  impulses 
themselves  are  generated  in  the  cilium,  or  rather,  in  the  cell  to  which 
it  is  attached.  That  this  is  so,  may  be  gathered  from  the  fact  that  the 
ciUum  ceases  to  beat,  if  broken  off  at  its  base,  but  continues  to  act  if 
left  in  contact  with  at  least  a  small  fragment  of  the  cell  in  the  vicinity 
of  its  root.  The  contraction  of  the  cilia  takes  place  with  rhythmic 
regularity;  moreover,  since  it  occurs  without  the  intervention  of  the 
nervous  sj'stem,  it  may  be  said  to  be  automatic  in  its  character. 

The  function  of  the  ciha  is  entirely  mechanical,  in  that  they  impart 


42  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

motion  to  the  organism  as  a  whole  or  cause  bodies  to  move  with 
which  they  are  brought  into  contact.  Thus,  the  ciUa  hning  the  upper 
digestive  tract  of  the  frog,  beat  in  the  direction  of  the  stomach  so 
that  those  small  particles  which  are  beyond  the  reach  of  the  process 
of  deglutition,  are  nevertheless  projected  into  this  organ.  In  the 
respiratory  passage,  their  effective  stroke  is  directed  toward  the  mouth 
with  the  result  that  the  air-passages  are  constantly  cleared  of  dust 
and  mucous  globules.  In  the  female  genital  tract  they  beat  in  the 
direction  of  the  external  orifice,  and  thus  exert  a  stimulating  action 
upon  the  spermatozoa,  forcing  them  to  progress  directly  against  the 
cihary  stream.  In  those  protozoa  in  which  the  entire  external  surface, 
or  parts  thereof,  are  beset  with  cilia,  they  impart  a  motion  to  the 
entire  organism  in  a  direction  opposite  to  that  of  their  effective  stroke. 
They  act  in  this  case  in  the  manner  of  the  lateral  fins  of  the  fish.  As 
far  as  the  work  performed  by  the  cilia  is  concerned,  little  can  be  said. 
Jensen^  states  that  the  cilia  of  a  paramecium  possessing  a  length  of 
about  0.25  mm.,  are  able  to  raise  a  weight  of  0.00158  mgr.,  or  about 
nine  times  the  actual  weight  of  one  of  these  cells. 

Muscular  Movement. — In  the  higher  forms,  all  motions,  as  well  as 
the  movements  occurring  inside  the  body,  are  carried  on  with  the  help  of 
speciahzed  cells  forming  the  so-called  muscle  tissue.  These  elements 
appear  first  of  all  in  the  infusoria,  such  as  stentor  and  vorticella.  If 
one  or  the  other  of  these  organisms  is  observed  under  the  microscope, 
its  protoplasm  will  be  seen  to  be  permeated  by  a  number  of  long 
extended  fibrillse,  the  so-called  myoids.  In  stentor,  these  fibrillae 
are  arranged  singly  below  the  surface  of  the  trumpet-shaped  body, 
while  in  vorticella  they  are  cemented  together  to  form  a  thick  stalk 
upon  which  the  bell-shaped  upper  portion  of  this  organism  is  situated. 
When  in  a  condition  of  rest,  their  long  bodies  extend  far  out  into  the 
medium.  Upon  stimulation  their  head  portions  are  swiftly  retracted 
toward  the  surface  to  which  they  are  attached.  This  change  in 
their  shape  and  position  is  made  possible  by  the  contraction  of  these 
elementary  muscle  cells. 

Broadly  speaking,  these  contractile  fibrillse  reappear  in  the  higher 
animals  in  the  shape  of  the  smooth  or  non-striated  muscle  cells.  Be- 
sides, a  second  type  of  cell  is  found  here  which  possesses  a  much  greater 
complexity  of  structure  and  forms  the  chief  constituent  of  striated  mus- 
cle. The  first  enter  very  largely  into  the  formation  of  what  might  be 
termed  the  visceral  musculature  which  performs  work  in  the  interior 
of  the  body,  while  the  latter  constitute  the  skeletal  musculature  which 
is  concerned  with  the  regulation  of  the  position  of  the  animal  in  space. 
The  striated  is  under  the  direct  control  of  the  will,  while  the  non-striated 
is  not,  and  has  to  do  solely  with  the  vegetative  processes  of  hfe.  Be- 
sides these,  the  animal  body  also  contains  a  third  type  of  contractile 
tissue,  namely  the  cardiac  muscle,  but  the  function  of  this  one  is 

1  Pfluger's  Archiv,  liv,  1893,  537. 


MOTION 


43 


more  specific,  because  it  develops  the  pressure  which  is  required  to 
drive  the  blood  through  the  circulatory  channels. 

The  principle  of  action,  however,  is  the  same  in  all  three  cases, 
because  every  muscular  movement  consists  of  two  phases,  namely,  a 
period  of  contraction  and  a  period  of  relaxation.  During  the  former 
stage  the  individual  cells  or  fibers  shorten  and  thicken,  while  during 
the  latter  they  assume  their  original  long  and  thin  shape.  Obviously, 
if  each  constituent  undergoes  these  changes,  the  muscle  as  a  whole 
must  present  very  similar  alterations.  Its  contraction  is  characterized 
by  a  decrease  in  its  length  in  favor  of  its  breadth,  and  its  relaxation, 
by  a  decrease  in  its  breadth  in  favor  of  its  length.  During  the  first 
period,  therefore,  its  outline  is  more  spherical. 


Fig.  12.- 


-Stentor  Cceritleus,  Show- 
ing Myoids. 


A,  poaition  of  rest;  B,  contracted  state 
upon  stimulation. 


Fig.   13. — Vorticella. 
A,  resting  position;  B, 
upon     stimu- 


contracted 
lation. 


The  Structure  of  Muscle  Tissue.^ — The  chief  element  of  muscle 
tissue  is  the  muscle  cell  which,  in  the  case  of  the  striated  type,  is  gen- 
erally designated  as  a  fiber.  The  latter  term  seems  the  more  appro- 
priate, because  they  may  attain  a  length  of  30  to  40  mm.  or,  as  some 
authors  claim,  of  100  to  150  mm.  Their  thickness  varies  between  0.1 
to  0.01  mm.,  differing  not  only  in  different  muscles,  but  also  in  the 
same  muscle.  Their  thickness,  in  particular,  may  be  much  increased 
by  exercise  and  also  during  certain  pathological  conditions,  such  as 
hypertrophy  and  dystrophia  muscularis.  If  we  confine  ourselves  to  the 
striated  type,  constituting  the  mass  of  the  skeletal  muscu'ature,  we 
find  that  each  muscle  is  invested  by  a  connective-tissue  sheath  (peri- 
mysium) which  then  extends  into  its  interior  (epimysium)  and  forms 
small  compartments  in  which  the  individual  muscle  fibers  are  con- 

iRoUicker's  Gewebelehre,  Leipzig,  1889,  and  Schafer,  Essentials  of  Histology, 
London,  1916. 


44 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


tained.  This  connective-tissue  reticulum  serves  as  the  highway  for 
the  local  blood-vessels  and  nerves.  If  one  of  these  fibers  is  examined 
in  cross-section,  it  appears  as  a  rounded  area  possessing  a  rather  dark 
granular  center  and  a  lighter  non-differentiated  outer  zone,  or  sarco- 
plasm.  In  longitudinal  section,  these  fibers  are 
cylindrical  in  shape  and  rounded  at  their  ends, 
where  they  are  joined  with  neighboring  ones  by 
means  of  connective  tissue.  They  do  not  branch 
as  a  rule,  but  those  of  the  tongue  and  skin  divide 
^  ;     *"     into  finer  filaments  which  are  finally  inserted  in  the 

^'   mucous  membrane. 


Each  fiber  consists  of  a  thin,  hyaHne  sheath,  or  sarco- 
lemma  which  fulfills  the  purpose  of  a  cell  membrane,  and 
should  not  be  confounded  with  the  more  external  connec- 
tive-tissue envelope.  These  saccules  are  filled  with  soft 
contractile  protoplasm  arranged  in  alternate  discs  of  dark 
and  light  substance.  The  former  which  is  doubly  refracts 
ing,  or  anisotropic,  forms  the  so-called  transverse  discs,  and 
the  latter  which  is  singly  refracting,  or  isotropic,  the  so- 
called  lateral  discs.  In  the  middle  of  the  clear  band  is  seen 
a  very  delicate  dark  line  which  has  been  regarded  by  Krause 
as  a  dividing  membrane  to  mark  off  definite  segments, 
Galled  sarcomeres.  In  accordance  with  the  preceding  termi- 
nology, these  lines  may  be  referred  to  as  the  iyitermediate 
discs.  Each  fiber  is  provided  with  anumberof  nuclei  which, 
in  mammals  and  birds,  are  situated  directly  below  the  sarco- 
lemma  and  are  embedded  in  a  mass  of  sarcoplasm.  Owing 
largely  to  the  transverse  bands  which  recur  in  numbers  of 
close  to  10,000  for  each  1  cm.  of  distance,  these  muscle  fibers 
present  a  distinct  striated  appearance. ^ 

These  fibers  also  display  a  delicate  longitudinal  stria- 
tion,  for  the  reason  that  each  fiber  is  really  made  up  of  a 
number  of  extremely  fine  contractile  filaments  which  are 
arranged  parallel  to  one  another.  They  are  known  as  the. 
primitive  fihrillce  or  sarcosiyles.  These  fibrillaj  are  closely 
packed  together  in  sarcoplasm  which  unites  them  in  turn 
with  the  fibrilla;  of  neighlioring  fibers.  Hence,  each  striated 
muscle  fiber  consists  of  fibrillar,  sarcoplasm  and  sarcolemma. 
A  large  number  of  fibers  (2000)  are  bound  together  into 
muscle-bundles  which  are  separated  from  one  another  by 
the  epimysium,  and  many  bundles  into  a  muscle  which  is 
enveloped  externally  by  the  perimysium.  This  arrange- 
ment may  be  brought  out  most  clearly  in  a  muscle  which 
is  copiously  supplied  with  sarcoplasm,  by  hardening  it  in 
alcohol.  Naturally,  each  fibrilla  presents  alternate  discs  of 
dark  and  light  substance,  the  different  fibrillse  of  the  fibers 
being  arranged  in  such  a  way  that  their  cross-bands  come 
to  lie  in  practically  the  same  horizontal  plane.  In  this  con- 
nection it  should  be  remembered  that  some  of  the  higher  vertebrates  are  in 
possession  of  two  types  of  striated  muscle  tissue  which  is  either  rich  or  poor  in  sarco- 
plasm. In  fact,  certain  animals,  such  as  the  rabbit  and  different  fish,  possess  certain 
muscles  which  are  composed  of  only  one  type  of  fibers  and  thus  present  either  a  dark 
or  a  light  appearance.     The  former  are  commonly  designated  as  red  (semitendi- 

^  Gutherz,  Archiv  fur  mikr.  Anat.,  Ixxv,  1910. 


Fig.  14. — Mus- 
cular FtBEES  OF  THE 
Adductor  Magnus 
OF  A  Dog. 

M,  muscular  fiber; 
n,  nuclei;  s,  sarco- 
lemma; ee,  spaces  left 
by  the  retraction  of 
the  muscular  sub- 
stance from  the  in- 
terior of  the  sarco- 
lemma.    {Ranvier.) 


MOTION 


45 


nosus)   and  the  liitt(>r  us  i)alc  iiiusclos  (adcluftor  magiius).      It  is  readily  conceiv- 
ahle  that  this   jjcculiarity    in    tlic  tthcniical  nature  of  the  different  inuseles  must 


j!!!i;;;;;:::;a;,;;p;::;;;;!!!;;;!j 

I—"",!*?, ,.;,iw' 

fei;;;;:;::::::::::::;:;:::;:;;:;;;;;!^-, 
iffc;;.".:::::::::;::;;:;;;;..-:;;;|ji: 

^i::::;:::::::;:::;;:::;5l 


|iii|i"^:::::::::::::;t:!;";":;:^^ 

k"-;--;^::::::::::;:::::;" ■$ 

to;:;:::::::;;::;;:::;:::::";:""! 
*}''..n..,i.i..;u.i.ai":',;:;;%i 


Fig.   15.- 


-MuscLE  Fiber  of  Mammal  Highly  Magnified,  Showing  Its  Transverse 
AND  Lateral  Discs,      (a,  frovi  Schdfer;  h,  from  Sharpey.) 


lead  to  differences  in   the  strength   and'  speed   of  their  contraction.     Thus,  it  is 

found    that    the    dark    muscles    are    best 

adapted  for  the  lifting  of  heavy  loads,  while 

the     pale    muscles    excel  rather    by    their 

greater  rapidity  of  contraction.     The  latter, 

however,  are  more  easily  fatigued. 

The  more  primitive  svwoth  viuscle  tissue^ 
consists  of  spindle-shaped  cells  possessing 
either  a  cylindrical  or  a  slightly  flattened 
outline.  Their  length  varies  between  45 
and  225;u  and  their  thickness  between  4  and 
7/i.  During  pregnancy,  the  cells  of  the 
uterus  frequently  attain  a  length  of  0.5  mm. 
Inasmuch  as  these  cells  are  also  composed 
of  a  number  of  fibrillar,  they  exhibit  a  deli- 
cate longitudinal  striation.  Their  nucleus 
occupies  a  central  position  and  possesses  a 
long-oval  shape  which,  however,  becomes 
more  rounded  during  the  contracted  condi- 
tion of  the  cell.  In  its  immediate  vicinity, 
as  well  as  in  the  tapering  ends  of  the  cell,  is 
found  a  considerable  amount  of  undifferen- 
tiated protoplasm  or  sarcoplasm.  While 
the  striated  muscle  cells  are  generally  bound 
together  to  form  compact,  rounded  masses, 
the  smooth  muscle  cells  are  usuall.y  em- 
bedded in  a  heavy  substratum  of  connec- 
tive tissue,  and  the  tendency  is  to  spread  them  out  in  the  form  of  membranes 


Fig.  16. — Sensory  Nerve  Termi- 
nations IN  Arborizations  Around 
THE  Ends  of  Muscle-Fibers.  {Cec- 
cherelli.) 


1  McGill,  Am.  Jour,  of  Anatomy,  ix,  1909. 


46 


PHYSIOLOGY    OF    MUSCLE    AND    NER^T: 


Cardiac  muscle  tissue  occupies  a  special  position,  because  embryologically  as 
well  as  histologically  it  appears  in  the  form  of  modified  contractile  fibers.  This 
is  especially  evident  in  the  lower  vertebrates  in  which  these  cells  posses^  a  spindle- 
shape,  a  marked  cross-striation,  and  a  long-oval  nucleus.  In  mammals,  the  cardiac 
muscle  cell  appears  as  a  short  cylinder  which  is  usually  united  with  a  neighbor- 
ing one  by  an  obHque  process  to  form  a  muscular  plexus. ^  Functionally  it  is  of 
interest  to  remember  that  these  prolongations  bring  the  cells  of  adjoining  rows  or 


0 


B  C 

Fig.  17.  Fig.  18. 

Fig.  17. — Fibrils  of  the  Wixg  Muscles  of  a  Wasp,  Phepabed  by  Rollett's 
Method.     Highly  Magnified. 

A,  a  contracted  fibril;  B,  a  .stretched  fibril  with  its  sarcous  elements  separated  at  the 
line  of  Hensen;  C,  an  uncontracted  fibril  showing  the  porous  structure  of  the  sarcous 
elements.      (Schdfer.) 

Fig.  18. — Smooth  Muscle  Cells.  Te.\sed  Ap.a.rt  a'sd  Showixg  Long  O^'al 
Nuclei  Scrrotjnded  by  L'n'differextiated  Protoplasm. 

areas  into  closer  relation.  The  oval  nucleus  occupies  a  position  in  the  axial  portion 
of  the  cell  which  also  contains  much  undifferentiated  protoplasm,  or  sarcoplasm. 
The  other  parts  of  the  cell  e.xhibit  a  very  deUcate  cross-striation. 

The  Action  of  Striated  Muscle  in  Locomotion. — As  far  as  the 

mechanical  properties  of  the  resting  muscle  are  concerned,  we  have 
previously  seen  that  it  is  a  verj'  yielding  tissue  and  possesses  a  soft 
consistency  so  that  its  shape  may  be  varied  -^-ith  ease.  The  contracted 
muscle,  on  the  other  hand,  is  firm  to  the  touch  and  exhibits  a  more 
rounded  outline,  because  its  length  is  diminished  in  favor  of  its  breadth. 

^Zimmermann,  fber  den  Bau  der  Herzmuskulatur,  Archiv  fiir  mikr.  .\nat., 
Ixxv,  1910. 


MOTION 


47 


Thus,  as  most  striated  muscles  are  affixed  to  the  skeleton  in  such  a  way 
that  one  of  their  ends  is  stationary  and  the  other  freely  movable,  their 
contraction  invarial)ly  results  in  a  closer  approximation  of  their  points 
of  insertion  and  attachment.  In  this  way,  movements  are  produced 
which,  if  the  bones  arc  employed  as  levers,  give  rise  to  locomotion. 

A  lever  is  a  rigid  bar,  one  part  of  which  is  relatively  fixed  and  the  other  freely 
movable.  It  possesses  a  point  of  support,  or  fulcrum,  a  point  of  resistance,  or  weight, 
and  a  point  to  which  the  force,  or  power  is  applied.  In  accordance  with  the  relative 
positions  of  these  points,  we  recognize  three  different  systems  of  levers,  namely: 

(1)  The  fidcnmi  is  placed  between  the  power  and  the  weight.  When  this  lever  is 
moved,  the  weight  and  the  power  describe  arcs  the  concavities  of  which  are  turned 
toward  one  another. 


Fig.   19^.— Cardiac 
Muscle. 


Single  Cardiac 
Magn.  1000. 


(2)  The  fulcrum  is  at  one  end  and  the  weight  between  it  and  the  power.  The 
arcs  described  by  the  weight  and  the  power  are  concentric,  but  the  weight  moves 
less. 

(3)  The  fulcrum  is  at  one  end  and  the  power  between  it  and  the  weight.  The 
arcs  are  concentric,  but  the  weight  moves  a  greater  distance  than  the  power. 

As  an  example  of  a  lever  of  the  first  order  might  be  mentioned  the  movement  of 
the  skull  upon  the  spinal  column.  The  articulation  between  the  axis  and  occipital 
bone  serves  in  this  case  as  the  fulcrum,  the  face  as  the  weight  and  the  posterior 
muscles  as  the  power.  As  an  example  of  a  lever  of  the  second  order  may  serve  the 
foot  when  employed  to  raise  the  body  upon  the  toes.  The  fulcrum  is  formed  in 
this  case  bj-  the  toes  resting  upon  the  ground,  the  weight  by  the  body  resting  upon 
the  ankle-joint  and  the  power  by  the  gastrocnemius  and  soleus  muscles.  As  an 
example  of  a  lever  of  the  third  order  might  be  mentioned  the  arm  when  it  executes 
the  movement  of  flexion.  In  this  case,  the  fulcnmi  is  formed  by  the  elbow-joint, 
the  weight  by  the  hand  and  the  power  by  the  biceps  muscle,  the  tendon  of  which 
is  inserted  in  front  of  the  elbow-joint.  These  three  systems  may  also  be  illustrated 
by  giving  to  the  foot  the  three  different  positions  indicated  in  Fig.  21. 


48 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


Theories  of  Muscular  Contraction. — The  contracting  striated 
muscle  also  presents  certain  microscopic  changes  which  have  been  em- 
ployed in  the  formulation  of  several  theories  regarding  the  manner 
in  which  the  contraction  is  brought  about.     To  begin  with,  it  should 


r 


w 


I   ^ 


F 


W 


Fig.  20. — Different  Systems  of  Levers. 
F,  fulcrum;  P,  power;  W,  weight. 

be  remembered  that  the  different  elements  composing  a  muscle,  do  not 
contract  simultaneously,  but  successively,  those  nearest  the  seat  of  the 
stimulation  being  activated  first.  Consequently,  the  contraction 
progresses  over  the  muscle  in  the  form  of  a  wave  which  is  directed 
toward  the  part  farthest  removed  from  the  point  stimulated.     The 


Fig.   21. — Different  Positions  Given  to  the  Foot  in  Illustr.\tion  of  the  Three 

Systems  of  Levers. 

details  of  this  wave  of  contraction  may  be  studied  under  the  micro- 
scope in  fresh  preparations  of  muscle  from  the  legs  or  wings  of  insects. 
Moreover,  if  a  muscle  is  dropped  into  alcohol  or  osmic  acid,  a  series 
of  waves  are  evoked  in  its  component  fibers  which  are  then  fixed  as 
nodular  or  fusiform  swellings. 


MOTION 


49 


It  is  commonly  beliovod  that  the  primary  source  of  the  energy  of 
muscle  is  to  be  found  in  the  interaction  of  several  of  its  chemical  con- 
stituents. The  potential  energ}'  here  stored  is  transformed  into  kinetic 
energy  of  the  mechanical  variety  in  accordance  with  the  law  of  the 
conservation  of  energ^y.  Thus,  the  resting  muscle  represents  an  un- 
stable system  which  may  readily  l)e  transformed  l)y  the  mere  appli- 
cation of  a  stimulus.  The  question  now  arises,  how  is  it  possible  that 
this  explosive  process  leads  to  a  shortening  of  the  individual  muscle 
fibers  as  well  as  of  the  muscle  as  a 
whole?  Several  explanations  are 
at  hand,  although  the  best  of  them 
cannot  be  said  to  be  absolutely 
satisfactory. 

Weber^  has  claimed  that  the 
contraction  of  muscle  results  in  con- 
sequence of  the  sudden  alteration  of 
its  elastic  power,  this  change  being 
brought  about  by  a  chemical  trans- 
formation following  in  the  wake  of 
the  stimulus.  These  internal 
chemical  forces  tend  to  cause  varia- 
tions in  the  elastic  equilibrium  of 
the  muscle,  leading  to  a  change  in 
its  form.  In  accordance  with  the 
view  of  Mayer  (1845),  muscle  tissue 
may  be  compared  to  a  steam  engine 
which  transforms  the  heat  generated 
by  it  into  mechanical  energy.  En- 
gelmann-  assumed  later  on  that  the 
heat  evolved  results  in  a  transfer  of 
molecules  of  water  and  a  change  in 
the  form  of  the  muscle  as  a  whole. 


Fig.  22. — Artificial  Muscle. 
The  artificial  muscle  is  represented 
by  the  catgut  string,  m.  This  is  sur- 
rounded by  a  coil  of  platinum  wire,  u\ 
through  which  an  electrical  current  may 
be  sent.  The  catgut^  is  attached  to  a 
lever,  h,  its  fulcrum  is  at  c.  The  cat- 
gut is  immersed  in  a  beaker  of  water 
at  50°  to  55°  C,  and  "stimulated"  by 
the  sudden  increase  in  temperature 
caused  by  the  passage  of  a  current 
through  the  coil.  (Howell,  after  Engel- 
mann.) 


This  assumption  has  given  rise  to  the 
so-called  thermodynamic  theor\^  of  mus- 
cular contraction  which  is  based  upon 
the  observation  that  the  contracting 
fiber  suffers  an  inversion  of  its  elements, 
i.e.,  the  dark  discs  become  more  fluid  and 

lighter  in  color,  while  the  light  discs  become  more  compact  and  darker.  But  as 
the  width  of  the  contracting  portion  of  the  fiber  becomes  greater,  both  bands  must 
be  pushed  out  laterally  and  must  therefore  decrease  in  height.  Engelmann  then 
assumed  that  the  contraction  of  the  fiber  is  caused  by  a  rapid  transfer  of  water 
from  the  isotropic  into  the  anisotropic  substance  under  the  influence  of  the  chemical 
energy  set  free  in  the  form  of  heat.  This  imbibition  with  molecides  of  water  tends 
to  impart  a  more  oval  or  spherical  shape  to  the  individual  contractile  elements. 
Later  on,  as  the  heat  is  di.ssipated,  the  water  again  returns  into  the  light  substance 
and  causes  the  fiber  to  relax.     Engelmann  has  imitated  this  process  of  swelling 

1  Muskelphysik.,  1846. 

2  Pfliiger's  Archiv,  .xi,  1875,  432  and  x.xv,  1881,  538. 


50  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

and  shortening  with  the  help  of  a  vioHn  string  which  he  first  pjissed  through  a  coil 
of  platinum  wire  and  then  attached  under  some  tension  to  a  writing  lever.  If  this 
string  was  immersed  in  water  and  then  subjected  to  heat  by  passing  an  electrical 
current  through  the  wire,  it  shortened  very  considerably.  The  subsequent  dis- 
continuance of  the  current  permitted  the  string  to  regain  its  original  length.  The 
curves  recorded  in  this  manner  are  very  similar  to  those  obtained  with  muscle 
preparations  under  ordinary  conditions  of  experimentation. 

Ranvieri  agrees  with  Engelmann  in  so  far  as  he  believes  that  the  anisotropic 
substance  is  the  only  contractile  part  of  the  fiber.  He  holds,  however,  that  the 
anisotropic  discs  lose  water  on  contraction  which  is  transferred  to  the  interfibrillar 
substance.  Schafer^  adheres  to  Engelmann's  hypothesis  and  states  further  that 
the  anisotropic  substance  is  permeated  by  minute  channels  which  run  parallel  to 
the  axis  of  the  fiber  and  serve  to  accommodate  isotropic  material.  In  consequence 
of  the  filling  of  these  canaliculi  the  individual  segments  or  prisms  of  the  anisotropic 
substance  are  forced  farther  apart,  causing  a  widening  of  the  fiber  on  contraction. 

Absorption  is  also  the  principle  of  the  hypothesis  of  McDougall.^  It  is  be- 
lieved that  the  sarcostyles  or  fibrillse  of  striated  muscle  are  constructed  in  such  a 
way  that  their  distention  immediately  produces  a  reduction  in  their  length.  This 
distention  is  assumed  to  take  place  as  a  result  of  an  influx  of  the  sarcoplasmic  fluid 
which  surrounds  them.  Meigg''  has  applied  this  conception  to  smooth  muscle  and 
claims  that  its  contraction  is  dependent  upon  the  passage  of  fluid  from  the  cell 
into  the  interstitial  spaces. 

A  hypothesis  has  also  been  formed  by  Miiller^  which  attributes  muscular 
contraction  to  an  electrical  attraction  and  repulsion  of  doubly  refracting  crystal- 
loids. In  consequence  of  a  production  of  heat,  these  bodies  change  their  poten- 
tial, relaxation  resulting  when  the  polarity  subsides  owing  to  the  equalization  of 
the  temperature.  It  is  a  well-known  fact  that  muscular  contraction,  as  well  as 
any  other  activity  of  protoplasm,  is  associated  with  electrical  variations,  but  these 
changes  have  been  proved  to  be  quite  independent  of  contractility."^  All  these 
hypotheses  are  very  indefinite.  Based  upon  the  work  of  Berthold^  a  hypothesis 
has  been  formulated  by  Verworn^  which  holds  that  the  chemical  changes  in  muscle 
result  in  alterations  in  the  surface  tension  of  the  isotropic  and  anisotropic  discs. 
In  consequence  of  these  variations,  the  histological  constituents  of  muscle  change 
their  power  of  cohesion  and  adhesion  and  hence,  their  shape  and  position.  Jenson' 
has  put  forward  the  so-called  coagulation-hypothesis  which  bases  the  contraction  of 
muscle  upon  changes  in  the  aggregate  condition  of  the  sarcoplasm.  In  accordance 
with  this  view,  its  relaxation  is  not  regarded  as  a  passive  phenomenon,  but  is  said 
to  occur  in  consequence  of  processes  the  reverse  of  the  former. 

It  is  to  be  noted  especially  that  the  contraction  of  muscle  re- 
quires merely  an  internal  readjustment  of  its  constituents  and  does 
not  involve  changes  m  its  volume  which  could  only  be  had  by  a 
transfer  of  material  from  and  to  other  tissues.  This  fact  may  be 
proved  by  placing  a  muscle  in  a  glass  receptacle  filled  with  boiled 
saline  solution,  and  equipped  with  a  capillary  tube  in  which  the  water 

^  Legons  d'anat.  gen.  sur  le  syst.  muse,  Paris,  1880. 

2  Proc.  Royal  Society,  xUx,  1891. 

3  Journ.  of  Anat.  and  Physiol.,  xxi,  1897,  410;  and  xxii,  1898,  187. 

*  Am.  Journ.  of  Physiol.,  xxii,  1908,  476;  also  Hurthle,  Pfluger's  Archiv,  cxxvi, 
1909,  1. 

^  Theorie  der  Muskelkontraktion,  Leipzig,  1891. 

«  Helmholtz  (1855)  and  Biedermann,  ElektrophysioL,  Jena,  1895. 

^  Studien  iiber  die  Protoplasma  Mechanik,  Leipzig,  1886. 

8  Allg.  Physiologic,  Jena,  1910;  and  Saleotti,  Zeitschr.  fiir  Allg.  Physiol., 
vi,  1906. 

^  Pfluger's  Archiv,  c.xx.xvii,  1901,  367. 


MOTION 


51 


forms  a  meniscus.     If  tlie  muscle  is  now  made  to  contract,  it  will  be 
seen  that  the  meniscus  docs  not  move. 

The  Excitation  of  Muscle. — We  have  seen  that  all  movements 
which  are  to  be  carricul  out  witli  precision,  are  cflfectcd  by  means  of 
striated  nuiscle.  In  nearly  all  cases  this  tissue  is  under  the  control 
of  the  central  nervous  system  and  especially  of  the  cerebrum  which 
gives  rise  to  volition.  Non-striated  muscle,  on  the  other  hand,  is  not 
absolutel}^  dependent  upon  central  nervous  structures,  but  is  regulated 
by  peripheral  or  local  centers.  For  this  reason,  it  is  able  to  show  a 
marked  degree  of  spontaneity  and  is,  therefore,  not  wholly  under  the 
guidance  of  the  will.  It  is  true,  however,  that  its  independency  is 
not  absolute,  because  its  connection  with  the 
cerebrospinal  system  is  necessary  to  bring  it  into 
functional  relation  with  other  parts  of  the  body. 

The  different  muscles  are  connected  with  the 
central  nervous  system  by  means  of  nerves  which 
conduct  impulses  either  toward  them  or  away 
from  them.  Hence,  muscle  tissue  must  be  in 
possession  of  two  types  of  end-organs,  namely 
one  for  the  reception  of  the  stimuli  and  one  for 
the  production  of  the  motor  reaction.  The  sen- 
sory end-organ  or  muscle-spindle,  is  composed  of 
a  group  of  delicate  fibers  which  are  invested  by 
a  thick  covering  of  perimysium.  Around  these 
the  nerve  terminals  are  arranged  in  the  form  of 
spirals  or  rings.  The  motor  end-organ,  or  motor 
plate,  consists  of  a  bulbular  enlargement  of  the 
axis    cylinder    which    is    pressed  flat  against  the  Show  That  Contra cr- 

,  -     ,  1        ,-1  T,  iNG  Muscle  Does  Not 

sarcolemma  or  the  muscle    fiber.     It 


\ 

^y 

iTn 

iJ:i||iii(/i 

iiiiiiiiiiii 

^yJn" 

-  - 1  ■    ',,/i  -^- 

-f-f'  \l 

V\ii 

-  !__    - 

Fig.  23.— Schema  to 


appears    as   change  Its  Volume. 


a  rounded  granular  mass,  the  substance  of  which 
contains  numerous  nuclei. 


M,  meniscus  of  sa- 


lt is   invested   solely   line    solution;    S,    elec- 
T_  ,  1  •   ]     •      !•        J.1  J.'  -J.!     trodes    through    which 

by  neurolemma  which  is  directly  continuous  with  muscle  in  receptacle  is 
the  sarcolemma.  The  medullary  sheath  dis-  stimulated. 
appears  at  some  distance  from  the  motor  plate, 
namely,  at  the  point  where  the  nerve  fiber  begins  to  divide  to  form  this 
ramification  of  axis  cylinders.  Most  generally,  a  single  muscle  fiber 
contains  only  one  of  these  motor  plates,  but  if  it  is  very  long,  it  usually 
embraces  two  or  several  of  these  endings.  The  different  nerve  fibrils 
arising  from  these  plates,  unite  into  larger  ones  so  that  their  number 
is  much  reduced  when  leaving  the  muscle.  That  this  is  a  very  econom- 
ical arrangement  may  be  gathered  from  the  fact  that  inasmuch  as  a 
muscle,  such  as  the  oculomotorius,  contains  about  15,000  muscle  fibers, 
about  180  million  nerve  fibers  would  be  required  for  30,000  grams  of 
muscle  substance.  Stilling,  however,  has  found  only  about  30,000 
fibers  in  the  anterior  roots  of  the  spinal  cord.  In  smooth  muscle,  the 
individual  nerve  fibers  terminate  in  complicated  networks  which  are 


52 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


beset  with  ganglion  cells.     From  these  plexuses  delicate  fibrils  then 
pass  to  the  different  muscle  cells. 

Under  ordinary  conditions,  a  muscle  contracts  only  in  response 

to  impulses  generated  in  the  central  nervous  system  and  conveyed 

to  it  through  its  nerve.     Under  experimental  conditions,  however, 

these  impulses  may  be  generated  anywhere  along  the  course  of  the 

nerve,  and  most  easilj^  by  electrical  or  mechanical 

stimuli.     The  natural  excitatory  agents  are  usually 

designated  as  adequate  stimuli  and  the  uncommon 

ones,  as  inadequate  stimuli.     It  is  also  possible  to 

produce  a  contraction  of  a  muscle  by  stimulating 

it  directly.     In  the  latter   case  the  stimulation  is 

said  to  be  direct,  while  the  activation  of  the  muscle 

through  its  nerve  constitutes  the  method  of  indirect 

stimulation. 

Independent  Irritability  of  Muscle. — If  a  muscle 
is  stimulated  directl}',  it  may  be  contended  that  it 
reacts  in  consequence  of  the  excitation  of  its  ner- 
vous constituents  and  not  on  account  of  the  exci- 
tation of  its  myoplasmic  elements.  Obviously,  it 
is  quite  impossible  under  ordinary  conditions  to 
differentiate  between  these  two  factors,  unless  one 
of  them  can  be  rendered  temporarily  useless.  An 
experiment^  enabling  us  to  exclude  the  nervous 
elements  may  be  performed  as  follows:  Having 
isolated  the  sciatic  nerve  of  a  frog  in  the  region 
of  the  thigh,  a  ligature  is  tightly  drawn  around 
all  the  other  tissues  of  this  part.  The  blood 
supply  having  thus  been  cut  off  from  this  extremity, 
a  few  drops  of  curare-  are  injected  into  the  dorsal 
lymph-sac.  About  20  to  30  minutes  later,  the  op- 
posite sciatic  nerve  is  isolated,  and  a  small  opening 
made  in  the  skin  over  each  gastrocnemius  muscle. 
As  soon  as  the  curare  has  taken  effect,  the 
stimulation  of  the  sciatic  nerve  fails  to  evoke  a 
contraction  of  the  gastrocnemius  on  the  side  which 
has  not  been  hgated  (at  2),  but  produces  a  reaction 
on  the  side  of  the  Ugature  (at  1).  If  the  gastroc- 
nemii  muscles  are  now  stimulated  directly  (at  3 
and  4),  it  will  be  found  that  both  are  responsive.  By  applying  a 
galvanometer  to  the  sciatic  nerve  of  the  leg  which  has  not  been 
ligated,  it  may  readily  be  proved  that  this  nerve  has  retained  its 
functional  power,  because  every  stimulus  gives  rise  to  a  deflection  of 

1  Archiv  fur  path.  Anat.,  1856,  or  Claude  Bernard,  Comp.  rend.,  1856,  825. 

2  Curare,  wurare  or  urare  is  a  poison  used  by  South  American  Indians  upon 
arrows  and  other  weapons.  It  is  prepared  from  the  roots  of  the  wurare  plant, 
a  concoction  being  formed  with  other  ingredients  to  hide  the  real  active  principle. 


Fig.  24. — Inde- 
pendent Irritabil- 
ity OF  Muscle. 

A,  dorsal  lymph 
sac  into  which  curare 
is  injected;  L,  liga- 
ture upon  left  thigh. 
The  stimulation  of 
the  sciatic  nerve  at  1 
is  then  effective  but 
ineffective  at  2. 
Both  gastrocnemius 
muscles,  when  stimu- 
lated directly  at  3 
and  4,  give  a  contrac- 
tion. 


GRAPHIC   REGISTRATION    OF   MUSCULAR    CONTRACTION         53 

the  needle  of  this  instrument.  The  above  results  clearly  show  that 
the  curare  has  destroyed  the  connection  between  the  nerve  and  the 
muscle  substance.  In  other  words,  this  agent  has  paralyzed  the 
motor  plate,  so  that  the  centrifugal  impulses  can  no  longer  reach 
their  destination.  On  the  side  on  which  the  curare  has  been  prevented 
from  producing  its  characteristic  effect  by  the  hgature,  the  impulses 
pursue  as  before  a  perfectly  straight  course  into  the  muscle.  The  latter 
fact  may  also  be  demonstrated  by  stimulating  the  central  end  of  the 
sciatic  nerve  on  the  curarized  side.  The  impulses  here  generated  now 
travel  in  a  centripetal  direction  into  the  cord,  whence  they  attain  the 
opposite  gastrocnemius  muscle  by  the  sciatic  nerve  of  the  non-cura- 
rized  side.  Clearly,  therefore,  the  normal  muscle  may  also  be  stimu- 
lated reflexly. 

The  chief  conclusion  to  be  derived  from  this  experiment,  is  this: 
Inasmuch  as  the  nervous  elements  in  the  muscle  have  been  rendered 
functionally  useless  by  the  curare  without  destroying  the  susceptibility 
of  the  muscle  substance  to  direct  stimulation,  it  must  necessarily 
follow  that  the  myoplasm  is  independently  irritable.  In  other  words, 
normal  myoplasm  is  capable  of  receiving  stimuli  and  of  reacting  even 
without  the  aid  of  nervous  tissue.  This  conclusion  may  be  substan- 
tiated by  other  facts.  Thus  it  has  been  observed  that  the  hearts  of 
embryos  possess  rhythmical  activity  long  before  any  nerve  tissue  can 
be  recognized  within  them.  Moreover,  if  the  motor  nerve  of  a 
muscle  is  cut,  it  undergoes  degenerative  changes  and  finally  becomes 
functionally  useless.  At  this  time,  however,  it  is  still  receptive  to  direct 
stimulation.  Kiihne,  moreover,  has  observed  that  the  sartorius 
muscle  of  the  frog  reacts  even  if  stimulated  at  its  very  end,  in  spite 
of  the  fact  that  its  ends  are  devoid  of  nerve  fibers.  In  addition,  Schiff 
has  shown  that  dying  muscle  reacts  toward  mechanical  impacts  by 
a  local  contraction,  i.e.,  the  fibers  near  the  seat  of  the  irritation  are 
drawn  together  into  a  nodular  swelling. 


CHAPTER  IV 


THE  GRAPHIC  REGISTRATION  OF  MUSCULAR  CONTRACTION 
METHODS  OF  STIMULATION  OF  MUSCLE  AND  NERVE 

A.  Muscle -nerve  Preparation. — While  no  serious  objection  can 
be  raised  against  the  use  of  almost  any  muscle,  our  knowledge  regard- 
ing the  behavior  of  this  tissue  has  been  gathered  chiefly  from  prepara- 
tions of  the  gastrocnemius  and  sartorius  muscles  of  the  frog,  owing  to 
the  relative  ease  with  which  they  may  be  isolated  and  rendered  ac- 
cessible to  the  recording  apparatus.  It  is  also  true  that  the  muscles 
of  cold-blooded  animals  retain  their  irritability  after  their  removal  from 


64  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

the  body  for  a  much  longer  time  than  those  of  warm-blooded  animals. 
It  is  a  simple  matter  to  reflect  the  skin  from  the  leg  of  a  pithed  frog 
and  to  isolate  the  gastrocnemius  muscle  by  cutting  through  the  tendo 
Achillis  and  the  fascia  uniting  it  with  the  neighboring  tibia.  This  bone 
is  then  cut  through  directly  below  the  knee-joint.  Above  the  latter 
is  found  the  sciatic  nerve  which  may  be  traced  along  the  posterior 
aspect  of  the  thigh  into  the  pelvis  where  its  three  roots  are  seen  to  arise 
from  the  posterior  end  of  the  spinal  cord.  It  should  be  divided  at  this 
point  and  carefully  separated  all  the  way  down  to  the  muscle  with 


Tib.  ant.  long, 


Tendo  Achillis 


Fig.  25. — Muscles  of  Hind  Leg  of  Frog.      (Ecker.) 

which  it  must  of  course  be  left  in  contact.  The  fibers  of  the  gastroc- 
nemius muscle  are  short  and  are  arranged  obliquelj^  into  a  compact 
mass  of  tissue.  For  this  reason,  the  actual  shortening  of  this  muscle  is 
really  quite  inconsiderable  in  comparison  with  its  power  of  contraction. 
In  the  sartorius  muscle,  on  the  other  hand,  the  fibers  are  long  and  are 
placed  more  parallel  to  one  another.  This  is  also  true  of  the  gracihs 
and  semimembranosus  muscles.  Preparations  of  the  latter  give  high 
contractions,  but  the  weight  which  they  are  able  to  lift  is  relatively 
small. 

Methods   of  Registration.     Myography. — Soon   after  the  experi- 
ments of  E.   Weber   (1846),  pertaining  to  the  elasticity  of    muscle, 


GRAPHIC    REGISTRATION    OF    MUSCULAR    CONTRACTION 


55 


Helmholtz  (1850-1852),  devised  a  recording  apparatus  which  he  desig- 
nated as  a  myograpii.  This  instruinont  has  subsequently  been  modi- 
fied by  Pfliiger,  Fick  and  Du  Bois-Reyniond.  It  would  lead  us 
altogether  too  far  to  give  even  a  tolerably  accurate  description  of  these 
and  other  graphic  appliances,  and  hence,  it  may  suffice  to  say  that  the 
registration  of  the  contraction  of  muscle  necessitates  first  of  all  a 
means  of  holding  the  muscle,  secondly,  an  outfit  for  recording  its 
movements,  and  thirdly,  a  surface  upon  which  this  record  may  be 
made.  One  end  of  the  freshly  excised  muscle  is  fastened  in  a  station- 
ary clamp,  while  the  other  is  connected  by  means  of  a  string  with  a 
writing  lever  placed  horizontally  underneath  it.     This  lever  should  be 


i'l 

V'li' 

ll 

; 

K 

'  1 

^  1 

1 
,1 

r^. 

— 

1 

F     1 
1 

1 

-  o 

•1 

Fig.  26. — A  Method  Used  to  Register  Muscular  Contraction. 
St,  stand  for  holding  of  clamp  C  and  writing  lever.      WL,  the  muscle  M  is  attached  to 
the  lever  by  means  of  a  small  hook  and  string.     The  lever  is  counterpoised  by  weight  W . 
The  stimulation  is  effected  through  the  electrodes,  .S.    The  speed  of  the  kymograph  K 
may  be  varied  by  fan  F. 

properly  counterpoised  by  weights  or  tension  springs  so  as  not  to 
extend  while  it  rests.  Moreover,  the  muscle  should  be  surrounded  by 
a  small  bell  jar  so  as  to  be  able  to  keep  it  under  proper  conditions  of 
moisture  and  temperature.  The  recording  surface  generally  employed 
to-day,  consists  of  a  sheet  of  glazed  paper  which  is  attached  to  the 
cylindrical  drum  of  a  kymograph  and  is  then  evenly  covered  with  soot 
by  rotating  it  in  a  broad  gas  flame.  The  drum  carrying  the  blackened 
paper,  is  moved  by  clockwork  at  different  speeds,  the  velocity  of  its 
movement  being  indicated  in  seconds  by  a  chronograph  which  is  ad- 
justed underneath  the  muscle  lever.  If  the  rotation  is  rapid,  an  ordi- 
nary tuning  fork  may  be  permitted  to  register  its  vibrations  below  the 
myogram. 


56 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


Isotonic  and  Isometric  Myograms. — If  a  muscle  is  made  to  contract 
after  it  has  been  attached  to  the  writing  lever,  it  must  suffer  an  initial 
stretching  and  this  stretching  must  be  the  greater,  the  heavier  the 
load  against  which  it  acts.  A  certain  part  of  its  energy,  therefore,  must 
be  lost  without  being  able  to  produce  a  visible  effect.  To  counteract 
this  distention,  it  is  customary  to  after-load  the  muscle  with  a  slight 
weight  which  is  neither  increased  nor  diminished  during  the  contrac- 
tion, or  to  hold  the  writing  lever  in  a  horizontal  position  by  means  of 
a  support  or  a  tension  spring.  While  thus  subjected  to  the  least  pos- 
sible tension,  it  is  not  hindered  in  changing  its  length  and  in  generating 


^ 


[ia      B 


Fig.  27. — Different  Ways  of  Counterpoising  the  Writing  Lever. 
A,  B  and  C,  isotonic  arrangements;  D,  isometric  arrangement;  S,  spring. 

visible  mechanical  energy.  A  myogram  obtained  under  this  condition 
is  characterized  as  isotonic.  As  far  as  the  adjustment  of  the  muscle 
and  weight  is  concerned,  the  latter  may  be  affixed  (a)  directly 
beneath  the  point  of  attachment  of  the  muscle  (method  of  loading), 
(b)  precisely  in  the  same  place  with  this  modification,  however,  that 
the  lever  is  held  in  a  horizontal  position  by  a  counterpoising  load 
or  other  appliance  (method  of  after-loading),  and  (c)  to  the  axis  of 
the  lever  by  means  of  a  pulley.  The  latter  arrangement  gives  the 
most  perfect  isotonicity. 

If  the  muscle  is  attached  near  the  fulcrum  of  the  writing  lever, 


GRAPHIC    REGISTRATION    OF    MUSCULAH    CONTRACTION         57 


while  at  the  same  time  the  long  arm  of  the  latter  is  prevented  from 
moving  upwards  by  a  counter  force,  such  as  a  spring  (Fig.  27D), 
the  shortening  of  the  muscle  will  be  insignificant  in  comparison  with 
the  tension  to  which  it  is  subjected.  A  curve  of  this  kind,  displaying 
almost  no  change^  in  the  length  of  the  muscle  and  practically  no  me- 
chanical energy,  is  characterized  as  isometric.  In  this  way,  a  relatively 
much  larger  proportion  of  the  total  energy  liberated  is  transferred  into 
heat.  While  the  muscles  ordinarily  used  by  us  in  the  production 
of  work,  are  not  arianged  in  a  strictly  isometric  manner,  our  con- 
tractions most  generally  possess  an  isometric 
character  for  the  reason  that  they  are  ex- 
ecuted against  resistances. 

Electrical  Stimulation.  Battery.  Poten- 
tial. Strength  of  Current.  Resistance. — A 
muscle-nerve  preparation  may  of  course  be 
subjected  to  the  different  kinds  of  stimuli 
mentioned  previously,  namely,  mechanical, 
such  as  may  be  produced  by  pricking  or 
pinching;  chemical,  such  as  result  from  con- 
tact with  sodium  chlorid  and  other  agents; 
thermal,  such  as  may  be  caused  by  a  heated 
wire,  and  electrical.  Any  one  of  these  influ- 
ences may  be  brought  to  bear  upon  the 
muscle  directly  or  through  the  intervention 
of  its  nerve.  Under  ordinary  conditions  of 
experimentation  preference  is  given  to  the 
electrical  method  of  stimulation,  because  it 
is  by  far  the  most  convenient,  and  although 
the  electricity  may  be  produced  by  a  mag- 
net or  by  friction,  the  common  practice  is 
to  derive  it  from  a  Voltaic  cell. 


Cu 


Fig.  28. — Diagram  of 
Daniell  Cell. 

Cu,  copper  plate  (+);  Z, 
zinc  plate  (— ).  The  direc- 
tion of  the  current  is  indicated 
by  the  arrows. 


The  place  of  the  generator  may  be  taken  by  a 
Daniell,  Grove  or  Leclanche  cell.  The  first  consists 
of  a  glass  jar  filled  .with  a  concentrated  solution  of 

sulphate  of  copper  in  which  is  immersed  a  round  sheet  of  copper.  Inside  the  latter 
is  a  porous  earthen  cup  filled  with  dilute  sulphuric  acid  in  which  is  contained  a  rod  of 
zinc.  If  the  outside  poles  of  this  cell  are  now  connected  by  wires,  the  current  leaves 
at  the  copper  and  enters  at  the  zinc.  The  former  pole,  therefore,  is  the  positive 
pole  or  anode,  and  the  latter,  the  negative  pole  or  cathode.  Inside  the  cell,  of 
course,  conditions  are  reversed,  because  in  order  to  complete  the  circuit  the  current 
must  flow  from  the  zinc  to  the  copper.  The  former,  therefore,  must  be  positive 
and  the  latter  negative.  A  cell  of  this  kind  generates  a  constant  electromotive 
force  of  about  1.07  volts,  but  possesses  the  disadvantage  of  giving  off  fumes  and 
acids  and  requires  to  be  renewed  from  time  to  time.  These  difficulties  are  not 
present  in  the  so-called  drj^  cell  which  is  usually  a  modified  type  of  the  Leclanche 
cell.  The  latter  consists  of  a  glass  jar  filled  with  a  saturated  solution  of  ammonium 
chlorid  and  containing  a  plate  of  amalgamated  zinc.  The  inner  area  of  this  cell 
is  occupied  by  a  porous  cup,  containing  pieces  of  carbon  and  dioxid  of  manganese. 
The  plate  of  carbon  projecting  from  this  mixture  forms  the  positive  pole,  while  the 
negative  pole  is  represented  by  the  zinc.     The  electromotive  power  of  this  cell 


58  PHYSIOLOGY  OF  MUSCLE  AND  NEEVE 

is  1.5  volts.  The  ordinary  type  of  dry  cell  consists  of  a  zinc  jacket  lined  with 
plaster  of  Paris  and  saturated  with  ammonium  chlorid.  Its  inner  space  is  taken 
up  by  a  carbon  plate  surrounded  by  black  oxid  of  manganese. 

While  the  nature  of  electricity  has  not  been  recognized  as  yet,  we  know  that  an 
electrical  current  passes  over  a  system  of  wires  in  the  same  manner  as  water  flows  from 
a  high  to  a  low  level.  It  leaves  the  generator  at  its  place  of  high  electrical  potential 
and  reenters  it  at  its  place  of  low  potential.  The  point  of  e.xit  forms  the  positive 
pole  or  anode  (ana  =  up)  and  the  point  of  entrance,  the  negative  pole,  or  cathode 
(cata  =  down).  The  difference  in  the  potential  between  these  two  points  is 
designated  as  the  electromotive  force.  It  is  easy  to  understand  that  this  difference 
can  only  be  kept  up  if  there  is  a  constant  supply  of  current.  As  the  zinc  is  being 
dissolved,  the  chemical  energy  liberated  thereby  tends  to  maintain  a  constant 
electrical  pressure  at  the  two  poles.  The  cell,  therefore,  represents  a  reservoir  of 
electricity  which  remains  filled  as  long  as  there  is  sufficient  material  present  to 
generate  chemical  energy.  If,  however,  the  material  is  used  up,  the  difference  in 
potential  can  no  longer  be  maintained  and  an  equalization  must  finally  result 
which  causes  the  current  to  cease.  In  this  regard  electricity  beliaves  like  water, 
because  the  flow  of  the  latter  from  a  reservoir  continues  only  as  long  as  the  outgo 
is  balanced  by  an  adequate  ingo. 

While  traversing  a  system  of  wires  the  electrical  current  loses  a  certain  amount 
of  its  initial  energy,  owing  to  the  resistance  which  it  must  overcome.  Hence,  the 
strength  of  the  current  or  the  rate  of  flow  of  electricity  between  two  different  points 
of  a  conductor  is  dependent  not  only  upon  the  electromotive  force  but  also  upon 
the  resistance  resident  in  the  conducting  path.  Obviously,  if  the  poles  of  a  cell  are 
connected  by  means  of  a  short  and  thick  wire,  the  resistance  to  be  overcome  will  be 
less  than  if  joined  by  a  long  and  thin  wire.  In  the  former  case,  therefore,  the  flow 
of  electricity  will  be  greater  than  in  the  latter,  provided,  of  course,  that  the  electro- 
motive force  remains  imaltered.  It  must  also  be  evident  that  the  strength  of  a 
current  through  a  certain  length  and  thickness  of  wire  must  be  directly  proportional 
to  the  electromotive  force.  In  addition  to  this  external  resistance  which  the  elec- 
trical current  encounters  in  its  passage  through  a  conductor  from  copper  to  zinc, 
it  must  also  overcome  the  internal  resistance,  resident  in  the  constituents  of  the  cell 
between  the  zinc  and  copper.  Provided  that  the  conducting  power  of  the  liquid 
remains  the  same,  the  resistance  must  decrease  with  the  size  of  the  plates  and 
increase  with  the  distance  between  them. 

Measurement  of  Electrical  Quantities. — In  accordance  with  the 
metric  system,  a  unit  of  current  is  designated  as  an  ampere,  a  unit 
of  electromotive  force  as  a  volt,  and  a  unit  of  resistance  as  an  ohm. 
An  ohm  equals  the  resistance  of  a  column  of  mercury  1  mm.  in  cross- 
section  and  1063  mm.  in  length  at  0°  G.  The  electromotive  force  or  the 
electrical  pressure,  so  to  speak,  of  a  Daniell  cell  is  about  one  volt. 
If  this  power  is  permitted  to  act  through  a  resistance  of  one  ohm, 
a  current  of  approximately  one  ampere  is  obtained.  In  the  case  of  the 
Daniell  cell,  however,  the  amperage  is  really  somewhat  smaller,  because 
even  if  the  outside  wire  possesses  a  resistance  of  only  one  ohm,  the  total 
resistance  to  be  overcome  by  the  current  is  actually  greater,  owing  to 
the  fact  that  it  is  also  opposed  by  the  internal  resistance  of  the  cell. 
The  relationship  existing  between  these  different  factors  has  been 
determined  experimentally  by  G.  S.  Ohm  (1827),  in  accordance  with 
the  following  formula : 

^  ,    ,         ,,  electrom.  force  volts      c,. 

Current  strength  =  ^p— ,   -r,  ^ -or  amperes  =  -r — '     bmce 

*         Int.  res.  +  Ext.  res.  ohms 

these  factors  are  very  closely  related,  it  is  possible  to  determine  any 


GRAPHIC    REGISTRATION    OF   MUSCULAR   CONTRACTION         59 


one  of  them,  provided  the  values  of  the  other  two  are  known.     Thus: 

volts  =  amperes  X  ohms 
amperes  =  volts  -r-  ohms 
ohms       =  volts       -^  amperes 

Polarization. — The  two  metals  of  a  battery,  copper  and  zinc, 
are  surrounded  by  electrolytes,  the  tendency  of  which  is  to  pass 
toward  the  opposite  pole.  Thus,  the  positive  ions,  Cu  and  H,  progress 
toward  the  cathode,  while  the  negative  OH  and  SO4  pass  toward  the 
anode  which,  inside  the  cell,  is  the  zinc.  The  copper  plate  then  be- 
comes covered  with  bubbles  of  hydrogen  which  finally  place  so  high  a 
resistance  in  the  path  of  the  current  that 
it  is  neutralized  and  ceases  to  flow.  This 
action  which  is  called  polarization,  finally 
leads  to  the  production  of  secondary 
currents,  the  direction  of  which  is  oppo- 
site to  that  of  the  primary  one.  Ifc  may 
also  happen  that  some  of  the  sulphate 
of  zinc  is  attacked  by  the  hydrogen  and 
is  deposited  upon  the  copper  plate  in  the 
form  of  a  film  of  constantly  increasing 
thickness.  This  action  must  necessarily 
lead  to  a  reduction  of  the  electromotive 
force  and  finally  to  a  cessation  of  the  pri- 
mary current.  In  the  Daniell  cell,  the 
occurrence  of  polarization  is  prevented 
by  the  copper  sulphate  and  in  the 
Leclanche  cell  by  the  dioxid  of  man- 
ganese. 


Fig.   29. — Non-polahizable 

Electrodes. 

M,  muscle  or  nerve;  C,  cotton 

or  camel's  hair  brush;  S,  solution 

of  zinc  sulphate;  Z,  amalgamated 

zinc. 


Under  ordinary  conditions  the  electrical  cur- 
rent is  passed  through  living  substance  by  means 
of  two  copper  wires  which  may  be  equipped 
with  small  platelets  of  platinum.  In  order 
to  lessen  the  resistance,  these  points  of  contact 
should  be  covered  with  cotton  moistened  with 

saline  solution.  If  applied  for  a  considerable  length  of  time,  these  metal  elec- 
trodes become  covered  with  the  products  of  the  electrolysis  resulting  ia  the  course 
of  the  passage  of  the  electrical  current  through  this  moist  conductor,  formed  by 
the  muscle  and  nerve  tissue.  Thus,  if  a  current  is  conducted  through  water,  a 
film  of  bubbles  of  oxj-gen  eventually  accumulates  upon  the  platinum  of  the 
positive  pole,  while  the  negative  pole  becomes  covered  with  hydrogen.  Presently, 
the  latter  assumes  a  positive  change  and  gives  rise  to  a  current  which  passes  in  a 
direction  opposite  to  that  of  the  original  current.  The  final  outcome  of  this  is  a 
neutralization  of  the  primary  difference  in  potential.  This  polarization  of  the 
electrodes  may  be  avoided  by  using  so-called  non-polarizable  electrodes.  Those 
devised  by  Du-Boid-Raymond  consist  of  zinc  terminals  immersed  in  a  solution 
of  zinc  sulphate.  A  very  simple  form  may  be  made  by  taking  two  pieces  of 
curved  glass  tubing,  measuring  4  mm.  in  diameter  and  about  6  cm.  in  length. 
The  lower  end  of  each  tube  is  filled  with  modelling  clay  or  kaolin  moistened  with 
normal  saline  solution.     The  remaining  space  in  each  tube  is  filled  with  a  satu- 


60 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


rated  solution  of  sulphate  of  zinc  into  which  is  placed  a  short  rod  of  amalga- 
mated zinc  carrying  the  end  of  the  copper  wire.  At  their  points  of  contact  with 
the  muscle  or  nerve  a  small  tuft  of  cotton  should  be  placed  which  has  been 
thoroughly  inoistened  with  saline  solution.  These  electrodes  must  be  carefully 
washed  after  each  experiment  and  must  always  be  kept  in  saline  solution  for  several 
hours  before  they  are  used  in  order  to  render  the  clay  completely  permeable. 
Polarization  is  impossible  in  this  case,  because  at  the  junction  of  the  cathodal  metal- 
lic zinc  with  the  liquid  conductor  ZnS04,  the  cation  Zn  deposits  itself  upon  the  zinc 
electrode  and  does  not  act  upon  the  water  to  liberate  hydrogen  gas.  In  quite  the 
same  way,  the  anode  is  kept  free,  because  there  the  sulphion  SO4  does  not  attack 
the  water  but  the  zinc,  forming  ZnS04. 

The  Making  and  Breaking  of  the  Current. — The  electrodes  are 
always  permitted  to  remain  in  contact  with  the  muscle-nerve  prep- 
aration, while  the  making  and  breaking  of  the  current  is  accomplished 


Fig.  30. — The   Making  and  Breaking  of  the  Current  by  Means  of  a  DuBois- 

Reymond  Key  (K). 

by  the  closing  and  opening  of  a  key  or  switch,  interposed  between  the 
positive  pole  of  the  battery  and  the  positive  electrode.  The  DuBois- 
Reymond  key  consists  of  two  bars  of  brass  connected  by  a  rocking 
plate.  If  arranged  as  is  shown  in  figure  30 A,  the  current  is  made  to 
pass  through  the  muscle  by  closing  this  bridge,  while  its  opening 
breaks  the  circuit.  If  arranged  as  is  represented  in  figure  SOB,  the 
bridge  remains  down  to  begin  with.  The  current  then  flows  from  the 
anode  to  the  cathode  of  the  battery  through  the  key  and  does  not 
reach  the  muscle  at  all,  because  the  resistance  offered  by  the  tissue 
between  the  points  of  contact  of  the  electrodes,  is  very  much  greater 
than  that  resident  in  the  brass  bridge.  Conversely,  if  the  key  is 
raised,  the  current  must  seek  its  level  by  way  of  the  longer  course 
through  the  muscle,  while  its  closure  again  permits  the  current  to 
seek  the  battery  by  following  the  path  of  least  resistance  through  the 
brass  bridge.     By  the  latter  procedure  the  current  is  short-circuited. 


GRAPHIC    REGISTRATION    OF    MUSCULAR    CONTRACTION         Gl 

In  many  cases  it  matters  little  which  way  this  friction  key  is  ad- 
justed. Under  certain  conditions,  however,  it  is  desirable  to  stimulate 
while  the  current  is  already  under  way  and  in  closest  proxhnity  to  the 
muscle  (B)  rather  than  that  it  must  first  expend  a  certain  amount 
of  its  initial  energy  in  passing  all  the  way  from  the  battery  to  the 
preparation  (A).  Furthermore,  if  adjustment  B  is  employed,  the 
muscle  does  not  remain  in  direct  connection  with  the  battery,  while 
in  A  it  remains  in  contact  with  the  positive  pole  as  long  as  the  key 
is  kept  open.  This  arrangement  may  at  times  give  rise  to  unipolar 
stimulation.     Many    other   forms    of   keys    have    been    devised.     A 


Fig.  31. — Pohl  Commutator. 
By  moving  the  bridge  B  in  the  manner  here  indicated  the  current  maj'  be  reversed 
at  the  preparation  M.     The  cross-bar  of  the  bridge  is  insulated. 

very  convenient  one  has  been  described  by  Morse.  The  current  is 
made  by  pressing  upon  a  lever  which  is  again  forced  upw^ard  by  a 
spring  as  soon  as  it  is  no  longer  pressed  upon.  In  the  mercury  key, 
contact  is  made  by  dipping  the  pointed  end  of  the  bridge  into  a 
small  porcelain  cup  filled  with  mercury. 

Commutators  or  pole-changers,  such  as  have  been  devised  by  Pohl,  are  some- 
times inserted  in  the  circuit  in  order  to  be  able  to  divert  the  current  alternately 
into  two  sets  of  electrodes  and  also  to  reverse  its  direction.  A  very  useful  type  of 
pole  changer  consists  of  a  round  block  of  wood  containing  six  depressions  filled 
with  mercury.  The  wires  from  the  battery  are  connected  with  the  two  central 
cups  situated  upon  the  opposite  sides  of  the  block.  The.se  cups  contain  the  sup- 
ports of  a  double  rocking  bridge  which  may  be  adjusted  in  such  a  w'ay  that  the 
current  is  diverted  into  the  wires  leading  off  from  either  pair  of  outside  cups,  or  is 
reversed  by  directing  it  across  the  central  connections  (Fig.  31). 


62  PHYSIOLOGY    OF   MUSCLE    AND    NERVE 

Different  Types  of  Current. — If  the  two  poles  of  a  Voltaic  battery 
are  connected  with  one  another  by  wires  and  a  simple  key,  the  current 
begins  to  flow  as  soon  as  the  bridge  is  closed  and  ceases  to  flow  as  soon 
as  it  is  opened.  Moreover,  provided  that  the  electromotive  force 
land  the  resistance  remain  the  same,  the  current  must  retain  a  definite 
strength  or  volume  from  its  make  to  its  break.  A  current  of  this  kind 
is  characterized  as  a  constant  or  galvanic  current.  It  must  be  kept  in 
mind,  however,  that  the  flow  of  an  electrical  current  is  not  identical 
with  that  of  water  through  a  pipe,  but  consists  merely  of  a  transfer  of 
energy  in  the  form  of  electricity.  The  nature  of  this  force  is  not 
known. 

In  1831,  Faraday  wound  two  coils  of  insulated  wire  around  a  ring 
of  iron,  the  ends  of  which  he  connected  with  a  galvanometer.  On 
passing  a  galvanic  current  through  the  iron,  he  found  that  the  needle 
of  the  galvanometer  was  deflected  first  on  the  make  and  again  on  the 
break  of  this  current.  This  deflection  was  only  of  momentary  dura- 
tion, but  clearly  proved  that  the  primary  current  also  produced  a 
current  in  the  second  closed  circuit  of  wires.  Peculiarly  enough,  the 
secondary  current  appeared  only  at  the  very  moment  when  the  bat- 
tery current  was  made  and  broken.  He  obtained  very  similar  results 
with  coils  placed  next  to  one  another  on  wooden  cylinders  and  also 
with  the  aid  of  a  magnet  surrounded  by  a  coil  of  wire.  A  current 
which  is  produced  in  a  closed  secondary  circuit  whenever  the  current 
flowing  through  a  neighboring  primary  circuit  is  made  or  broken,  is 
called  an  induced  current.  Inasmuch  as  this  induction  may  be  re- 
peated either  at  longer  intervals  or  in  very  rapid  succession,  we  recog- 
nize single  as  well  as  quickly  repeated  induction  shocks.  The  former 
represent  widely  separated  make  and  break  shocks,  while  the  latter 
are  made  to  follow  one  another  in  such  rapid  succession  that  they  give 
rise  to  an  almost  constant  flow  of  stimuli.  The  latter  constitute  the 
so-called  "tetanic"  current. 

The  Induction  Coil. — The  induction  apparatus  devised  by  DuBois- 
Reymond,  consists  of  a  spiral  of  about  130  coils  of  insulated  copper 
wire  of  medium  thickness,  the  ends  of  which  are  connected  through  a 
key  with  the  two  elements  of  a  battery.  These  connections  form  the 
primary  circuit.  The  core  inside  the  primary  coil  is  filled  with  a 
bundle  of  straight  pieces  of  thin  iron  wire  coated  with  shellac.  A  sec- 
ond spiral  containing  about  6000  coils  of  insulated  copper  wire  of  a 
thickness  of  0.1  mm.,  is  placed  around  the  primary  coil  in  such  a  way 
that  it  may  be  pushed  completely  over  it  or  farther  away  from  it. 
The  two  ends  of  this  secondary  coil  are  continued  onward  to  the  elec- 
trodes.    These  connections  form  the  secondary  circuit. 

At  the  very  moment  when  the  primary  current  is  made,  a  current  is  also  set  up 
for  a  brief  period  of  time  in  the  secondarj^  circuit.  It  should  be  emphasized,  how- 
ever, that  this  secondary  current  is  merely  induced,  and  is  therefore  absolutely  in- 
dependent of  the  primary  current.  This  fact  may  be  made  more  evident  by  plac- 
ing the  secondary  coil  at  some  distance  from  the  primarj^  so  that  there  is  an  empty 


GRAPHIC   REGISTRATION    OF   MUSCULAR    CONTRACTION 


63 


space  between  tluMii.  A  siinihir  iiuluction  is  developed  when  the  primary  current 
is  broken.  During  the  interim,  however,  there  is  no  induction  in  spite  of  the  fact 
that  the  current  in  the  primary  coil  continues  without  interruption. 

If  the  direction  of  the  induced  current  is  now  determined  by  means  of  a  gal- 
vanometer, it  is  found  that  the  making  induction  shock  is  opposed  to  the  primary 
current,  wliile  the  breaking  induction  shock  possesses  the  same  direction  as  the 
primary  current.  It  should  also  be  emphasized  that  the  make  induction  develops 
more  slowly  than  the  break  induction.     This  difference  is  due  to  the  fact  that  the 


Fig.  32. — The  Inductorium  (DuBois-Reymond). 
A,  primary  coil;    B,   secondary  coil;  P',  binding  posts  for  wires  from  battery;  p" 
binding  posts  for  wires  leading  to  stimulating  electrodes.      (Howell.) 

entering  jirimary  c^^irrent  must  first  of  all  overcome  the  self-induction  of  the  primary 
coil  before  it  can  produce  its  characteristic  effect  in  the  secondary  coil.  While  it 
passes  from  segment  to  segment  of  the  primary  wire,  an  induced  current  is  momen- 
tarily set  up  in  the  more  distant  stretch  of  wire  which  pursues  a  direction  opposite 
to  it  and  tends  therefore  to  lessen  its  strength.  Until  this  resistance  has  been  over- 
come, it  cannot  possibly  exert  its  full  energy  upon  the  secondary  circuit.  On  the 
break,  however,  this  hindrance  is  not  present,  so  that  the  induction  in  the  secondary 
coil  can  reach  its  ma.ximum  with  much  greater  rapidity.     For  this  reason,  the  break 


Fig.  33. — The  Inductorium. 
/,  primary  circuit  and  coil;  //,  secondary  coil  and  circuit;  K,  key;  ./,  automatic 
interrupter;  A^,  nerve. 


shock  always  stimulates  living  substance  more  intensely  than  the  make  shock. 
The  constant  current,  on  the  other  hand,  stimulates  more  on  the  make,  i.e.,  at 
the  time  when  it  first  enters  the  living  substance  with  its  initial  amplitude. 

The  strength  of  the  induction  shocks  depends  first  of  all  upon  the  strength  of 
the  primary  current  and  therefore  also  upon  the  strength  of  the  battery.  In  the 
second  place,  it  is  proportional  to  the  distance  between  the  two  coils,  i.e.,  it  be- 
comes the  weaker,  the  farther  the  secondary  coil  is  removed  from  the  primary. 
Thus,  we  generally  estimate  the  strength  of  an  induction  shock  by  determining  the 


64 


PHYSIOLOGY    OF   MUSCLE    AND    NERVE 


distance  of  the  coils  in  centimeters  in  conjunction  with  the  strength  of  the  cells  in 
volts. ^  It  need  scarcely  be  mentioned  that  the  induction  may  also  be  diminished 
by  placing  the  secondary  coil  at  an  oblique  angle  to  the  primarj%  AMien  at  right 
angles  to  one  another,  the  secondary  current  fails  to  develop. 

The  primary  current  may  be  made  and  broken  at  different  intervals,  an  induc- 
tion resulting  each  time,  ^^^len  interrupted  very  rapidh^,  the  inductions  in  the 
secondary  circuit  follow  one  another  in  such  quick  succession  that  they  are  fre- 
quently designated  as  a.faradic  or  tetanic  current.  In  order  to  avoid  in  the  latter 
case  the  opening  and  closing  of  the  key  with  the  hand,  an  interrupter  has  been 
provided  which  automatically  makes  and  breaks  the  primary  current.  The  one 
devised  by  Xeef  consists  of  a  \'ibrating  steel  rod  ( T')  and  a  magnet  {E) .     The  current 


Fig.  3-4. — The  Automatic  Interrupter  of  the  Inductoriuai  (Neef's). 
A,  entrance  of  current  from  battery  into  post  B  and  vibrator  T'  as  far  as  D.  In 
accordance  with  the  position  of  the  vibrating  plate,  the  current  now  flows  either  back  to 
the  batterj'  C  through  post  F  or  into  the  primary  coil  PC  through  D.  In  the  latter 
case,  the  current  first  traverses  magnet  E  before  it  can  reach  the  battery  by  way  of 
post  F. 


from  the  battery  (.4.)  is  led  into  the  pillar  B  as  far  as  the  platinum  contact  (D) 
upon  the  vibrator.  If  the  latter  is  in  contact  with  the  end  of  the  wire  of  the  pri- 
mary coil  {PC)  at  D,  the  current  traverses  this  spiral  and  returns  to  pillar  F  and 
the  battery  (C)  by  waj'  of  a  double  spiral  {E) .  But  as  the  current  passes  through 
spirals  E,  their  iron  cores  are  magnetized  and  attract  the  iron  plate  H  of  the 
\dbrator,  thus  breaking  the  contact  of  the  vibrator  at  D.  The  current  then 
flows  directly  into  F  and  back  to  the  battery  (C)  by  way  of  contact  K.  When 
the  primary  current  is  broken  in  this  waj',  the  spirals  {E)  are  again  demagnetized. 
The  iron  plate  {H)  being  released,  the  vibrating  rod  moves  upward  and  again  makes 
contact  at  D.  At  the  very  moment  when  the  primary  current  is  thus  made  and 
broken,  an  induced  current  is  developed  in  the  secondary  coil  which,  however,  ia 
not  shown  in  figure  34. 

^  Martin,  Am.  Jour,  of  Physiol.,  xx^'iii,  1911,  49. 


PECULIARITIES    OF   MUSCLE    TISSUE 


65 


CHAPTER  V 
PECULIARITIES  OF  MUSCLE  TISSUE 

Extensibility  and  Elasticity  of  Muscle. — If  a  rubber  band  is  suc- 
cessively loatled  with  a  number  of  small  weights,  it  suffers  an  extension 
each  time.  The  height  of  these  extensions  remains  the  same  through- 
out this  test  and  is  proportional  to  the  load  applied.  If  the  weights 
are  then  removed  one  by  one,  the  rubber  band  again  shortens  and 
eventually  assumes  its  original  length.  If  a  muscle,  such  as  the 
gastrocnemius,  is  successively  extended  by  a  limited  number  of  weights 
of  10  grams  each,  it  is  found  that  the  extensions  are  greatest  directly 
after    the    application  of    the  weight  and  then  gradually  decrease^ 


/ 


Fig.  35. — Extensibility  and  Elasticity. 
^4.,  rubber  band  and  B,  gastrocnemius  muscle  of  frog  successively  loaded  with  10 
gram  weights.     The  second  curve  shows  a  decreasing  extension  for  equal  increments, 
hence,  the  line  joining  the  end  of  the  ordinates  is  curved. 

(Fig.  355).  But  naturally,  each  weight  must  be  permitted  to  act 
for  a  moderate  length  of  time,  because  the  muscle  substance  is  viscous 
and  yields  only  slowly  to  the  strain.  If  the  weights  are  now  removed 
one  by  one,  the  muscle  again  shortens,  but  does  not  attain  its  former 
length.  Its  detension,  therefore,  is  imperfect  and  hence,  the  excised 
muscle  must  be  regarded  as  being  incompletely  elastic.  Its  behavior 
is  similar  to  that  of  other  organic  bodies.'  While  in  its  normal  posi- 
tion in  the  body,  its  elastic  power  is  of  course  absolute,  so  long  as  it  is 
not  acted  upon  by  excessive  weights. 

If  the  weights  are  added  continuously,  the  elastic  power  of  the 
muscle  is  eventually  overcome.  Beginning  at  this  point,  its  extension 
occurs  with  great  rapidity  until  it  tears.  In  the  case  of  the  sartorius 
muscle,  this  breaking  point  lies  at  500  grams  and  in  the  case  of  the 
gastrocnemius  at  about  750  grams.  From  these  figures  it  may 
readily  be  gathered  that  the  strain  which  such  small  masses  of  muscle 

1  Dreser,  Archiv  fiir  Exp.  Path.  u.  Pharm.,  xxvii,  1890,  51. 
^  Brodie,  Jour,  of  Anat.  and  Physiol.,  xxix,  1895,  367;  and  Haj-croft,  Jour,  of 
Physiol.,  xxxi,  1904,  392. 


66  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

tissue  are  capable  of  withstanding,  is  astonishingly  great.  To  begin 
with,  therefore,  the  successive  application  of  these  weights  gives  rise 
to  a  curve,  the  concavity  of  which  is  turned  toward  the  abscissa, 
while  eventually,  when  the  elasticity  of  the  muscle  has  been  overcome, 
it  is  turned  downward.  Dead  muscle  is  less  extensible  than  living 
muscle,  whereas  contracted  or  fatigued  muscles  are  more  extensible. 

The  elastic  power  of  muscle  tissue  serves  as  a  protection  against 
injury  by  sudden  counter  forces.  Especially  in  the  case  of  the  striated 
type,  it  minimizes  the  possibility  of  damage  to  the  bones  and  tendons. 
Furthermore,  this  elastic  tension  prevents  the  muscles  from  relaxing 
completely  so  that  they  are  always  held  in  a  condition  of  "setting" 
which  enables  them  to  react  more  promptly  as  well  as  more  smoothly. 
It  serves,  therefore,  to  conserve  the  energy  which  is  required  to  produce 
a  contraction.  In  many  cases,  the  skeletal  muscles  are  arranged 
antagonistically  to  one  another,  so  that  the  contraction  of  one  set  places 
the  others  under  a  certain  elastic  tension.  This  is  especially  true  of  the 
flexors  and  extensors  of  the  arms.  Elastic  forces  also  play  a  most 
important  part  in  the  production  of  the  pressure  which  is  required  to 
drive  the  blood  through  the  circulatory  system.  In  this  particular 
instance,  however,  this  function  is  assigned  to  the  elastic  tissue  of  the 
blood-vessels  rather  than  to  the  smooth  muscle  cells.  Cardiac  muscle 
exhibits  its  elastic  power  most  clearly  at  the  beginning  of  ventricular 
systole,  i.e.,  directly  after  the  ventricular  wall  has  been  fully  distended 
by  the  forcible  emptying  of  the  auricles. 

Tonicity  of  Muscle. — A  normal  muscle,  when  resting,  is  not  re- 
tained in  a  condition  of  complete  relaxation,  but  is  held  in  a  state  of  the 
slightest  possible  contraction.  The  factor  which  is  chiefly  responsible 
for  this  tonic  setting  of  a  muscle  is  the  elastic  tension  of  its  constituents. 
Thus  we  find  that  the  division  of  one  sciatic  nerve  causes  the  cor- 
responding leg  to  hang  down  much  lower  than  that  of  the  opposite  side, 
because  its  muscles  have  now  entered  a  state  of  complete  relaxation. 
It  should  be  noted,  however,  that  the  tension  of  the  muscles  does  not 
constitute  the  condition  of  tonus,  but  is  merely  one  of  the  prerequisites 
thereof.  Tonus  in  reality  is  the  result  of  a  continuous  influx  of  im- 
pulses from  the  central  nervous  system. 

In  further  analysis  of  this  phenomenon  it  will  be  found  that 
ganglion  cells  and  their  efferent  adjuncts  retain  their  function  only 
if  allowed  to  remain  in  contact  with  those  sense  organs  which  keep 
them  in  activity  by  means  of  their  centripetal  impulses.  If  these 
impulses  are  prevented  from  reaching  the  center,  the  corresponding 
effector  becomes  inactive  and  loses  its  tonus.  So  it  is  with  muscle. 
It  cannot  be  said,  therefore,  that  the  cells  of  the  spinal  cord  are  auto- 
matically concerned  with  the  production  of  tonus,  because  their 
activity,  and  hence  also  the  tonus  of  the  muscles  innervated  by  them, 
disappears  very  promptly  after  the  dorsal  roots  of  the  spinal  nerves 
have  been  divided.  It  will  be  remembered  that  these  paths  serve  as 
highways  for  a  large  number  of  afferent  impulses.     Their  destruction, 


PECULIARITIES    OF   MUSCLE    TISSUE  67 

therefore,  must  give  rise  to  a  loss  of  stimulation  and  tonus.  Afferent 
impulses  may  come  from  the  skin  and  subcutaneous  tissue  as  well  as 
from  the  muscles  themselves;  in  fact,  they  may  also  arise  in  higher 
centers.  Concerning  tiiose  arising  in  the  muscles  themselves,  it  may 
be  stated  at  this  time  that  the  division  of  the  afferent  path  of  a  muscle, 
or  groups  of  muscles,  is  generally  followed  by  a  considerable  loss  of 
their  tonus.  It  seems,  therefore,  that  the  so-called  musckvsense  has 
much  to  do  with  this  phenomenon.  Th(;  pressure  exerted  by  the  con- 
tracting fibers  upon  the  muscle-spindles,  sets  up  certain  afferent  im- 
pulses which  are  eventually  relayed  to  the  effector,  and  keep  the  latter 
in  a  condition  of  functional  alertness.  In  last  analysis,  therefore,  the 
tonus  of  muscle  must  be  regarded  as  a  reflex  phenomenon. 

The  Trophic  State  of  Muscle. — The  anatomical  and  functional 
integrity  of  a  muscle  can  only  be  retained  if  it  is  subjected  to  frequently 
repeated  stimulations.  In  case  the  latter  cease  at  any  time,  say,  in 
consequence  of  the  severance  of  the  path  by  means  of  which  the  mus- 
cle is  connected  with  the  central  nervous  system,  it  undergoes  retro- 
gressive changes  and  finally  loses  its  functional  usefulness  entirely. 
This  atrophic  state  is  ushered  in  by  a  diminution  in  its  irritability, 
lasting  a  number  of  days.  Subsequent  to  this  period  its  irritability 
again  increases  and  remains  high  for  several  weeks  until  it  is  abolished 
altogether.  During  the  second  phase  the  muscle  is  prone  to  exhibit 
irregular  contractions  which  remain  confined  to  certain  groups  of  its 
fibers  and  impart  a  peculiar  fibrillary  motion  to  its  substance  as  a 
whole.  Peculiarly  enough,  this  degeneration  may  be  arrested  at  any 
time  by  reuniting  the  ends  of  the  cut  nerve.  The  muscle  then  grad- 
ually recovers  and  regains  its  normal  trophic  condition  in  the  course 
of  time.  During  the  interim  the  muscle  may  in  a  measure  be  pre- 
vented from  losing  its  function  altogether  by  stimulating  it  artifically 
through  the  integument. 

It  must  be  evident,  therefore,  that  the  metabolism  of  a  muscle  is 
absolutely  dependent  upon  its  connection  with  the  central  nervous 
system.  For  this  reason,  it  is  commonly  held  that  the  ganglion  cells 
exert  a  trophic  influence  upon  the  muscle,  which,  however,  is  brought  to 
bear  upon  it  through  its  ordinary  motor  nerve  and  not  through  special 
trophic  fibers.  Hence,  any  motor  nerve  may  be  said  to  possess  trophic 
qualities,  because  it  keeps  the  muscle  in  activity,  thereby  favoring  its 
metabolic  processes.  The  blood  supply  is,  of  course,  of  some  impor- 
tance, because  a  copious  flushing  out  of  the  muscle  retards  the  process 
of  degeneration,  while  a  scanty  blood  supply  greatly  favors  the  occur- 
rence of  these  changes.  This  fact  is  demonstrated  in  a  convincing 
manner  by  Stenson's  experiment.  If  the  abdominal  aorta  of  a  rabbit 
is  ligated,  the  muscles  of  the  posterior  extremity  soon  lose  their  irri- 
tability, owing  to  the  decrease  in  the  supply  of  oxygen  and  other 
nutritive  material.  Upon  releasing  the  compression  their  func- 
tion reappears  very  quickly.  The  same  results  may  be  obtained 
by  perfusing   them    with   venous    blood    or   by  retarding   the    flow 


68 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


until  the  venous  blood  has  acquired  considerable  anounts  of  carbon 
dioxid. 

The  Wave  of  Contraction. — A  long  muscle  generally  receives  its 
nerve  fibers  from  a  place  about  midway  between  its  two  ends,  while 
a  short  and  compact  muscle  usually  receives  them  at  its  upper  pole. 
It  is  of  course  essential  that  its  constituent  fibers  contract  at  about  the 
same  time,  otherwise  the  best  mechanical  results  cannot  be  obtained. 
For  this  reason,  the  nerve  terminals  are  commonly  distributed  in  such 
a  way  that  the  impulses  reach  the  individual  fibers  at  about  the  same 
time  and  produce,  therefore,  a  contraction  which,  to  all  appearances, 
occurs    practically  simultaneously  throughout  the  muscle. 

It  can  easily  be  shown,  however,  that  the  contraction  of  striated 
muscle  starts  at  the  point  stimulated  and  progresses  from  here  to  its 


Fig.  36. — The  Wave  of  Coxtractiox. 
M,  sartorius  muscle  of  frog,  A  and  B,  two  levers  placed  horizontally  upon  muscle; 
S,  stimulating  electrodes;  T,  time;  K,  kymograph.      When  stimulated  at  S,  lever  A  ia 
raised  first. 


more  distant  segments.  Thus,  if  the  sartorius  muscle  of  a  frog,  or  one 
of  the  long  muscles  of  the  neck  of  a  turtle,  is  placed  flat  upon  a  board 
with  two  writing  levers  resting  horizontally  upon  its  two  ends,  a  stimu- 
lus applied  to  one  of  its  ends  first  of  all  produces  a  rise  of  that  lever 
which  hes  nearest  the  seat  of  the  stimulation  (Fig.  36).  No  special 
record  of  the  time  need  be  taken,  because  the  interval  between  the 
contractions  of  the  two  poles  of  the  muscle  is  quite  apparent  even 
without  this.  It  is  advisable,  however,  to  curarize  the  muscle  before- 
hand so  that  the  wave  of  excitation  cannot  be  spread  by  means  of  the 
intra-muscular  nerve  fibers.  From  this  fact  it  may  be  deduced  that 
the  contraction  travels  over  muscle  in  the  form  of  a  wave  possessing  a 
definite  velocity.  If  the  distance  between  the  two  levers  is  compared 
with  the  difference  in  the  time  between  the  two  contractions,  the  speed 
with  which  this  wave  is  pi'opagated,  can  easily  be  determined.     Ac- 


PECULIARITIES    OF   MUSCLE    TISSUE  69 

cording  to  Rollctt  and  Engelmann,  it  amounts  to  3-5  m.  per  second 
in  cold-blooded  animals,  and  to  6  m.  per  second  in  warm-blooded 
animals.  For  human  muscle  the  value  of  10-13  m.  in  a  second  has 
been  given.  The  removal  of  the  muscle  from  the  body,  cooling  or 
fatiguing  it,  and  other  factors,  tend  to  diminish  the  speed  of  this  wave. 
It  is  independent  of  the  strength  of  the  stimulus. 

Very  characteristic  progressive  contractions  of  muscle  are  also 
exhibited  by  the  stomach,  intestine  and  ureter,  but  naturally,  we  are 
dealing  in  these  cases  with  smooth  muscle  which  gives  the  so-called 
peristaltic  wave.  This  form  of  contraction  is  produced  by  the  inter- 
action of  the  circular  and  longitudinal  fibers,  and  although  regulated 
by  a  nervous  mechanism  in  most  cases,  this  regulation  is  not  absolutely 
essential,  as  may  be  gathered  from  the  observation  that  the  upper  por- 
tion of  the  ureter  contracts  with  perfect  precision  although  it  contains 
no  nervous  elements.  The  same  may  be  said  regarding  excised  seg- 
ments of  arteries.  The  contraction  of  the  heart  is  also  described  as 
wave-like,  the  auricles  contracting  first  and  the  ventricles  last,  and 
both  in  a  direction  from  base  to  apex.  Even  excised  pieces  of  cardiac 
muscle  exhibit  this  wave-like  manner  of  contraction,  as  may  be  shown 
by  converting  the  ventricle  of  a  frog  into  a  zigzag  strip  by  several  trans- 
verse incisions  and  stimulating  this  preparation  either  at  its  base  or 
at  its  apex.  The  contraction  will  then  be  seen  to  progress  from  the 
area  stimulated  to  the  opposite  end  of  the  strip. 

The  Muscle  Sound. — If  a  stethoscope  is  applied  over  a  contracting 
muscle,  such  as  the  biceps,  a  low  rumbling  sound  is  heard,  ^  corres- 
ponding to  a  frequency  of  30-40  vibrations  to  the  second.  A  sound 
is  also  produced  by  the  contracting  masseter  muscle  which  may  be 
rendered  audible  by  placing  the  side  of  the  face  flat  against  a  receiving 
body  or  by  shutting  the  ears  with  the  index  fingers. ^  Helmholtz^  has 
called  attention  to  the  fact  that  this  sound  corresponds  in  reality  to 
the  resonance  sound  of  the  external  ear.  By  determining  its  pitch  with 
the  help  of  different  vibrating  reeds  held  in  contact  with  the  con- 
tracting muscle,  he  came  to  the  conclusion  that  it  is  chiefly  constituted 
by  the  first  overtone  of  a  sound  possessing  a  frequency  of  vibration 
of  18-20  in  a  second.  Two  very  characteristic  sounds  are  also  pro- 
duced by  the  contracting  ventricle  of  the  heart,  of  which  the  first  is 
almost  entirely  muscular.  Even  excised  pieces  of  ventricle  emit  a 
sound. 

1  Discovered  bj^  WoUaston  and  Erman  90  years  ago. 
^  Stem,  Pfliiger's  Archiv,  Ixxxii,  1900,  34. 
3  Wissensch.   Abhandl.,  ii,  928. 


70  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


CHAPTER  YI 
THE  CHARACTER  OF  THE  CONTRACTION  OF  MUSCLE 

The  Simple  Twitch. — In  accordance  with  the  frequency  and  char- 
acter of  the  stimulus,  striated  muscle  reacts  by  giving  either  a  simple 
twitch-Uke  contraction  or  a  prolonged  contraction,  known  as  tetanus. 
The  former  is  obtained  whenever  the  muscle  or  its  motor  nerve  is 
excited  with  a  single  stimulus,  whether  it  be  mechanical,  electrical, 
thermal  or  chemical.  A  graphic  record  of  it  maj'  be  made  by  con- 
necting the  muscle  with  a  writing  lever  in  the  manner  described 
previously.  If  the  kymograph  is  permitted  to  remain  stationary,  the 
contracting  muscle  registers  merel}'  a  straight  line  approaching  the 


Fig.  37. — A  AIuscle  Twitch. 
M,  make  shock  recorded  by  magnetic  signal  connected  with  primary  circuit.     Time 
in  ^f  00  sec. ;  L,  latent  period ;  C,  period  of  contraction ;  7?,  period  of  relaxation. 

vertical,  whereas  a  revolving  kymograph  will  tend  to  separate  the  up 
and  down  strokes  more  and  more  as  its  speed  is  increased.  The  result 
is  a  wave-hke  curve,  possessing  a  certain  height  and  length.  A  tuning 
fork,  carrying  a  marker  upon  one  of  its  prongs,  is  usually  permitted  to 
register  its  vibrations  below  the  writing  lever  of  the  muscle.  More- 
over, if  the  electrical  method  of  stimulation  is  employed,  the  moment 
at  which  the  shock  is  thrown  into  the  muscle  or  its  nerve,  may  be 
registered  by  means  of  an  electro-magnetic  signal  which  is  inserted  in 
the  primary  circuit  and  is  permitted  to  write  in  the  same  ordinate  as 
the  other  levers. 

If  a  muscle-curve  of  this  kind  is  studied  in  detail,  it  is  seen  to  con- 
sist of  two  principal  phases,  namely  a  period  of  contraction  and  a  period 
of  relaxation.  During  the  former  the  muscle  shortens  until  it  has 
attained  its  state  of  maximal  contraction,  while  during  the  latter  it 
relaxes  until  it  has  again  reached  its  natural  length  and  form.  If  a 
comparison  is  now  made  between  this  curve  and  the  record  of  the  signal 


THE  CHARACTER  OF  THE  CONTRACTION  OF  MUSCLE    71 

and  that  of  the  tuning-fork,  it  will  be  found  that  the  muscle  does  not 
begin  to  contract  precisely  when  the  shock  is  passed  into  it,  but  a 
moment  thereafter.  This  period,  intervening  between  the  application 
of  the  stimulus  and  the  reaction,  is  designated  as  the  latent  period. 
Hence,  a  muscle  curve  really  presents  three  phases,  namely  a  latent 
period,  a  period  of  contraction  and  a  period  of  relaxation.  No  visible 
mechanical  energy  is  liberated  during  the  first,  because  it  is  occupied 
solely  by  various  changes  anteceding  the  actual  contraction. 

If  the  indirect  method  of  stimulation  is  employed,  it  may  be 
thought  that  a  large  part  of  the  latent  period  is  consumed  in  the  pas- 
sage of  the  nerve  impulse  to  the  muscle.  This  contention,  however, 
cannot  be  considered  of  much  value,  because  the  shifting  of  the  elec- 
trodes to  a  place  very  close  to  the  muscle  does  not  materially  shorten 
this  interval,  nor  does  their  removal  to  a  more  distant  point  give  rise 
to  an  appreciable  lengthening.  It  must  be  evident,  therefore,  that  the 
conduction  of  the  impulse  over  the  nerve  consumes  only  the  briefest 
possible  time  and  that  by  far  the  greatest  part  of  the  latent  period  is 
consumed  in  initiating  those  changes  which  finally  bring  the  mech- 
anism of  contraction  into  play. 

As  far  as  the  time  relationship  between  these  periods  is  concerned, 
it  should  be  stated  first  of  all  that  the  duration  of  a  simple  contraction 
of  muscle  is  subject  to  certain  variations  which  depend  upon  the  char- 
acter of  the  muscle  tissue  and  its  condition  at  the  time  of  experimen- 
tation. ^  A  perfectly  fresh  gastrocnemius  muscle  of  the  frog  completes 
its  contraction  in  about  0.1  sec,  of  which  0.01  sec.  is  taken  up  by 
the  latent  period,  0.04  sec.  by  the  contraction  and  0.05  sec.  by  the 
relaxation. 

Summation  and  Fusion  of  Contractions. — If  a  second  shock  is 
sent  into  the  muscle  very  shortly  after  the  beginning  of  its  relaxation 
following  the  first  stimulus,  a  second  contraction  will  be  obtained  which 
is  higher  than  the  first.  This  phenomenon  is  known  as  summation  of 
contractions.  In  quite  the  same  manner,  a  third  contraction  may  be 
added  to  the  second  and  a  fourth  to  the  third,  and  so  on,  until  the 
relaxations  intervening  between  them  become  very  incomplete  and 
the  individual  contractions  are  fused  into  an  incomplete  tetanus.  If 
the  individual  stimuli  are  now  permitted  to  succeed  one  another  so 
rapidly  that-  the  relaxations  cease  to  be  discernible  and  the  curve  as  a 
whole  pursues  a  straight  course,  the  muscle  records  what  is  commonly 
described  as  a  tetanus. 

It  should  be  remembered,  however,  that  the  interval  between  the 
succeeding  shocks  cannot  be  shortened  indefinitely,  because  a  point 
will  eventually  be  reached  when  the  second  stimulus  loses  its  effect- 
tiveness.  This  fact  implies  that  a  certain  period  must  always  be 
allowed  to  intervene  between  the  different  stimulations,  otherwise  the 
muscle  will  be  in  no  condition  to  receive  the  succeeding  stimulus.     In 

1  Schultz,  Archiv  fiir  Anat.  und  Physiol.,  1897,  22;  also  see:  C.  C.  Stewart, 
Am.  Jour,  of  Physiol.,  iv,  1901,  202. 


72  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

other  words,  the  destruction  of  the  myoplasmic  material  must  first  be 
made  good  by  anaboHc  changes  before  the  muscle  can  again  respond. 
This  period  during  which  the  muscle  remains  inexcitable  to  a  second 
stimulus,  is  known  as  the  refractory  period.  Its  duration  is  only  about 
0.0015  sec.     Thus,  a  muscle  is  in  a  position  to  react  to  stimuli  only  if 


Fig.  38. — Summation  of  Contractions. 
M  and  B,  make  and  break  shocks  indicated  by  an  electro-magnetic  signal.     Time 
in  3-100   sec.     As   the   break  contraction  occurs  during  the  period  of  relaxation  of  the 
make  contraction,  it  is  added  to  the  first. 

they  recur  with  a  lesser  frequency  than  one  in  every  0.001 5  sec.  If  their 
rate  is  increased  beyond  this  limit,  not  every  stimulus  will  be  capable 
of  producing  a  reaction.  As  will  be  shown  later,  the  refractory  period 
is  of  especial  functional  significance  in  the  case  of  cardiac   muscle. 


Fig.  39. — Fusion  and  Tetanu.s. 
S,  summation;  F,  fusion;  T,  tetanus.     Time  in  seconds.     The  individual  make  and 
break  shocks  are  repeated  so  quickly  that  a  continuous  contraction  is  obtained. 

Tetanus. — A  tetanic  contraction  of  muscle  exhibits  a  greater 
height  and  length  than  the  simple  twitch.  It  must  be  evident  from  the 
preceding  discussion  that  a  tetanus  is  really  composed  of  a  multi- 
tude of  single  contractions  which  have  been  fused  into  a  continuous 
curve  by  permitting  the  stimuli  to  enter  the  muscle  at  very  brief  in- 


THE  CHARACTER  OF  THE  CONTRACTION  OF  MUSCLE    73 

tervals.  Hence,  the  height  of  a  tetanic  contraction  must  always  ex- 
ceed that  of  a  twitch  and  its  summit  must  be  attained  more  quickly, 
provided,  of  course,  that  the  same  strength  of  stimulus  is  employed  in 
both  cases.  Having  reached  its  maximal  degree  of  shortening,  the 
muscle  remains  in  the  contracted  condition  until  the  stimuli  are  made 
to  cease.  It  need  not  surprise  us,  however,  to  find  that  the  continued 
activity  of  the  muscle  leads  to  a  destruction  of  material  which  eventu- 
ally causes  it  to  become  fatigued.  This  phenomenon  is  indicated 
in  the  curve  by  a  gradual  decline  of  the  lever  which  becomes  the  greater, 
the  longer  the  duration  of  the  stimulation.  Eventually,  therefore,  the 
muscle  must  return  into  the  position  of  complete  relaxation  in  spite 
of  the  continuance  of  the  stimulation.  Under  ordinary  conditions, 
however,  the  stimuH  are  sent  into  a  muscle  only  for  a  relatively  short 
period  of  time,  but  naturally,  even  the  briefest  tetanus  is  longer  than 
a  simple  twitch. 


Fig.  40. — Tetanic  Contractiox. 
Recorded  by  means  of  Neef's  automatic  interrupter.     Time  in  seconds.     The  de- 
cline of  the  curve  is  an  indication  of  fatigue. 

Whether  or  no  a  muscle  will  become  greatly  fatigued  depends,  of 
course,  upon  its  condition  at  the  time  of  experimentation  and  upon 
the  strength  and  duration  of  the  stimulation.  Thus,  an  already 
somewhat  fatigued  muscle  requires  a  much  smaller  number  of  stimuli 
to  be  tetanized  than  one  just  freshly  prepared.  The  same  is  true 
of  a  cooled  muscle  as  against  one  which  is  kept  at  the  temperature 
of  the  room.  It  is  evident,  therefore,  that  the  number  of  stimuli 
which  are  necessary  to  tetanize  a  muscle  completely,  differ  very  widely. 
Ordinarily  a  frog's  gastrocnemius  necessitates  about  20-30  in  a  second, 
and  smooth  muscle  one  in  every  5-7  seconds. 

Voluntary  Contractions. — Inasmuch  as  our  skeletal  muscles  con- 
tract normally  in  consequence  of  an  influx  of  stimuli  from  the  cerebral 
cortex,  their  reactions  may  be  of  almost  any  length,  until  they  are 
finally  cut  short  by  fatigue.  We  have  seen  that  a  frog's  gastrocnemius 
completes  its  contraction  in  about  0.1  second.  Contractions  of  such 
brevity  are  not  given  by  mammalian  muscles,  because  even  such  seem- 
ingly instantaneous  movements  as  the  closure  of  the  eyelids  or  the 
trilling  motion  of  the  fingers,  cannot  be  executed  in  a  shorter  time 


74  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

than  0.5-1.0  second.  In  accordance  with  this  result,  it  is  generally- 
believed  that  our  voluntary  contractions  bear  a  close  resemblance 
to  the  tetanus  of  excised  muscle.  This  would  imply  that  even  our 
briefest  muscular  movements  are  the  result  of  a  series  of  stimuli  sent 
into  the  muscle  at  regular  intervals  during  the  continuance  of  its  con- 
traction. From  this  it  may  be  inferred  in  turn  that  even  the  shortest 
contractions  of  our  muscles  are  composed  of  a  number  of  simple 
twitches.  This  inference  is  strengthened  by  the  observation  that  a 
contracting  muscle  emits  a  sound  which  possesses  a  vibration  frequency 
of  30-40  in  a  second.  This  discontinuity  of  the  contractions  of  our 
skeletal  muscles  is  indicated  further  by  the  curve  recorded  by  our  fin- 
gers when  held  in  voluntary  tetanus.  When  registered  upon  a  slowly 
revolving  drum,  this  curve  invariably  exhibits  irregular  oscillations, 
such  as  occur  in  the  course  of  general  spasms  of  the  musculature 
resulting  from  irritations  of  the  central  ganglion  cells.  Quite  similarly 
it  has  been  shown  by  Piper ^  that  if  a  string-galvanometer  is  applied 
to  the  flexor  muscles  of  the  forearm,  the  stimulation  of  the  median 
nerve  elicits  a  typical  diphasic  deflection  of  the  needle.'  It  was  also 
found  that  the  voluntary  contraction  of  these  muscles  gives  rise  to 
about  40  or  50  of  these  diphasic  variations  in  the  course  of  a  second. 
Other  muscles  gave  similar  results.  By  connecting  this  instrument 
with  the  phrenic  nerve,  Dittler  has  proved  that  the  diaphragm  may 
be  contracted  by  a  discharge  of  impulses  possessing  a  frequency  of 
50  to  70  in  a  second. 

These  results  indicate  very  clearly  that  a  muscle  does  not  contract 
in  consequence  of  the  influx  of  a  single  stimulus,  but  in  consequence  of 
a  series  of  stimuli.  It  must  be  evident,  therefore,  that  the  motor  cells 
innervating  a  muscle  always  discharge  a  series  of  impulses  which  give 
rise  to  a  serial  evolution  of  muscular  energy.  Their  discontinuance 
then  permits  the  relaxation  to  set  in.  The  analogy  between  a  volun- 
tary contraction  and  one  produced  in  excised  muscle  by  artificial 
stimuli,  is  therefore  a  very  close  one.  These  statements  may  also  be 
apphed  to  the  tonus  of  muscle,  with  this  modification,  however,  that 
the  stimuli  upon  which  the  tonic  condition  of  muscle  tissue  depends, 
are  of  subminimal  intensity.  These  rhythmic  discharges  by  the  cen- 
tral ganglion  cells  give  rise  to  a  discontinuous  evolution  of  energy 
which  just  suffices  to  keep  the  muscle  in  a  semi-active  condition,  ready 
to  respond  to  any  supraminimal  stimuli  that  may  impinge  upon  its 
neuromuscular  junction. 

Contracture. — The  term  contracture  signifies  that  the  relaxation 
of  the  previously  contracted  muscle  is  unduly  prolonged,  or,  as  may 
also  be  said,  that  its  contraction  is  maintained  for  an  abnormally 
long  time.  This  condition  is  frequently  encountered  during  fatigue, 
or  when  a  fresh  muscle  is  cooled  or  is  subjected  to  excessive  stimulation. 
It  may  also  be  produced  in  a  chemical  way  by  the  administration  of 
small  doses  of  veratrin  or  barium,  and,  in  a  lesser  degree,  also  by 
iPfluger's  Archiv,  cxix,  1907,  301,  and  Archiv  flir  Physiol.,  1914,  345. 


THE  CHARACTER  OF  THE  CONTRACTION  OF  MUSCLE 


75 


strontium  and  calciuin.  It  is  frequently  associated  with  lesions  of  the 
central  nervous  system,  such  as  give  rise  to  hemiplegia.  It  may  also 
appear  as  a  functional  disorder  in  somnambulism  and  hysteria;  in 
fact,  if  these  conditions  have  persisted  for  sometime,  it  may  happen 
that  entire  groups  of  muscles  remain  permanently  in  an  exaggerated 
tonic  or  contractured  state.  Unless  degenerated,  muscles  of  this  kind 
may  still  be  made  to  give  either  short  twitches  or  tetani.  This  fact 
tends  to  show  that  an  ordinary  contracture  is  different  from  a  tetanus. 
It  represents  merely  a  tonic  setting  or  contraction  of  the  muscle  in 
consequence  of  an  intrinsic  or  extrinsic  excitation  and  may  be  classi- 
fied either  as  functional  or  organic,  in  accordance  with  its  cause  and 
duration. 

Explanations  of  this  phenomenon  have  been  submitted  by  Fick, 
Griitzner  and  von  Frey.  More  recently  Botazzi^  has  stated  that  a 
contracture   represents   merely   an    exaggerated    condition   of   tonus 


Ms- j«c 


Fig.  41. — Contracture  of    Muscle. 
A,  contracture;  B,  tonic  contracture;  C,  clonic  contracture. 

which  serves  as  an  "internal  support"  to  the  muscle.  It  is  a  well 
known  fact  that  tonus  varies  negatively  as  well  as  positively.  Hence, 
if  a  muscle  is  stimulated  while  maintaining  its  shortened  condition,  the 
resulting  contraction  rises  above  the  level  of  the  contracture,  but  the 
quick  shortening  observed  at  this  time  is  independent  of  the  slow 
persistent  shortening  causing  the  contracture.  It  is  believed  by 
Botazzi  that  the  former  is  made  possible  by  the  activity  of  the  aniso- 
tropic substance,  and  the  latter  by  that  of  the  isotropic  substance. 

Under  certain  conditions,  and  especially  during  irritations  of  the 
central  nervous  system,  these  prolonged  tonic  contractions  frequently 
assume  a  rhythmic  character.  They  are  then  designated  as  clonic 
contractions.  A  brief  clonus  of  certain  muscles  is  often  obtained 
in  neurasthenia  and  hysteria.  A  very  typical  one  may  be  produced 
in  certain  cases  of  organic  disease  of  the  spinal  cord  by  suddenly 
flexing  the  foot  upon  the  leg.  This  abrupt  stretching  of  the  calf 
muscles  causes  them  to  contract  rhythmically  for  some  time,  thus 
giving  rise  to  the  so-called  ankle-clonus. 

1  Jour,  of  Physiol.,  xxi,  1897,  1. 


76  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 


CHAPTER  VII 

THE  FACTORS  VARYING  THE  CHARACTER  OF  THE 
CONTRACTION 

The  Strength  of  the  Stimulus. — In  general  it  may  be  stated  that 
the  height  of  the  contraction  is  proportional  to  the  strength  of  the 
stimulus.  A  very  convenient  way  of  illustrating  this  rule  is  to  permit 
a  muscle  to  record  its  contractions  upon  a  stationary  drum  while  being 
stimulated  with  single  make  or  break  induction  shocks.  By  varying 
the  distance  between  the  secondary  and  primary  coils  of  the  induc- 
torium  the  strength  of  these  stimuli  may  be  accurately  graded.  If 
this  experiment  is  begun  with  the  coils  far  apart,  no  contractions  are 
obtained  at  first,  although  it  may  be  surmised  that  the  different 
stimuli  then  give  rise  to  certain  chemico-physical  alterations  in  the 


i 


in 
_J L 


I        2,        3        -l-         ?       6        7        8       9        to       11        li      15       ("f       fS- 


Fig.  42. — Successive  Make  and  Break  Contractions. 
The  strength  of  the  current  is  gradually  diminished  by  more  widely  separating  the 
secondary  from  the  primary  coil.     The  figures  indicate  this  separation  in  centimeters 
of  distance.     M,  threshold  of  make;  B,  threshold  of  break. 

muscle  which,  however,  are  still  too  weak  to  produce  visible  mechanical 
energy.  These  stimuli  are  said  to  be  subminimal  in  character.  If  a 
number  of  these  subminimal  stimuli  are  passed  into  the  muscle  in 
quick  succession,  they  eventually  give  rise  to  a  contraction.  This 
phenomenon  is  known  as  summation  of  subm,inimal  stimuli. 

If  the  strength  of  the  current  is  now  gradually  increased  by  bringing 
the  coils  closer  together,  a  point  will  finally  be  reached  when  the 
muscle  gives  a  just  barely  perceptible  reaction.  This  is  the  threshold 
contraction.  Moreover,  since  the  break  induction  shock  constitutes 
a  stronger  stimulus  than  the  make  shock  (page  63),  the  first  contraction 
must  appear  when  the  current  is  interrupted.  If  the  strength  of  the 
current  is  increased  still  further,  these  break  contractions  gradually 
increase  in  height  and  become  associated  with  the  first  make  contrac- 
tion. Additional  increases  in  the  strength  of  the  current  lead  to  the 
production  of  the  highest  possible  contractions,  beyond  which  point 
their  height  generally  decreases  somewhat.     Beginning  with  the  thresh- 


FACTORS  VARYING  THE  CHARACTER  OF  THE  CONTRACTION   77 

old,  tliese  contractions  arc  designated  respectively  as  minimal,  maxi- 
mal and  t^upratnaxinidl. 

The  Duration  of  the  Stimulus. — In  a  general  way  it  may  be  said 
that  the  highest  contraction  is  obtained  when  the  stimulus  is  of  long 
duration,  but  this  rule  is  applicaljle  only  to  stimuli  of  e([ual  intensity 
and  moderate  duration.  It  is  evident  that  an  undue  prolongation  of 
the  excitation  must  tend  to  produce  fatigue  and  to  lessen  the  ampli- 
tude of  the  reaction,  until  it  finally  becomes  smaller  than  the  one 
obtained  previously  with  stimuli  of  much  briefer  duration. 


0     io    20    io  "K)   SO    feo   ^0    80   <J0  joo 
Fig.  43. — Ixfluence  of  Load. 
This  muscle  has  been  successively  loaded  with  10  gram  weights. 

Influence  of  Load. — Provided  that  the  writing  lever  has  been  prop- 
erly counterpoised  so  that  weights  may  be  attached  to  it  without 
stretching  the  muscle,  the  amplitude  of  the  contractions  decreases 
gradually  with  the  increasing  load.  It  is  true,  however,  that  a  muscle 
reacts  much  better  when  moderately  weighted  than  when  no  weight  is 
attached  to  it  at  all.  In  other  words,  the  contractility  of  a  muscle 
may  be  augmented  by  subjecting  it  to  a  slight  tension. 


Vs-Jtc 

Fig.    44. — The  Coxtraction  of  Four  Different  Muscles  of  the  Turtle 

Recorded  Under  Similar  Conditions. 
1,  Palmaris;  2,  Gracilis;  3,  Omohyoid;  4,  Pectoralis  Major. 

Character  of  the  Muscle  Substance. — We  have  previously  seen 
that  the  irritabiUty,  conductivity,  and  contractility  of  muscle  tissue 
differ  not  only  in  different  animals,  but  also  in  muscles  of  the  same 
animal.  Thus,  the  striated  muscles  attached  to  the  wings  of  insects, 
contract  at  the  rate  of  300  times  in  a  second,  while  those  of  birds  may 
attain  a  frequency  of  100  in  a  second.  The  gastrocnemius  muscle  of 
the  frog  requires  0.1  sec,  the  hypoglossal  muscle  of  the  turtle  0.2-0.3 
sec,  and  those  used  in  the  retraction  of  the  head  of  this  animal  0.5  sec. 


78  PHYSIOLOGY    OF   MUSCLE    AND    NERVE 

Similar  differences  are  exhibited  by  the  red  and  pale  muscles  of  the 
rabbit,  the  soleus  (red)  contracting  in  1.0  sec.  and  the  gastrocnemius 
(pale)  in  0.2  sec.  In  winter  the  reaction-time  of  the  muscles  of  cold- 
blooded animals  is  much  prolonged.  Smooth  muscle  reacts  very  slug- 
gishly, an  ordinary  contraction  requiring  as  a  rule  from  10-20  sec.  for 
its  completion. 

It  is  evident,  therefore,  that  muscle  tissue  differs  in  its  speed  of 
reaction  and  that  this  difference  is  dependent  upon  chemico-physical 
peculiarities  of  its  substance.  We  know  that  red  muscle  is  a  more 
concentrated  tissue  than  pale  muscle  and  that  it  embraces  a  larger 
amount  of  sarcoplasmic  material.  It  seems,  therefore,  that  the  greater 
water  content  of  the  latter  exerts  a  favorable  influence  upon  its 
rapidity  of  action.  The  same  holds  true  in  the  case  of  non- 
striated  and  striated  muscle.  Inasmuch  as  the  latter  contains  more 
water  and  a  smaller  amount  of  undifferentiated  sarcoplasm,  its  speed 
of  contraction  must  be  much  greater. 


Fig.  45.— Effect  of  Chamgks  in  TisMPERATURE  on  Muscular  Contraction. 
The  temperature  was  raised  5°  each  time. 

Influence  of  Temperature. — Warmth  increases  the  power  and 
speed  of  reaction  of  this  tissue,  because  it  exerts  a  favorable  influence 
upon  the  chemical  processes  underlying  muscular  contraction.  Hence, 
a  series  of  myograms  recorded  at  gradually  rising  temperatures,  usu- 
ally shows  a  progressive  increase  in  the  height  and  corresponding  de- 
crease in  the  length  of  the  different  contractions.^  At  0°  C,  or  rather, 
a  Httle  below  this  point,  the  muscles  of  the  frog  lose  their  irritabihty 
entirely.  Consequently,  if  a  muscle  of  this  kind  is  stimulated  at  a 
degree  or  two  above  freezing,  it  gives  solely  a  very  low  and  prolonged 
contraction.  If  the  temperature  is  now  raised,  say,  three  degrees  at  a 
time,  the  individual  contractions  decrease  in  length  but  increase  in 
height.  Beginning  at  about  9°  C,  their  height  is  shghtly  decreased, 
but  again  increased  at  about  18°  C.  A  second  maximum  is  reached 
at  30°  C.  Subsequent  to  this  point  they  again  diminish  in  size  until 
1  Gad  and  Heymans,  Archiv  fur  Physiol.,  1890,  59. 


FACTORS   VARYING    THE    CHARACTER    OF   THE    CONTRACTION      79 

10  seconds,  may  not  bo  able  to  induce  fatigue.  It  is  also  essential  to 
use  maximal  wcif^lits,  because  the  effects  of  small  weights  are  jj;eiici;illy 
compensateil  for  within  a  very  shoft.  lime.  Tiie  int(!rval  whicli  should 
elapse  between  two  successive  ergograms  showing  complete  normal 
fatigue,  is  close  to  2  hours.  If  a  muscle  is  made  to  contract  before  it  has 
fully  recovered  from  a  preceding  (>xertion,  it  may  be  more  severely 
injuretl  than  if  it  had  been  forccnl  to  lift  excessive  loads  to  begin  with. 
Practically  no  two  ergograms  are  alike,  because  every  person  presents 
certain  individual  peculiarities  which  are  dependent  upon  his  physio- 
logical condition.  Thus,  pronounced  mental  or  bodily  fatigue  from 
such  causes  as  loss  of  sleep,  anemia,  lowered  nutrition,  etc.,  is  prone  to 
produce  a  more  rapid  exhaustion  of  the  muscle  than  could  possibly  be 
obtained  in  a  perfectly  robust  person.  Practice  and  training  enhance 
the  power  of  a  muscle,  and  this  end  may  also  be  attained  by  augment- 
ing the  local  or  general  circulation  by  drugs,  massage,  baths  as  well  as 
by  the  ingestion  of  certain  foods,  such  as  sugar. 


CHAPTER  VIII 


THE    CHARACTER    OF    THE    CONTRACTION    OF    SMOOTH 

MUSCLE 

The  Tonicity  of  Smooth  Muscle. — The  organs  and  structures  con- 
taining non-striated  muscle  cells  are  innervated  by  the  autonomic 
system  and  are  therefore  not  under  the  direct  control  of  the  will. 
In  fact,  they  are  in  a  way  independent  of  the  cerebro-spinal  system, 
because  their  function  continues  even  after  they  have  been  separated 
from  it.  Herein  lies  the  implication  that  they  are  well  equipped  with 
intrinsic  nervous  elements  which  are  capable  of  controlling  their  action 
even  in  the  absence  of  the  higher  centers.  If  the  bladder  or  a  segment 
of  the  stomach  or  intestine  is  excised  and  suspended  in  a  chamber 
under  proper  conditions  of  moisture  and  tempeiature,  it  may  easily 
be  observed  that  it  retains  its  tonus  and  even  executes  spontaneous 
contractions.  The  latter  may  be  of  myogenic  or  neurogenic  origin, 
although  Schultz^  claims  that  they  arise  solely  in  consequence  of  exci- 
tations of  local  nervous  elements  and  are  therefore  reflex  in  their 
character.  In  accordance  with  this  statement,  the  ordinary  condition 
of  tonus  of  non-striated  muscle  may  be  said  to  have  both  a  myogenic 
and  neurogenic  cause,  the  former  giving  rise  to  the  ordinary  elastic 
state  of  its  substance,  and  the  latter  to  periodic  excitations  which  are 
relayed  to  it  by  way  of  definite  reflex  paths.  Considered  in  this  light, 
the  spontaneous  contractions  of  smooth  muscle  are  mere  variations 
in  the  neurogenic  tonus. 

^  Archiv  ftir  Physiol.,  Suppl.,  1903,  1;  also  see:  Griitzner,  Ergebnisse  der 
Physiol.,  iii,  1904,  2. 


80  PHYSIOLOGY    OF   MUSCLE    AND    NERVE 

possible  at  this  time  to  assign  a  definite  cause  to  this  reaction.  Barium 
salts,  glycerin,  and  nicotin  produce  somewhat  similar  effects.^ 

If  a  muscle  is  placed  in  a  0.6  per  cent,  solution  of  sodium  chlorid 
or  is  frequently  moistened  with  it,  it  retains  its  functional  qualities 
for  a  long  time,  because  this  fluid  is  practically  isotonic  to  the  myo- 
plasm.  A  strong  solution  of  this  salt,  on  the  other  hand,  causes  the 
muscle  to  twitch  irregularly,  either  as  a  whole  or  along  certain  of  its 
strands  of  fibers.  The  muscle  then  exhibits  a  behavior  very  similar 
to  that  shown  by  the  fibrillating  heart.  Inasmuch  as  these  results 
are  also  obtained  with  sodium  chlorid  dissolved  in  distilled  water,  the 
ordinary  preservative  fluid  for  muscle  should  be  made  with  tap- 
water  which  contains  at  least  a  trace  of  calcium.  This  salt  neu- 
tralizes the  excitatory  action  of  the  sodium.  More  pronounced 
stimulating  effects  may  be  obtained  with  solutions  of  NazCOs,  or  with 
a  solution  containing  0.5  per  cent.  NaCl,  0.2  per  cent.  NaHP04  and  0.04 
per  cent.  Na2C03  (Biedermann).  When  mixed  in  this  proportion, 
these  salts  aie  capable  of  inducing  an  almost  rhythmic  activity  of 
skeletal  muscle.  Potassium  salts  act  as  depressants.  Thus,  even 
normal  saline  solution  when  mixed  with  a  few  drops  of  potassium,  will 
induce  fatigue  within  a  very  short  time.  Owing  to  this  fact  and  be- 
cause the  ash  of  muscle  contains  a  considerable  amount  of  potassium, 
it  has  been  thought  that  the  liberation  of  these  salts  during  muscular 
activity  is  responsible  for  the  phenomena  of  fatigue. 

Fatigue. — If  a  fresh  muscle  is  stimulated  for  some  time  with  in- 
duction shocks  of  moderate  strength,  the  successive  contractions  gradu- 
ally decrease  in  height  but  increase  in  length.  Furthermore,  if  a 
record  is  made  of  the  latent  period,  it  will  be  found  that  its  length  is 
steadily  increased,  indicating  thereby  a  very  definite  diminution  in  the 
irritability  of  the  muscle  substance.  This  observation  may  also  be 
made  upon  a  muscle  which  is  subjected  to  a  quickly  interrupted  current 
of  long  duration.  The  height  of  the  contraction  decreases  gradually 
as  the  current  is  continued.  Quite  similarly,  it  will  be  noted  that  the 
repeated  tetanization  of  a  muscle  gives  rise  to  curves  of  slowly  de- 
creasing amplitude. 

Inside  the  body,  a  muscle  cannot  be  fatigued  so  easily,  because  its 
waste  products  are  constantly  removed  by  the  blood  stream,  while  new 
substances  are  brought  to  it  to  replace  those  which  have  been  lost 
during  the  preceding  contractions.  An  excised  muscle,  on  the  other 
hand,  possesses  only  a  small  store  of  reserve  material  and  has  no 
means  of  ridding  itself  of  the  fatigue  substances.  For  this  reason, 
it  shows  these  phenomena  more  promptly  and  never  recovers  com- 
pletely from  the  stimulations.  Its  condition,  however,  may  be  ma- 
terially improved  by  perfusing  it  with  defibrinated  blood  or  normal 
saline  solution.  Contrariwise,  it  is  possible  to  hasten  its  exhaustion 
by  perfusing  it  with  a  dilute  solution  of  lactic  acid,  or  with  saline 
containing  a  considerable  amount  of  carbon  dioxid.  These  two  agents, 
1  Motinsky  and  Straub,  Arch,  fiir  exp.  Path.  u.  Pharm.,  li,  1904,  310. 


FACTORS   VARYING    THE    CHARACTER    OF    THE    CONTRACTION      81 

together  with  monopotassium  phosphate  and  certain  toxins,  are  said 
to  bo  responsible  for  the  developnient  of  f;ilifi;u('  in  muscle.  They 
are  spoken  of  collectively  as  the  fatigue  sul)stances. 

The  phenomena  of  fatigue  are  also  exhibited  by  human  muscle 
when  subjected  to  excessive  stimulation.  We  then  become  cognizant 
of  a  peculiar  strained  feeling  and  ev(Mitually  also  of  pain  which  prevents 
us  from  continuing  these  efforts.  It  appears  that  these  sensations  are 
the  direct  result  of  an  irritation  of  the  muscle-spindles  and  of  the  cor- 


iftStV 


Fig.  47. — Fatigue  of  Muscle. 
A    gastrocnemius    muscle    of    the   frog  stimulated   successively    150  times.       The 
1st,  50th,  100th,  and  150th  contractions  are  recorded. 

responding  receptors  in  the  tendons  and  joints.  Under  ordinary  con- 
ditions the  tests  upon  human  muscles  require  the  use  of  an  instrument, 
which  is  known  as  the  ergograph.  The  one  devised  by  Mosso^  consists 
of  a  support  for  the  arm  and  a  weight  which  acts  in  a  sliding  path  or 
across  a  pulley  and  is  connected  with  the  tip  of  one  of  the  fingers, 
preferably  the  index  finger  of  the  right  hand.  A  spring  ergograph, 
or  dynamograph,  has  been  devised  by  Waller.     It  consists  of  a  strong 


Fig.  48. — Fatigue  Curves  of  Frog's  Muscle.     (Waller.) 

oval  steel  spring  which  is  compressed  by  the  hand,  while  a  pointer  is 
moved  across  a  graduated  scale  to  indicate  the  degree  of  compression 
as  well  as  the  power  of  the  group  of  muscles  used  in  this  act.  In  either 
method,  the  displacement  of  the  weight  or  of  the  spring  may  be 
registered  upon  a  kymograph  by  means  of  a  writing  lever,  the  resulting 
record  being  known  as  an  ergogram. 

The  fatigue  of  human  muscle  may  be  illustrated  either  by  recording  a 
series  of  voluntary  twitches  or  a  long-continued  tetanus  of ,  say,  the  muse. 

1  Arch.  ital.  de  biologie,  xiii,  1890;  also  see:    Treves,  ibid.,  xxix,  xxx,  and  xxxi, 
1898-1900,  and  Schenck,  Pfluger's  Archiv,  Ixxxii,  1902. 


82 


PHYSIOLOGY    OF   MUSCLE    AND    NERVE 


flexor  digitorum  sublimis,   or  of  the  muse,  abductor  indicis.^     The 
former  type  of  contraction,  however,  must  be  repeated  in  rapid  suc- 


FiG.  49. — Mosso's  Ergograph. 
c,  is  the  carriage  moving  to  and  fro  on  runners  by  means  of  the  cord  d,  which  passes 
from  the  carriage  to  a  holder  attar-hed  to  the  last  two  phalanges  of  the  middle  finger 
(the  adjoining  fingers  are  held  in  place  by  clamps) ;  p,  the  writing  point  of  the  carriage, 
c,  which  makes  the  record  of  its  movements  on  the  kymograph;  u\  the  weight  to  be 
lifted.     (Howell.) 


Fig.  50. — Normal  Fatigue  Curve  of  the  Flexors  of  the  Middle  Finger  of  Right 

Hand. 
Weight  3  kilograms,  contractions  at  intervals  of  two  seconds.      (Maggiora.) 

cession,  because  even  a  load  of  as  much  as  6  kg.  Hfted  at  intervals  of 
^  Storey,  Am.  Jour,  of  Physiol.,  viii,  1903,  355. 


FACTORS    VARYING    THE    CHARACTER    OF    THE    CONTRACTION      83 

at  about  37°  C.  the  muscle  begins  to  Ios(^  its  irritability  and  to  pass, 
at  about  40°— 42°  C,  into  the  condition  of  heat  rigor.  Regarding  tht, 
cause  of  these  variations  little  can  be  said;  in  fact,  it  has  been  stated 
repeatedly  that  these  fluctuations  are  not  altogeth(;r  constant.  It 
must  be  concluded,  howev(>r,  that  muscle  tissue  requires  a  certain 
optimum  temperature  which  allows  it  to  give  reactions  of  maximal 
amplitude.  For  the  warm-blooded  animals  the  most  favorable  tem- 
perature is  37°  C,  and  for  the  cold-blooded  animals,  the  temperature 
of  the  medium  in  which  they  arc  living. 

Heat  rigor,  or  rigor  caloris,  is  a  permanent  condition,  correspond- 
ing in  a  way  to  the  coagulation  of  egg  albumin.  When  entering  this 
state,  the  muscle  gradually  shortens  and  becomes  firm  to  the  touch 
and  opaque  in  its  appearance.  These  characteristics  it  retains. 
When  placed  under  a  greater  tension  than  15-20  grams  per  gram  milli- 
meter of  substance,  it  ruptures  abruptly. 

Effect  of  Drugs  and  Chemicals. — Certain  chemicals  affect  the 
irritabiHty  and  contractility  of  muscle  in  a  very  characteristic  manner. 


'Ji'sec 

Fig.  46.— The  Effect  of  Veratrin  on  Muscular  Contraction. 

This  is  especially  true  of  veratrin.  A  few  drops  of  a  1.0  per  cent, 
solution  of  its  acetate,  injected  into  the  dorsal  lymph  sac  of  a  frog, 
generally  suffice  to  produce  its  characteristic  effect.  The  muscle  may 
also  be  immersed  in  a  solution  containing  1  part  of  the  alkaloid  to 
100,000  parts  of  a  0.7  per  cent,  solution  of  sodium  chlorid.^  By  this 
means  a  simple  twitch  of  the  gastrocnemius  may  be  made  to  last 
50-60  sec,  instead  of  the  normal  0.1  sec.  Thus,  the  peculiarities 
presented  by  a  veratrinized  muscle,  consist  in  a  surprisingly  long  period 
of  relaxation  which  usually  presents  two  summits.  It  frequently  hap- 
pens, however,  that  a  second  stimulus  sent  into  the  muscle  shortly  after 
it  has  completed  one  of  these  prolonged  contractions,  again  results  in 
a  very  rapid  twitch.  If  the  muscle  is  then  allowed  to  rest,  the  suc- 
ceeding excitation  may  again  produce  a  long  drawn-out  contraction. 
Biedermann  has  stated  that  these  pecuhar  effects  are  dependent  upon 
a  dissociation  of  the  red  and  pale  fibers  of  the  muscle.  Carvalho  and 
Weiss,  2  however,  have  observed  the  same  behavior  in  muscles  which 
are  composed  exclusively  of  either  type  of  fibers;  hence,  it  is  quite  im- 

^  Bucannan,  Jour,  of  Physiol.,  xxv,  1899,  137. 
'  Jour,  de  la  Physiol,  et  de  la  path,  gen.,  1899. 


84  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

The  Character  of  the  Contraction. — Even  the  most  casual  observa- 
tion of  the  peristaltic  wave  of  the  stomach,  intestine  or  m-eter  must 
show  that  smooth  muscle  reacts  in  a  very  sluggish  manner,  but  it  would 
be  going  too  far  to  state  that  its  irritabihty  is  less  than  that  of  striated 
tissue.  Practically  all  the  different  types  of  stimuli  are  effective;  in 
fact,  in  the  case  of  the  iris  of  the  eye  of  frogs  and  other  animals  it  is 
possible  to  produce  constrictor  reactions  even  with  light.  ^  Obviously, 
this  phenomenon  cannot  be  explained  by  saying  that  it  is  due  to  reflex 
causes,  because  the  same  results  may  be  obtained  with  small  pieces 
of  excised  iris.  It  is  also  evident  that  smooth  muscle  is  very  suscep- 
tible to  mechanical  and  thermal  stimuli,  but  rather  insensitive  to 
electrical  stimuli.  The  latter  peculiarity  necessitates  the  use  of  some- 
what stronger  induction  shocks  than  are  ordinarily  required  to  activate 
striated  muscle. 

Different  types  of  smooth  muscle  differ  in  their  speed  of  reaction, 
but,  broadly  speaking,  it  may  be  said  that  their  latent  period  is  from 


Fig.  51. — Contraction  of  Smooth  Muscle  (Cat's  Bladder.) 
L,  latent  period;  C,  period  of  contraction;   R,  period  of  relaxation;  time  in  seconds. 

100  to  500  times  as  long  as  that  of  striated  muscle.  But  inasmuch 
as  the  amplitude  of  the  reaction  of  smooth  muscle  is  directly  propor- 
tional to  the  strength  of  the  stimulus,  it  forms  no  exception  to  the 
general  law  and  gives,  therefore,  an  ascending  series  of  minimal  and 
maximal  contractions  which  increase  with  the  strength  of  the  current. 
The  chief  pecuharity  of  the  curve  of  contraction  of  smooth  muscle 
is  its  great  length.  Thus,  if  a  preparation  of  the  frog's  stomach,  the 
bladder  of  a  cat,^  or  a  segment  of  intestine  is  stimulated  with  a  current 
of  moderate  strength,  minutes  usually  elapse  before  it  again  regains  its 
normal  form.  In  the  case  of  striated  muscle,  on  the  other  hand, 
the  same  quality  of  stimulus  evokes  a  contraction  which  is  generally 
completed  in  less  than  a  second.  This  difference  is  dependent  upon 
the  fact  that  the  periods  of  contraction  and  relaxation  of  plain  muscle 
are  greatly  prolonged,  so  that  the  entire  curve  really  acquires  the  char- 
acteristics of  a  contracture  of  striped  muscle.  Inasmuch  as  its  short- 
ening is  always  accomplished  in  a  much  briefer  time  (10-15  sec.)  than 
its  relaxation  (60  sec),  it  is  claimed  by  Winkler^  that  the  strength  of 

iGuth,  Pfliiger's  Archiv,  Ixxxv,  1901,  118. 
*  C.  C.  Stewart,  Am.  Jour,  of  Physiol.,  iv,  1900,  185. 
3  Pfluger's  Archiv,  Ixxi,  1898,  386. 


THE    CHEMISTRY    OF    MUSC^LE  85 

the  stimulus  required  to  cause  it  to  contract,  must  always  be  groat 
enough  to  produce  a  contracture-like  effect.  Smooth  muscle  may  also 
be  made  to  show  the  phenomenon  of  summation  by  stimulating  it 
again  very  soon  after  it  has  entered  upon  its  period  of  relaxation. 
This  summation  may  be  repeated  until  its  maximal  degree  of  short- 
ening has  been  obtained  which,  according  to  Schultz,  is  frequently 
73  per  cent,  above  its  resting  position  or  abscissa. 

The  character  of  the  contraction  of  cardiac  muHcle  will  be  discussed 
in  a  later  chapter  dealing  with  the  dynamic  importance  of  the  heart. 
It  may  be  stated  at  this  time,  however,  that  its  contraction  is  inter- 
mediate between  those  of  striated  and  non-striated  muscle,  and  is 
most  closely  allied  to  the  simple  twitch  of  the  former.  Moreover, 
cardiac  muscle  does  not  react  intermittently,  but  possesses  an  auto- 
matic power  which  makes  it  contract  rhythmically  in  consequence  of 
the  generation  of  certain  internal  stimuli. 


CHAPTER  IX 

THE  CHEMISTRY  OF  MUSCLE 

General  Composition.^ — Inasmuch  as  the  muscle  tissue  of  an 
adult  constitutes  about  42  per  cent,  of  the  body  weight,  it  forms  a 
very  considerable  part  of  the  total  mass  of  our  body.  It  is  also  very 
important  functionally,  because  it  produces  nearly  50  per  cent,  of  the 
total  metabolism  in  persons  at  rest,  and  almost  75  per  cent,  in 
persons  undergoing  moderate  activity.  In  analyzing  muscle  tissue, 
it  must  be  taken  into  account  that  it  embraces  a  certain  amount  of 
connective  tissue  and  also  blood-vessels  and  nerves.  Its  principal 
element  is,  of  course,  the  fiber  which  is  composed  of  a  contractile 
albuminous  substance  or  sarcoplasm,  and  an  elastin-like  investment, 
or  sarcolemma.  The  former  possesses  a  semifluid  or  jelly-like  con- 
sistency and  displays  a  series  of  doubly  refracting  elements.  The 
striated  and  non-striated  types  of  mammalian  muscle  contain  from  72 
to  78  per  cent,  of  water  and  from  22  to  28  per  cent,  of  solids,  the  latter 
being  composed  largely  of  proteins. 

Proteins  of  Muscle. — The  fact  that  muscles  become  perfectly  rigid  after  death 
as  well  as  on  exposure  to  heat,  has  led  to  the  belief  that  their  albuminous  constitu- 
ents undergo  a  process  of  coagulation  similar  to  that  exhibited  by  the  blood  of  the 
warm-blooded  animals.  Thus,  Kiihne-  has  succeeded  in  isolating  from  them  a 
liquid  by  first  freezing  them  and  then  subjecting  them  to  a  high  pressure.  This 
so-called  muscle-plasma  clots  almost  immediately  when  slightly  warmed.  The 
remaining  portion  of  the  muscle  substance  forms  the  so-called  stroma.  Under 
ordinary  conditions  it  suffices  to  divide  the  muscle  into  small  pieces  and  to  subject 

'v.  Fiirth,  Oppenheimer's  Handb.  der  Biochemie,  Jena,  1910. 
^  Unters.  liber  das  Protoplasma,  Leipzig,  1864. 


86  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

them  to  a  pressure  of  from  250-300  atmospheres.  About  60  per  cent,  of  the  weight 
of  the  muscle  is  then  obtained  as  plasma. 

The  Proteins  of  the  Plasma. — Halliburton,  i  has  shown  that  muscle-plasma 
contains  two  coagulable  proteins,  namely  mj-osin  and  myogen  which  upon  coagu- 
lation are  transformed  into  myosinfibrin  and  myogenfibrin.  But  this  transfer 
does  not  seem  to  be  a  direct  one,  because,  in  the  case  of  myogen,  v.  Fiirth  has  found 
an  intermediary  product  which  he  has  called  soluble  myogenfibrin.  This  author 
also  calls  attention  to  the  fact  that  the  coagulation  of  muscle-plasma  is  not  strictly 
comparable  to  the  coagulation  of  blood,  as  has  been  held  by  Kuhne  and  Halli- 
burton, because  the  clot  is  fioccular  and  forms  as  a  rule  very  slowly.  Furthermore, 
while  fresh  muscle-plasma  is  neutral  or  sUghtly  alkaline  in  reaction,  it  becomes 
distinctly  acid  after  coagulation  has  set  in.  This  acidity  is  due  to  the  formation 
of  sarcolactic  acid.  The  serum  formed  in  the  course  of  this  process,  contains  the 
soluble  constituents  of  muscle. 

The  Proteins  of  the  Stroma. — The  residue  left  over  after  the  plasma  has  been 
squeezed  out,  consists  chiefly  of  connective  tissue,  sarcolemma  and  nuclei.  By 
preventing  as  much  as  possible  the  occurrence  of  rigor  in  the  excised  muscles,  SaxP 
has  found  that  only  a  small  portion  of  their  total  mass  consists  of  stroma.  He  also 
states  that  the  plasma  proteins  in  skeletal  muscle  amount  to  seven-eighths  of  the 
total  protein  content,  while  their  relationship  in  cardiac  muscle'  is  as  }yi  :  %  and 
in  smooth  muscle  as  3-^  :^i.  The  stroma  contains  phosphorus  which  is  held 
in  the  nucleoprotein.  It  also  embraces  phospholipins  in  combination  with  the 
proteins. 

Lipins  of  Muscle. — The  fat  of  muscle  is  contained  chiefly  in  the  connective 
tissue  between  its  different  bundles,  but  a  certain  amount  of  it  is  also  held  in  the 
cells  themselves.  On  analysis  the  former  in  all  probability  gives  rise  to  neutral 
fat,  while  the  latter  yields  cholesterol  and  phospholipins.  The  proportion  of  these 
bodies  differs  greatly  in  different  types  of  muscle  tissue.  In  skeletal  muscle,  they 
may  amount  to  as  much  as  30  per  cent.,  and  in  cardiac  muscle  to  as  much  as  60 
or  70  per  cent,  of  the  total  lipins.*  Cardiac  tissue  is  characterized  by  a  large  per- 
centage of  cuorin  which  is  a  monoamidodiphosphatide. 

Carbohydrates  of  Muscle.^ — The  presence  of  glycogen  in  muscle  tissue  was 
recognized  soon  after  the  discovery  of  this  substance  by  Claude  Bernard.  It  may 
be  present  in  considerable  amounts,  namely  1.0  per  cent,  in  the  muscles  of  the  cat, 
0.4-0.7  per  cent,  in  those  of  man,  and  as  much  as  3.7  per  cent,  in  those  of  the  dog. 
It  seems  to  be  derived  from  the  sugar  of  the  blood,  mu.scle  tissue  possessing  the 
power  of  converting  the  monosaccharide  dextrose  by  dehydration  and  condensa- 
tion into  the  polysaccharide  glycogen.  The  following  formula  may  serve  to  illus- 
trate this  reaction : 

N(C6Hi206)  -  NCHsO)  =  (C6Hio06)N 

Glycogen  is  stored  in  the  muscle  tissue  and  forms  an  important  nutritive  material. 
For  this  reason,  it  must  be  a  constant  constituent  of  all  well-nourished  resting 
muscles. 

Inorganic  Constituents. — Muscle  tissue  contains  a  number  of  salts  such  as  the 
chlorides,  sulphates  and  phosphates  of  sodium,  potassium,  calcium,  magnesium 
and  iron,  but  its  chief  characteristic  is  its  large  content  in  potassium  and  phos- 
phoric acid.^  The  total  amount  of  phosphorus  is  0.2  per  cent.,  it  being  present 
chiefly  in  an  inorganic  form.  Ox  muscle,  for  example,  contains  81  per  cent,  of 
inorganic  and  19  per  cent,  of  organic  phosphorus,  while  heart  muscle  embraces 

1  Jour,  of  Physiol.,  viii,  1888,  133. 

^  Hofmeister's  Beitrage,  ix,  1906,  1. 

^  Lederer  and  Stotte,  Biochem.  Zeitschr.,  xxxv,  1910,  108. 

*  Erlandson,  Zeitschr.  flir  phys.  Chemie,  li,  1907,  71. 

5  V.  Fiirth,  Ergebn.  der  Physiol,  Bioch.,  ii,  1903,  580. 

«  Urano,  Zeitschr.  fur  Biol.,  1,  1907,  212. 


THE    CHEMISTRY    OF   MUSCLE  87 

40  per  cent,  of  the  former  and  (10  per  cent,  of  the  latter.  By  far  the  greatest 
amount  of  organic  phosphoru.s  is  present  in  the  form  of  phosphatide. 

Lactic  Acid. — Most  generally  muscle  tis-sue  also  contains  a  certain  amount  of 
ethidene  lactic  acid  or  sarcolactic  acid,  CHriCHOIICOOII.  This  acid  is  a  product 
of  tissue  metabolism.  It  is  dextrorotary,  while  that  contained  in  sour  milk,  is  in- 
active to  polarized  light  and  finds  its  origin  in  bacterial  fermentations.  In  normal 
resting  muscle  it  is  iliflicult  to  detect  it,  because  it  is  oxidized  as  rapidly  as  it  is 
formed,  but  its  removal  may  be  greatly  interfered  with  by  restricting  the  entrance 
of  oxygen.     The  amount  of  this  acid  is  greatly  augmented  during  muscular  activity. 

Extractives. — If  muscle  tissue  is  extracted  with  boiling  water,  a  number  of  sub- 
stances are  obtained  which  are  of  especial  interest,  because  they  represent  in  all 
probability  the  products  of  the  metabolism  of  muscle.  Chief  among  these  are 
those  of  nitrogenous  origin,  because  they  give  rise  to  some  of  the  substances  ex- 
creted in  urine.  As  a  rule,  fresh  muscle  yields  about  2  per  cent,  of  its  weight  in 
extractives  of  which  0.7  per  cent,  is  of  organic  and  L3  per  cent,  of  inorganic  origin. 
The  one  present  in  largest  amounts  is  creatin,  C4H9N3O2,  which  equals  0.1  to  0.4 
per  cent,  of  the  weight  of  the  mammalian  muscle.  Creatinin,  C4H7N3O,  is  present 
in  much  smaller  amounts,  but  constitutes  0.3  per  cent,  of  the  weight  of  the  muscles 
of  fish.  No  definite  conclusions  have  been  reached  as  yet  regarding  the  origin  of 
these  bodies  and  even  the  statement  of  Liebig  and  Ranke,'  that  creatin  is  a  fatigue 
substance  and  increases  with  muscular  .activity,  has  not  been  substantiated  by 
the  more  recent  and  more  exact  quantitative  determinations  of  these  substances.'^ 
Carnosin,-^  CgHi4N405,  is  a  basic  extractive  and  is  said  to  be  derived  from  histidin, 
because  on  hydrolysis  it  yields  histidin  and  /3-alanin.  It  is  present  in  about  the 
same  proportion  as  creatin.     Other  bodies  are  carnitin,  novain  and  taurin. 

The  ■purins  of  muscle  are  relatively  scanty  in  amount,  because  by  far  the  great- 
est part  of  the  muscle  cell  is  composed  of  cytoplasm.  They  are  represented  by 
such  bodies  as  uric  acid  (C0H4N4O3),  xanthin  (C5H4N4O2),  hypoxanthin  (C6H4N4O), 
guanin  (C5H5N5O),  adenin  (C5H5N5)  and  carnin  (C7H8N4O3).  Urea  is  present  in 
very  small  amounts  in  the  muscles  of  mammals  (0.04  to  0.08  per  cent.),  but  in 
much  larger  quantities  in  the  muscles  of  certain  fish  (1  to  2  per  cent.). 

Pigments  and  Enzymes. — The  red  color  of  muscle  is  said  to  be  due  to  a  pigment 
which  is  known  as  mj-ohematin  or  myochrome.  Inasmuch  as  this  body  presents 
several  of  the  characteristics  of  hemoglobin,  it  is  commonly  said  to  be  identical 
with  it.  Its  chief  function  is  respiratory,  because  it  furnishes  the  muscle  with 
oxygen  which  it  holds  in  loose  combination. 

The  substances  furnished  to  the  muscles  by  the  blood,  are  made  available  for 
their  metabolism  by  hydrolysis,  oxidation,  reduction  and  synthesis.  It  is  believed, 
therefore,  that  muscle  tissue  is  in  possession  of  certain  enzymes  which  are  capable 
of  instigating  these  processes.  Their  function  is  proteolytic,  lipolytic  and  amylo- 
lytic.  They  also  act  as  oxidases  or  peroxidases,  reductases,  deaminases,  etc.  The 
products  of  muscular  metabolism  frequently  exert  a  certain  influence  upon  the 
function  of  other  structures.  Thus,  lactic  acid  and  carbon  dioxid  serve  as  stimu- 
lants to  the  respiratory  center,  while  the  accumulation  of  these  and  other  bodies 
in  consequence  of  disturbances  in  their  excretion,  may  give  rise  to  toxic  symptoms. 

The  Chemical  Changes  in  Contracting  Muscle. — The  metabolic 
alterations  in  the  contracting  muscle  are  characterized  by  a  constancy 
of  the  catabolism  of  the  proteins  and  an  increase  in  the  catabolism  of 
the  carbohydrates,  together  with  a  production  of  lactic  acid  and  carbon 
dioxid.  This  is  clearly  shown  by  the  fact  that  muscular  work  does  not 
augment  the  nitrogen  output  of  the  muscle  nor  of  the  body,  but  is 

1  Tetanus,  eine  physiol.  Studie,  Leipzig,  186.5. 

2]Grindley  and  Woods,  Jour.  Biol.  Chem.,  ii,  1906,  309;  Urano,  Hofmeister's 
Beitrage,  ix,  1906,  104,  and  Mej^ers  and  Fine,  Jour.  Biol.  Chem.,  xv,  1913,  283. 
'  Gulewitch  and  Amiradzibi,  Zeitschr.  phys.  Chem.,  xxx,  1900,  565. 


88  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

followed  by  (a)  a  greater  production  of  carbon  dioxid  and  a  greater  con- 
sumption of  oxygen,  (6)  a  formation  of  lactic  acid,  and  (c)  a  gradual 
disappearance  of  the  glycogen.  Hence,  as  the  contraction  of  a  muscle 
is  made  possible  by  chemical  alterations  in  the  myoplasm,  it  must  be 
evident  that  this  energy  is  chiefly  derived  from  the  carbohydrates. 
The  statement  that  this  foodstuff  is  the  most  available  source  of 
muscular  energy,  is  substantiated  further  by  the  fact  that  muscular 
exercise  immediately  raises  the  respiratory  quotient. 

The  production  of  carbon  dioxid  by  the  active  muscles  is  clearly  proved  by  the 
fact  that  the  expired  air  contains  a  larger  amount  of  carbon  dioxid  than  the 
inspired.  Obviously,  this  gas  is  transferred  from  the  tissues  to  the  blood  and 
is  subsequently  gotten  rid  of  through  the  respiratory  channel.  It  has  also  been 
shown  that  an  excised  muscle  evolves  a  much  larger  quantity  of  carbon  dioxid 
when  tetanized  than  when  allowed  to  rest.^  This  increased  production  of  carbon 
dioxid  is  associated  with  an  increased  intake  of  oxygen,  but  the  respirator}^  quo- 

CO 
tient,  ——^'  increases,  because  the  output  of  carbon  dioxid  exceeds  the  absorption 

O2 
of  oxygen.  Moreover,  this  evolution  of  carbon  dioxid  ceases  if  no  oxygen  is  al- 
lowed to  enter  the  body.  In  explanation  of  these  phenomena  it  has  been  stated 
that  this  gas  does  not  constitute  a  primary  product,  but  arises  secondarily  in  con- 
sequence of  the  oxidation  of  the  products  of  muscular  metabolism.  ^  Thus,  it  has 
been  assumed  that  the  chemical  processes  in  muscle  result  first  of  all  in  a  decom- 
position of  the  complex  nutritive  material  into  intermediary  substances,  such  as 
lactic  acid,  which  are  then  reduced  in  the  presence  of  an  adequate  supply  of  oxygen. 

This  explanation  finds  substantiation  in  the  fact  that  frog's  muscle,  when  sus- 
pended in  an  atmosphere  of  nitrogen,  soon  ceases  to  respond  to  stimulation.  If  it 
is  then  subjected  to  an  analysis,  it  will  be  found  to  contain  0.2  per  cent,  of  lactic 
acid,  but  only  traces  of  carbon  dioxid.  The  latter,  in  all  probability,  have  been 
liberated  in  consequence  of  the  change  of  the  muscle  medium  from  faintly  alkaline 
to  acid.  Conversely,  if  a  muscle  is  first  fatigued  in  an  atmosphere  of  nitrogen, 
and  is  then  transferred  into  a  medium  of  pure  ox^-gen,  it  soon  recovers  its  irritability 
and  may  be  stimulated  for  a  long  time  before  it  again  exhibits  indications  of 
fatigue.  On  subsequent  analysis,  it  will  be  found  to  contain  practically  the  same 
amount  of  lactic  acid  as  resting  muscle,  but  much  larger  quantities  of  carbon 
dioxid.  A  contracting  muscle,  therefore,  liberates  carbon  dioxid  in  amounts 
which  are  almost  directly  proportional  to  the  quantity  of  oxygen  available  for  the 
reduction  of  the  lactic  acid. 

The  Formation  of  Lactic  Acid. — Resting  muscle  exhibits  a  neutral  or  feebly 
alkaline  reaction,  while  active  muscle  is  distinctly  acid.^  This  general  statement, 
as  we  have  just  seen,  holds  true  only  if  inconsiderable  amounts  of  oxygen  are 
available,  because  a  copious  supply  of  this  gas  reduces  the  sarcolactic  acid  still 
further,  while  a  scarcity  of  it  causes  the  acid  to  accumulate.  But,  since  mechanical 
manipulation  and  thermal  and  chemical  irritations  are  very  prone  to  increase  the 
production  of  this  acid,  it  is  difficult  to  obtain  an  excised  muscle  with  a  perfectly 
neutral  reaction.*  In  most  cases  it  will  show  an  acidity  equalling  0.02  per  cent., 
expressed  as  zinc  lactate.  This  may  be  considerably  increased  (0.2  per  cent.)  by 
causing  the  muscle  to  undergo  a  few  contractions.  Blue  litmus  paper  will  then  be 
reddened  and  brown  turmeric  paper  turned  yellow. 

The  production  of  lactic  acid  during  muscular  activity  may  be  proved  by  inject- 
ing a  solution  of  acid  fuchsin  into  the  dorsal  lymph  sac  of  a  frog,  whence  it  will  be 

^  Hermann,  Unters.  iiber  d.  Stoffwechsel  d.  Muskeln.,  Berlin,  1867. 

2  Fletcher,  Jour,  of  Physiol.,  xxviii,  1902,  474. 

'  Proved  by  DuBois-Reymond,  in  1859. 

*  Fletcher  and  Hopkins,  Jour,  of  Physiol.,  xxxv,  1907,  247;  and  xliii,  1911,  12. 


THE    CHEMISTRY    OF    MUSCLE  89 

absorbed  and  distributed  to  the  different  tissues  throup;li  the  circulation,  but  as  the 
different  media  of  tlie  body  are  normally  neutral  or  faintly  alkaline,  no  change  in 
color  will  result.  If  one  of  the  posterior  extremities  is  lunv  tetanized  by  stimulating 
its  sciatic  nerve,  the  muscles  so  activated  gradually  assume  a  reddish  hue.  This 
change  appears  more  quickly,  if  the  corresponding  femoral  artery  is  ligated  after 
the  injection  of  the  fuchsin,  because  lessening  the  oxygen  supply  greatly  favors 
the  accumulation  of  lactic  acid. 

The  origin  of  the  lactic  acid  in  muscle  has  been  the  subject  of  much  contro- 
versical  discussion.  Some  investigators,  indeed,  have  sought  to  displace  the  old 
view  of  Liebig  which  holds  that  the  acidity  of  muscle  is  due  to  the  formation  of 
lactic  acid,  by  the  theory  that  it  is  caused  by  the  mono-phosphate  of  potassium. ' 
Again,  it  has  been  assumed  that  the  free  lactic  acid  acts  on  the  potassium  biphos- 
phate  normally  present  in  muscle  and  forms  potassium  lactate  by  the  reduction  of 
the  neutral  into  acid  phosphate.  It  is  also  believed  that  lactic  acid  arises  in  the 
course  of  the  disintegration  of  glycogen,  but  this  view  seems  untenable  because  it 
has  been  shown  that  the  glycogen  content  of  muscle  in  death-rigor  remains  prac- 
tically the  same,  in  spite  of  the  fact  that  its  content  in  lactic  acid  is  very  high, 
namely  0.5  per  cent.  In  addition,  it  has  been  proved  that  muscles  which  have  been 
deprived  of  their  glycogen  by  fasting,  yield  as  much  lactic  acid  as  normal  muscles. 
Hill,*  moreover,  claims  that  the  precursor  of  lactic  acid  is  a  substance  which 
possesses  a  heat  value  at  least  70  per  cent,  greater  than  that  of  this  acid.  But 
the  heat  liberated  by  dextrose,  is  only  slightly  greater  (3  per  cent.)  than  that  of 
lactic  acid,  and  furthermore,  an  excised  muscle  frequently  yields  a  quantity  of  acid 
which  is  considerably  above  that  actually  to  be  derived  from  the  glycogen  normally 
present  in  muscle.  These  results  clearly  demonstrate  that  glycogen  cannot  be  the 
mother-substance  of  this  acid.  The  only  alternative,  therefore,  is  that  it  is  a  de- 
rivative of  the  proteins.  More  recently,  it  has  been  asserted  that  muscle  tissue 
contains  a  carbohydrate-phosphoric  acid  group  which  yields  lactic  and  phosphoric 
acids  in  about  equimolecular  amounts.  It  is  believed  that  the  sugar  of  muscle  is 
synthetized  with  phosphoric  acid  and  other  constituents  into  the  aforesaid  complex 
compound.  On  breaking  down,  the  carbohydrate  group  of  this  body  gives  rise 
to  lactic  acid. 

The  Disappearance  of  Glycogen. — Weiss^  has  shown  that  frog's  muscle  loses 
from  24  to  50  per  cent,  of  its  glycogen  on  tetanization.  This  observation  has  been 
confirmed  repeatedly  by  other  investigators  so  that  it  may  now  be  considered  as 
definitely  proven  that  this  constituent  of  muscle  diminishes  during  activity.  A 
normal  resting  muscle,  on  the  other  hand,  increases  its  store  in  glycogen  and  much 
more  rapidly,  if  its  motor  nerve  is  cut  to  prevent  contraction.  In  a  similar  way, 
it  may  be  proved  that  general  muscular  exercise  reduces  not  only  the  glycogen  store 
of  the  muscles,  but  also  that  of  the  liver.  This  consumption  of  glycogen  may  be 
rendered  even  more  striking  by  temporarily  discontinuing  the  intake  of  food. 
Cardiac  muscle,  in  particular,  possesses  very  marked  storing  qualities,  and  retains 
its  glycogen  even  more  tenaciously  than  skeletal  muscle.* 

The  liberation  of  heat  and  electrical  changes  concomitant  with  muscular  con- 
traction, will  be  discussed  in  a  later  chapter.  Suffice  it  to  say  at  this  time  that  the 
muscles  constitute  the  chief  heat  producing  tissue  of  our  body  and  that  their 
activity  is  associated  with  clearly  recognizable  electrical  variations. 

The  Chemistry  of  the  Fatigue  of  Muscle. — We  have  previously 
seen  that  the  continued  or  excessive  stimulation  of  muscle  eventually 
causes  it  to  become  functionally  useless.  It  loses  its  irritability  and 
contractility  so  that  even  the  strongest  stimulus  is  no  longer  able  to 

iDreser,  Zentralbl.  fiir  Physiol.,  i,  1887,  195. 
2  Jour,  of  Physiol.,  xlvi,  1913,  28. 
2  Sitzungsb.  der  Wiener  Akad.,  Ixiv,  1871. 
*  Aldehoff,  Zeitschr.  fiir  Biol.,  xxv,  1889,  137. 


90  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

activate  it,  and  naturally,  an  excised  muscle  is  more  susceptible  to 
fatigue  than  a  normal  one,  because  it  is  quite  unable  to  obtain  new- 
material  and  to  discharge  the  products  of  its  metabolism.  Likewise, 
it  may  be  inferred  that  a  normal  muscle  is  able  to  regain  its  functional 
qualities  within  a  relatively  short  time,  while  an  excised  muscle  is  not. 
This  exhaustion,  therefore,  is  referable  to  two  causes,  namely  an 
insufficient  supply  of  nutrient  material,  inclusive  of  oxygen,  and  an 
accumulation  of  depressing  waste  products.  The  fact  that  substances 
of  this  kind  are  actually  formed,  needs  no  further  substantiation, 
because  Ranke^  has  shown  that  the  irritability  of  a  fatigued  muscle 
may  be  restored  by  perfusing  it  with  an  ordinary  non-nutritive  solu- 
tion, such  as  sodium  chlorid.  In  addition,  this  investigator  has 
proved  that  the  injection  of  extracts  of  the  fatigued  muscles  of  one 
frog  into  the  circulation  of  another  gives  rise  to  a  typical  depression 
in  the  second  animal.  Inasmuch  as  these  results  can  also  be  obtained 
with  solutions  of  lactic  acid  and  creatin,  he  gave  to  these  agents 
the  name  of  "fatigue  substances,"  and  later  on  included  under  this 
term  also  carbon  dioxid  and  acid  potassium  phosphate.  (KH2PO4). 
More  recently  Mosso^  has  extended  these  experiments  to  warm-blooded 
animals  and  has  shown  that  the  transfusion  of  the  blood  of  a  fatigued 
dog  into  the  circulatory  channels  of  a  second  perfectly  normal  dog 
produces  in  the  latter  most  decided  symptoms  of  fatigue. 

Weichardt^  has  attempted  to  add  to  the  three  fatigue  substances 
carbon  dioxid,  lactic  acid  and  monopotassium  phosphate,  also  a 
certain  specific  muscle  toxin  which  he  calls  kenotoxin.  When  isolated 
from  the  other  substances,  this  toxin,  when  injected  into  other  animals, 
is  capable  of  producing  the  phenomena  of  fatigue.  He  also  claims  to 
have  obtained,  by  bacteriological  methods,  an  antitoxin  which  serves 
to  counteract  the  effects  of  this  toxin  and  to  retain  the  muscle  in  a 
reactive  condition.  These  tests  have  more  recently  been  repeated  by 
Lee  and  Aranowich,^  but  no  evidence  has  been  found  to  substantiate 
the  formation  of  an  actual  muscle  toxin. 

It  has  also  been  shown  by  Lee^  that  small  quantities  of  any  of  the 
three  fatigue  substances  previously  mentioned,  cause  a  temporary  aug- 
mentation in  the  activity  of  the  muscle,  as  is  evinced  by  an  increase 
in  its  irritability  and  working  power.  Thus,  if  a  muscle  is  succes- 
sively stimulated  at  intervals  of,  say,  one  second  and  its  contractions 
are  registered  upon  a  slowly  revolving  drum,  the  injection  of  a  small 
amount  of  any  one  of  these  agents  temporarily  increases  the  height 
of  these  contractions.  In  this  manner  the  curve  may  be  made  to  show 
periodic  augmentations.  This  phenomenon  is  known  as  the  "  Treppe. " 
In  this  connection  it  might  also  be  mentioned  that  these  staircase- 

1  Tetanus,  Leipzig,  1865. 

2  Arch,  de  biolog.  ital.,  xiii,  1890. 

3  Miinchener  med.  Wochenschr.,  li,  1904,  12;  lii,  1905,  1234;  and  liii,  1906,  1701. 
*  Proc.  Exp.  Soc.  of  Biology  and  Medicine,  1917. 

"  Am.  Jour,  of  Physiol,  xx,  1908,  170. 


THE    CHEMISTRY    OF    MUSCLE  91 

liko  increases  arc  frequently  observed  at  the  beginning  of  a  series  of 
contractions  of  either  striated,  non-striated  or  cardiac  muscle  when 
stimulated  with  induction  shocks  of  constant  strength.  According 
to  Lee,  this  initial  "Trei)pe"  is  due  to  a  sudden  increase  in  the 
irrita])ilit3'-  of  the  nuiscle,  following  the  early  production  and  accumula- 
tion of  small  quantities  of  the  fatigue  substances.  It  may  be  accepted 
as  proven  that  the  seat  of  this  excitation  is  the  myoplasm  and  not  the 
neuroplasm,  because  these  increases  also  develop  in  curarized  muscles 
and  in  muscles  which  have  suff(n-ed  a  degeneration  of  their  nervous 
elements. 

The  Chemistry  of  Rigor  Mortis. — The  condition  of  death  rigor  is 
characterized  by  a  rigidity  of  the  musculature  which  makes  its  appear- 
ance ver^'  shortly  after  the  general  functions  of  the  body  have  ceased. 
It  manifests  itself  by  a  loss  of  the  irritability  and  contractility  of  the 
myoplasm.  The  muscle  becomes  opaque,  stiff,  and  firm  to  the  touch 
and,  unless  its  tendency  to  shorten  is  opposed  by  a  slight  counterforce, 
is  prone  to  assume  a  state  of  very  slight  contraction. 

Under  ordinary  conditions,  rigor  mortis  affects  the  different  muscles 
in  a  definite  sequence  from  above  downward,  beginning  with  those  of 
the  jaws  and  neck  and  finally  involving  those  of  the  trunk,  arms  and 
legs.  It  is  also  noted  that  these  muscles  are  affected  gradually,  i.e., 
fiber  after  fiber  and  not  simultaneously  throughout  their  substance. 
The  degree  of  their  shortening  is  determined  by  the  weight  of  the  part 
moved  by  them  and  the  force  opposing  this  tendency.  Thus,  the 
simultaneous  stiffening  of  the  flexors  and  extensors  finally  gives  rise 
to  a  fixed  position  of  the  extremities  so  that  the  joints  become  im- 
movable, but  inasmuch  as  these  muscles  are  antagonistically  placed, 
practically  no  shortening  results.  This  fact  that  the  muscle  in  rigor 
retains  its  normal  form  almost  completely,  may  be  more  plastically 
portrayed  by  cutting  the  tendons  of  either  the  flexors  or  extensors  of 
the  foot  at  death.  It  will  then  be  found  that  the  subsequent  rigor 
of  the  opposing  muscles  does  not  materially  change  the  position  of  the 
foot. 

The  time  required  for  the  development  of  rigor  mortis  is  very 
variable.  Most  generally  it  makes  its  appearance  in  from  1  to  5  hours, 
but  in  some  cases  it  may  begin  as  early  as  10  minutes  after  death.  A 
delay  of  from  20  to  24  hours  is  not  unusual.  Under  certain  conditions 
it  may  develop  almost  instantaneously,  giving  rise  to  the  so-called 
cataleptic  rigor.  Thus,  it  is  narrated  that  soldiers  have  been  found 
in  rigor  with  the  gun  at  their  shoulders  and  with  one  eye  open  and  the 
other  closed  as  in  the  act  of  taking  aim.  In  all  these  and  similar  cases, 
the  central  nervous  system  was  found  to  have  been  seriously  lacerated. 
The  duration  of  rigor  mortis  is  also  very  uncertain,  because  it  may 
last  anywhere  from  a  few  hours  to  a  few  days,  or  even  a  week.  A 
quick  onset,  however,  usually  suggests  a  short  duration.  Forced 
movement  of  the  parts  frequentl}^  tends  to  bring  on  relaxation. 

The  factors  which  may  be  held  responsible  for  this  variation  in  the 


92  PHYSIOLOGY  OF  MUSCLE  AND  NERVE 

character  of  rigor  mortis  are  several.  First  of  all  we  might  mention  the 
condition  of  the  muscles  at  the  time  of  death.  Thus,  it  is  a  matter  of 
common  observation  that  muscles  which  have  been  enfeebled  by  dis- 
ease show  a  rapid  onset  and  dissolution,  while  strong  and  vigorous 
muscles  are  affected  rather  slowly.  Cold  delays  and  warmth  hastens 
its  onset.  The  same  is  true  of  muscular  fatigue  and  certain  diseases 
of  the  spinal  cord  and  brain.  Extensive  lesions  of  these  parts  greatly 
favor  its  development.  Young  individuals,  and  especially  infants, 
are  affected  more  rapidly  than  adults,  and  red  muscles  more  slowly  than 
pale  muscles. 

In  analogy  with  muscular  contraction  it  is  believed  that  rigor 
mortis  is  caused  by  a  coagulation  of  the  protein  material.  It  is  held 
that  the  myosin  and  myogen  are  temporarily  converted  into  their 
insoluble  forms,  ^  myosinfibrin  and  myogenfibrin,  this  change  being 
associated  with  an  increase  in  the  acidity  of  the  muscle.  Inasmuch 
as  the  latter  is  dependent  upon  the  production  of  lactic  acid,  it  has 
been  assumed  that  this  acid  is  the  actual  cause  of  this  coagulation, 
or  is  at  least  very  closely  concerned  with  it.  This  inference  is  entirely 
justified,  because  lactic  acid  is  not  copiously  produced  in  the  presence 
of  an  abundant  supply  of  oxygen.  Rigor  mortis  then  fails  to  develop. 
A  deficiency  in  oxygen,  on  the  other  hand,  favors  the  accumulation  of 
lactic  acid  and  hence,  also  the  occurrence  of  this  condition.  In  accord- 
ance with  this  conception,  the  dissolution  is  said  to  be  dependent  upon 
the  reestablishment  of  the  neutral  reaction  of  the  medium  or  upon 
intracellular  autolyses  due  to  ferments.^  It  has  been  proved,  however, 
that  bacteria  are  not  the  primarj^  cause  of  the  dissolution,  because  the 
rigor  also  disappears  when  their  growth  is  prevented.^  In  analogy 
with  the  coagulation  of  the  blood,  the  attempt  has  also  been  made  by 
Danilewsky*  and  others  to  bring  the  development  of  rigor  mortis  into 
relation  with  the  calcium  content  of  the  muscle  plasma.  We  have  prev- 
ioush^  seen  that  this  relationship  is  only  a  general  one;  moreover,  it 
has  been  shown  that  calcium-free  solutions  of  myogen  are  not  exempt 
from  coagulation.^ 

In  the  third  place,  a  muscle  in  rigor  mortis  gives  rise  to  a  consider- 
able amount  of  carbon  dioxid  which  may  have  its  source  either  in  an 
increased  general  catabolism  or  in  those  oxidations  which  are  primarily 
concerned  with  the  reduction  of  lactic  acid.  In  accordance  with  the 
experiments  of  Fletcher  and  Brown,  ^  this  point  has  been  decided  in 
favor  of  the  latter  view,  the  increase  in  carbon  dioxid  being  the  indirect 
result  of  the  formation  and  oxidation  of  the  lactic  acid.  Some  ob- 
servers also  claim  that  the  glycogen  content  of  muscle  is  diminished 
during  rigor  mortis. 

1  Saxl,  Hofmeister's  Beitrage,  ix,  1906,  L 

i*  Vogel,  Deutsch.  Arch,  fur  klin.  Med.,  1902,  292. 

sBierfreund.  Pfliiger's  Archiv,  xliii,  1888,  195;  and  Karpa,  ibid.,  cxii,  1906,  199. 

*  Zeitschr.  phys.  Chemie,  vi,  1882,  158. 

'  V.  Furth,  Hofmeister's  Beitrage,  iii,  1903,  453. 

»  Jour,  of  Physiol.,  xlviii,  1914,  177. 


THE    PRODUCTION    OF    ENERGY    IN    MUSCLE  93 

The  Chemistry  of  Rigor  Caloris. — It  has  previously  been  shown 
that  the  continued  apphcation  of  heat  causes  the  muscle  to  lose  its 
irritability  and  to  become  functionally  useless.  In  this  condition  of 
rigor  caloris  the  muscle  presents  an  opaque  appearance,  a  firm  con- 
sistency and  a  change  in  its  form,  approaching  its  state  of  maximal 
shortening.  The  skeletal  muscles  of  the  frog  enter  this  condition  at  40° 
or  41°  C,  while  those  of  warm-blooded  animals  require  a  temperature 
of  about  47°  C.  This  difference  in  their  behavior  may  be  ascribed  to 
the  fact  that  the  muscles  of  amphibia  contain  preformed  soluble 
myogen  fihrin  which  coagulates  at  40°  C,  while  those  of  mammals  con- 
tain solul)le  myosin  which  coagulates  at  47°  to  50°  C.  While  rigor 
caloris  may  be  said  to  be  dependent  upon  a  conversion  of  the  proteins^ 
into  their  insoluble  forms,  a  muscle  entering  this  condition  also  liber- 
ates carbon  dioxid  and  heat,  and  acquires  a  larger  store  of  lactic 
acid.  Fletcher  claims  that  this  carbon  dioxid  is  preexisting  and  is  set 
free  at  40°  C.  from  carbonates  and  similar  bodies  through  the  inter- 
vention of  the  lactic  acid.  At  higher  temperatures  (75°  C.)  it  is  given 
off  by  the  colloids  and  amino-acids. 

Muscles  may  also  be  thrown  into  a  state  of  rigor  by  means  of  a 
number  of  chemical  substances.  Water-rigor,  for  example,  results  in 
consequence  of  their  immersion  in  distilled  water,  while  coagulation- 
rigor  is  the  outcome  of  the  coagulation  of  their  protein  material 
by  such  agents  as  alcohol  and  chloroform.-  The  same  result  may  be 
obtained  with  dilute  acids,  veratrin,  caffein,  quinine  and  different  tox- 
ins.^ While  it  is  often  difficult  to  differentiate  between  these  different 
types  of  rigor,  heat  rigor  may  easily  be  distinguished  from  death  rigor, 
because  the  former  is  a  permanent  and  the  latter  a  temporary  condi- 
tion. Furthermore,  a  muscle  in  rigor  caloris  shows  a  more  decided 
opacity,  and  possesses  a  more  soHd  consistency  than  a  muscle  in  rigor 
mortis.  The  latter  is  rather  unevenly  turbid  and  its  color  may  be 
considerably  lightened  by  a  0.2  per  cent,  solution  of  sulphuric  acid. 


CHAPTER  X 
THE  PRODUCTION  OF  ENERGY  IN  MUSCLE 

Forms  of  Energy  Liberated. — Life  manifests  itself  by  incessant 
changes  and  every  manifestation  of  it  necessitates  the  liberation  of 
energy  in  some  form  or  other.  Work  must  be  done  and  a  body  that 
cannot  yield  energy,  accomplishes  neither  changes  nor  w^ork.  But 
since  the  law  of  the  conservation  of  energy'  applies  equally  to  all  living 
entities,  these  alterations  cannot  be  associated  with  a  gain  or  loss  in 

1  V.  Fiirth,  loc.  cit.;  Inagaki,  Zeitschr.  fur  Biol.,  xlviii,  1907,  313,  and  Meiggs, 
Am.  Jour,  of  Physiol.,  xxiv,  1909.  178. 

»  Brooks,  Am.  Jour,  of  Physiol.,  xvii,  1906,  218. 

^  Heinz,  Handb.  der  exp.  Path,  und  Pharm.,  i,  1905,  576. 


94  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

material.  It  merely  means  that  one  kind  of  energy  is  transformed 
into  another  without  actually  causing  a  change  in  the  total  amount 
of  the  energy  available  in  the  universe.  It  is  true,  however,  that  the 
proportion  of  "bound"  and  "free"  energy  does  not  remain  the  same; 
in  fact,  the  latter  invariably  diminishes  and  never  increases.  Like 
all  protoplasm,  muscle  tissue  contains  a  store  of  chemical  substances 
from  which  it  derives  its  necessary  energy.  When  stimulated,  certain 
chemical  processes  of  an  explosive  type  are  initiated  in  its  substance 
which  cause  its  potential  energy  to  be  converted  into  kinetic  energy. 
The  latter  presents  itself  as  mechanical  work,  heat  and  electricity, 
light  being  excluded  in  this  particular  case.  But  naturally,  the  re- 
lative amounts  of  these  three  forms  of  energy  must  vary  considerably, 
the  production  of  heat  greatly  exceeding  that  of  mechanical  energy 
and  electricity.  Individual  variations  are  common  and  find  their 
origin  in  the  character  of  the  muscle  tissue  as  well  as  in  the  conditions 
under  which  it  is  made  to  contract.  Thus  we  find  that  the  muscles 
of  warm-blooded  animals  are  able  to  do  twice  as  much  work  per  unit 
of  mass  as  those  of  cold-blooded  animals  and  that  the  muscles  of  in- 
sects are  even  more  powerful  than  these.  It  has  already  been  men- 
tioned that  red  striated  muscles  are  more  powerful  than  pale  muscles, 
the  greater  effectiveness  of  the  latter  lying  rather  in  their  quickness  of 
action  than  in  their  actual  strength.  The  Hberation  of  energy  is  af- 
fected unfavorably  by  fatigue,  low  temperatures,  a  high  humidity  of 
the  air,  a  poor  nutritive  condition  of  the  body,  and  other  factors.  In 
general,  however,  it  may  be  said  that  about  one-third  of  the  total 
amount  of  energy  appears  in  the  form  of  mechanical  energy  and  some- 
what less  than  two-thirds  in  the  form  of  heat.^  Fick,-  working  with 
excised  muscles,  states  that  under  favorable  conditions  about  one- 
fourth  of  the  total  energy  can  be  given  off  as  mechanical  work,  pro- 
vided the  load  used  is  relatively  large.  With  smaller  weights  this 
amount  is  proportionately  diminished. 

The  Work  Performed  by  Muscle. — For  ordinary  purposes  it  suffices 
to  determine  the  work  performed  by  a  muscle  by  simply  multiplying 
the  load  by  the  height  to  which  it  has  been  lifted.  The  product  is 
then  expressed  in  terms  of  milligram-meters.  Thus,  if  a  muscle  raises 
a  weight  of  25  grams  to  a  height  of  10  millimeters,  as  determined 
by  the  weight  of  the  curve  recorded  by  it  upon  the  kymograph,  it  has 
done  250  gram-millimeters  of  work.  In  this  calculation,  however, 
an  allowance  must  be  made  for  the  magnification  of  the  writing  lever 
in  accordance  with  the  formula :  L  :  H  :  :  I :  h,  in  which  L  equals  the 
total  length  of  the  lever,  I  the  length  of  its  short  arm  from  the  axis 
to  the  attachment  of  the  muscle,  H  the  height  of  each  line  of  contrac- 
tion and  h  the  actual  height  to  which  the  load  has  been  lifted.  The 
work  (W)  is  then  computed  in  gram-millimeters  in  accordance  with 

1  Zuntz,  Pfliiger's  Archiv,  Ixviii,  1897,  19L 

2  Ibid.,  xvi,  1878,  85. 


THE    PRODUCTION    OF    ENERGY    IN    MUSCLE  95 

the  formula :  W  =  wh,  in  which  w  signifies  the  weight  and  h  the  height 
to  which  it  has  been  raised. 

From  these  residts  it  may  be  gatheretl  first  of  all  that  the  product 
must  become  zero  if  no  weight  at  all  is  attached  to  the  muscle.  When 
not  loaded,  therefore,  a  muscle  does  practically  no  external  work  and 
the  chemical  changes  occurring  during  its  contraction  are  almost 
wholly  converted  into  heat  and  a  small  amount  of  electricity.  The 
word  "practically"  is  inserted  here,  because  a  muscle  even  when  not 
carrying  a  weight,  must  overcome  its  own  resistance  which,  to  be  sure, 
is  so  slight  that  nearly  all  of  its  energy  can  appear  as  heat.  This 
modification  could  of  course  be  rendered  superfluous  by  adjusting  the 
muscle  in  a  horizontal  manner  and  immersing  it  in  oil  to  overcome  this 
friction  as  much  as  possible.  In  the  second  place,  it  is  also  evident  that 
the  product  must  become  zero  if  H  equals  zero,  and  even  when  the 
muscle  is  loaded  with  so  heavy  a  weight  that  it  is  quite  unable  to  lift  it. 
As  in  the  preceding  case,  most  of  the  energy  liberated  is  then  turned 
into  heat. 

Attention  should  also  be  called  to  the  fact  that  a  muscle  which 
merely  contracts  and  relaxes,  raising  and  lowering  a  weight,  really 
furnishes  no  energy  to  its  surroundings,  because  it  develops  no  kinetic 
energy  at  this  time.  In  order  to  accomplish  actual  work,  it  would  be 
necessary  for  it  to  produce  certain  changes.  This  end  it  could  easily 
accomplish  by  raising  a  weight  to  a  definite  height  and  permitting  it 
to  fall  to  the  surface  of  the  earth.  The  potential  energy  stored  in  it 
would  then  be  converted  into  kinetic  energy. 

We  have  previously  seen  that  a  muscle,  when  properly  counter- 
poised and  made  to  react  successively  against  a  steadily  increasing 
load,  exhibits  a  gradual  decrease  in  the  height  of  its  contractions. 
Eventually  a  weight  will  be  found  which  it  is  quite  unable  to  lift.  At 
this  time,  therefore,  the  load  counteracts  the  contractile  power  of  the 
muscle  and  no  mechanical  energy  is  liberated.  This  weight  which 
merely  places  the  muscle  under  a  maximal  degree  of  tension  and  does 
not  permit  it  to  change  its  length,  has  been  designated  by  Weber  as  the 
absolute  poiver  of  the  muscle.  Moreover,  since  this  power  is  propor- 
tional to  the  cross-section  of  the  muscle,  we  are  in  a  position  to  obtain 
a  standard  by  simply  determining  the  absolute  force  for  one  square 
centimeter  of  muscle  substance.  This  value,  to  be  sure,  differs  in 
different  muscles,  because  such  factors  as  the  character  of  the  myo- 
plasm  and  the  number  and  arrangement  of  the  muscle  fibers,  give  rise 
to  individual  variations.  For  frog's  muscle,  values  ranging  between 
0.7  and  3.0  kilograms  per  centimeter  of  cross-section  have  been  found. 
The  experiments  upon  human  muscles  have  been  made  during  volun- 
tary contractions  and  not  during  artificial  tetanization,  while  the  cross- 
sections  of  the  muscles  employed  for  these  tests  have  been  determined 
upon  dead  subjects  of  the  same  physique  as  the  person  experimented 
upon.     Hermann^  gives  the  average  absolute  force  of  human  muscle 

1  Pfliiger's  Archiv,  Ixxiii,  1898,  429. 


96 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


as  6.25  kilograms,  a  value  which  is  considerably  higher  than  the  pre- 
ceding one  for  frog's  muscle.  This  calculation  becomes  of  practical 
value  in  testing  the  power  of  the  muscles  of  persons  suffering  from 
various  types  of  nervous  diseases.  A  so-called  dynamograph  is  com- 
monly used  for  these  determinations.  This  instrument  consists  of  a 
tension-spring  against  which  the  muscles  of  the  hand  are  voluntarily 
contracted. 

A  close  study  of  the  curve  represented  by  Fig.  43  also  shows  that  a 
muscle  reacts  better  when  a  slight  load  is  attached  to  it  than  when  it  is 
not  weighted  at  all.  To  begin  with,  therefore,  the  contractions  in- 
crease in  height,  quickly  at  first  and  then  more  slowly,  until  a  certain 


Fig.  52. — Diagram  of  Work-adder. 
A,  wheel  which  is  turned  by  muscle  M  in  direction  of  arrows, 
by  brake  B.     Each  contraction  of  muscle  raises  weight  W . 


It  is  held  in  place 


maximum  has  been  reached.  Subsequent  to  this  point  the  increasing 
loads  gradually  diminish  the  contractions  until  the  muscle  is  no  longer 
able  to  raise  the  lever  above  the  abscissa.  Hence,  a  muscle  yields 
maximal  work  only  when  made  to  act  against  a  certain  moderate 
weight  which  places  it  under  a  physiological  tension. 

In  order  to  determine  the  work  performed  by  a  muscle  during  a  long 
period  of  time,  it  becomes  necessary  at  times  to  employ  an  ergograph 
or  a  work-adder.^  The  former  instrument  has  been  described  in  an 
earlier  chapter.  The  latter  consists  of  a  small  windlass  which  the 
muscle  (Tlf )  turns  slightly  in  one  direction  with  each  contraction.  The 
weight  (TF)  which  is  suspended  from  the  wheel  (^)  by  a  thread  is 
*  Fick,  Unters.  aus  dem  physiol.  Lab.  der  Ziiricher  Hochschule,  Wien,  1869. 


THE    PRODUCTION    OF    ENERGY   IN   MUSCLE  97 

raised  a  certain  distance  with  every  contraction,  its  (l(>scent  being 
guarded  against  by  an  automatic  brake  (B)  which  retains  the  wheel 
in  its  newly  accjuired  position  during  the  sulisequent  resting  period  of 
the  muscle.  At  the  end  of  this  experiment  the  total  work  performed 
by  the  muscle,  may  be  computed  by  multiplying  the  weight  by  the 
height  to  which  it  has  been  raised. 

The  Muscle  as  a  Thermogenic  Organ. — We  have  seen  that  the 
largest  amount  of  the  energy  liberated  by  the  body  leaves  it  in  the 
form  of  heat.  We  are  also  justified  in  concluding  that  this  heat  is 
derived  very  largely  from  the  activity  of  the  musculature,  because  the 
latter  constitutes  about  40  per  cent,  of  the  total  weight  of  the  body  and, 
after  the  removal  of  the  skeleton,  more  than  50  per  cent.  The  bones, 
as  may  readily  be  surmised,  do  not  possess  a  vivid  metabolism,  while 
that  of  the  muscles  is  greater  than  that  of  any  other  tissue.  Thus, 
it  is  a  matter  of  commori  experience  that  the  temperature  of  the  body 
increases  very  markedly  during  exercise,  frequently  to  39°  or  40°  C, 


Fig.  53. — Arrangement    of    Thermoelectric    Elements    (A    and   B)    and   Gal- 
vanometer C. 

but  this  rise  is  only  temporary  in  its  nature,  because  the  heat  is  again 
dissipated  during  the  subsequent  period  of  relative  muscular  rest. 
The  production  of  heat  may  also  be  registered  locally  in  the  contract- 
ing muscles  of  the  thigh  or  arm  of  a  mammal,  the  bulb  of  a  thermom- 
eter being  pushed  in  among  the  muscle  fibers  (Gierse,  1842).  More 
exact  values,  however,  may  be  obtained  with  the  help  of  thermoelec- 
tric elements,  but  naturally,  the  thermoelectric  method  necessitates  a 
much  greater  experimental  aptitude  than  the  thermometric. 

A  thermoelectric  couple  consists  of  two  dissimilar  metals,  such  as  German 
silver  and  iron  or  antimony  and  bismuth  {A  and  B).  These  are  soldered  together 
and  the  binding  post  upon  each  couple  connected  with  a  low  resistance  galvanom- 
eter (C).  In  investigating  the  heat  production  of  muscle,  one  of  these  couples  is 
inserted  with  its  pointed  tip  in  an  indifferent  muscle,  while  the  other  is  placed  in 
the  muscle  to  be  experimented  upon.  As  long  as  this  muscle  remains  inactive,  it 
generates  no  heat,  and  hence,  no  electric  differences  are  developed  at  the  points  of 
soldering.  The  needle  of  the  galvanometer  remains  stationary.  If  the  muscle  is 
now  made  to  contract,  this  system  immediately  ceases  to  be  isoelectric,  because  the 
heat  produced  therein  generates  an  electric  difference  in  the  corresponding  ther- 
mopile which  in  turn  leads  to  a  definite  deflection  of  the  galvanometric  needle. 
7 


98  PHYSIOLOGY   OF   MUSCLE    AND    NERVE 

B.v  equipping  this  indicator  with  a  small  mirror,  a  beam  of  light  may  be  reflected 
from  it  upon  a  screen  or  into  a  photographic  camera.  Its  excursions  are  standard- 
ized with  the  help  of  a  very  sensitive  thermometer. 

Becquerel  and  Bichet  (1835)  who  first  emploj'ed  this  method  upon  the  biceps 
muscle  of  a  human  subject,  obtained  a  rise  of  0.5°  C.  during  energetic  movements. 
In  a  similar  way,  Helmholtz  (1847)  has  found  that  the  tetanization  of  a  frog's  mus- 
cle raises  its  temperature  0.14-0.18°  C,  while  Heidenhain^  has  noted  a  rise  of 
0.005°  C.  during  single  contractions.  It  must  be  remembered,  however,  that  even 
a  resting  muscle  serves  as  a  thermogenic  organ,  because  the  blood  returned  from 
it  possesses  a  higher  temperature  than  that  passing  into  it  (Ludwig,  1881).  In 
addition,  it  has  been  ascertained  that  the  heat  production  varies  directly  with  the 
intensity  of  the  chemical  changes.  A  strong  stimulus,  therefore,  must  yield  more 
heat  than  a  weak  one.  Tension  has  a  similar  influence,  because  isometric  contrac- 
tions are  followed  bj'  a  greater  liberation  of  heat  than  isotonic.  Weight  acts  favor- 
ably at  first,  on  account  of  its  initial  tendency  to  augment  the  mechanical  energy; 
later  on,  however,  the  liberation  of  heat  diminishes  more  rapidly  than  the  amount 
of  work.  These  and  other  facts  tend  to  show  that  a  muscle  works  more  economic- 
ally when  acting  against  a  moderate  load  than  when  not  weighted  at  all.  Further- 
more, when  a  fresh  muscle  and  a  fatigued  muscle  are  made  to  perform  the  same 
amount  of  work,  the  former  generates  more  heat  than  the  latter,  because  it  is 
in  possession  of  a  greater  store  of  chemical  substances. 

The  Muscle  as  an  Electrogenic  Organ. — The  electrical  current 

generated  b}-  a  battery  finds  its  origin  in  chemical  changes  enacted  by  its 
constituents.  In  quite  the  same  way,  the  differences  in  electrical  poten- 
tial developed  by  muscle  and  other  forms  of  protoplasm,  find  their 
cause  in  chemical  alterations  accompanying  their  activity,  and  hence, 
are  derived  from  their  stored  potential  energy.  The  amount  of  elec- 
trical energA"  developed  by  muscle  is  rather  small,  but  it  should  not  be 
forgotten  that  this  amount  is  considerably  augmented  by  the  sum 
total  of  the  electricity  which  is  evolved  by  the  glands,  nervous  struc- 
tures and  other  tissues.     The  final  result,  therefore,  is  far  from  trivial. 

It  need  scarcely  be  mentioned  that  certain  animals,  for  example,  the  electric 
fish,  possess  special  organs  for  the  generation  of  this  form  of  energy  to  serve  as 
a  weapon  of  offense  and  defense.  It  is  stated  that  Malapterurus  electricus  inhabit- 
ing the  rivers  of  Africa  (Nile),  is  capable  of  producing  a  shock  equaUing  200  volts. 
The  organ  itself  is  situated  directly  below  the  skin  on  each  side  of  the  body  and 
consists  of  a  number  of  membranous  plates  arranged  parallel  to  one  another.  In 
Gymnotus  and  Malapterurus  these  plates  are  placed  vertically  and  in  the  Torpedo 
horizontal  to  the  long  axis  of  the  body.  Each  organ  is  innervated  by  a  nerve  which 
subdivides  and  sends  branches  to  each  plate.  In  Malapterurus  this  nerve  is  but  a 
single  giant  fiber  possessing  a  very  thick  investment  and  derived  from  a  single 
large  ganglion  cell.  The  long  discussions,  whether  these  electrical  organs  consist  of 
modified  muscle  or  nerve  tissue  or  whether  they  are  embryologically  distinct,  have 
led  to  the  conclusion  that  those  of  Torpedo  and  Gymnotus  have  been  derived 
from  muscle  tissue,  while  that  of  Malapterurus  is  an  outgrowth  of  the  skin  glands. 

Schonlein  has  estimated  the  electromotive  force  of  an  entire  organ  of  the  Tor- 
pedo at  0.08  volt  for  each  plate;  hence,  it  equals  that  of  thirty-one  Daniell  ceUs. 
This  voltage  is  sufficient  to  kill  other  fish  and  animals  and  especially  because  it  is 
discharged  in  transverse  lines.  The  discharge  results  chiefly  in  a  reflex  manner  up- 
on mechanical  stimulation.  In  Malapterurus  the  shock  traverses  the  conductor 
in  a  direction  from  the  head  to  the  tail  of  the  animal  and  in  Gymnotus  from  the 

^  Mechanische  Leistung.  etc.,  Leipzig,  1864;  also  see:  Fick,  Myotherm.  Unter- 
Buchungen,  etc.,  Wiesbaden,  1889. 


THE    PRODUCTION    OF   ENERGY    IN    MUSCLE  99 

tail  to  the  head.  Peculiarly  enough,  the  fish  itself  is  fully  protected  against  these 
shocks,  a  fact  which  is  generally  referred  to  the  extremely  low  degree  of  irritability 
of  its  tissues. 

Animal  electricity,  or  as  it  is  known  in  Physics,  galvanism  was  dis- 
covered by  Alvisio  Galvani  in  1786.  In  the  course  of  his  experiments 
upon  the  influence  of  atmospheric  electrical  discharges  upon  animal 
life,  he  attached  the  leg  of  a  frog  to  a  copper  hook  and  placed  this 
preparation  upon  the  iron  railing  of  the  veranda  of  his  house.  When 
he  did  so,  the  muscles  twitched  violently.  He  explained  this  phenome- 
non by  saying  that  the  muscles  themselves  generate  electricity.  Volta, 
however,  gave  a  very  different  and,  as  it  finall5'  proved,  more  correct 
explanation  of  this  reaction.  He  assumed  that  whenever  two  dis- 
similar metals  are  connected  with  a  moist  conductor,  a.  difference  in 
electrical  potential  is  established  which  is  equalized  as  soon  as  these 
metals  are  joined.  Peculiarly  enough,  Galvani  not  onlj^  adhered  to 
his  former  contention,  but  endeavored  to  find  further  substantiation 
for  it.  He  placed  a  muscle  preparation  upon  a  glass  plate  and  brought 
the  end  of  a  freshly  cut  nerve  in  contact  with  its  surface.  Whenever 
contact  was  made  between  them,  the  muscle  twitched  violently.  He 
thus  became  the  discoverer  of  animal  electricity  after  having  just 
convincingly  recognized  contact  electricity. 

Methods  of  Detecting  Electrical  Variations  in  Muscle. — The 
existence  of  electrical  currents  in  the  tissues  of  animals  and  plants 
did  not  find  direct  proof  until  the  year  1824,  when  Schweigger  dis- 
covered the  multiplicator  and  Nobili  the  galvanometer.  A  few  years 
later,  Nobili  also  proved  that  "natural  currents"  occur  in  the  frog, 
which  pass  in  a  direction  from  the  foot  toward  the  head  of  the  animal. 

The  ordinary  form  of  galvanometer  consists  of  a  ring  magnet  which  is  suspended 
by  means  of  a  silk  fiber  and  rests  in  relation  with  a  number  of  vertical  coils,  each 
of  which  is  composed  of  many  windings  of  fine  copper  wire.  If  an  electric 
current  is  passed  through  this  system  of  wires,  the  neighboring  magnetic  field  is 
influenced  in  such  a  way  that  the  magnet  is  deviated  from  the  magnetic  meridian 
either  to  the  left  or  right  in  accordance  with  the  direction  of  this  current.  These 
deviations  are  registered  as  a  rule  by  equipping  the  pointer  or  needle  of  the  magnet 
with  a  small  mirror,  from  the  surface  of  which  abeam  of  light  may  be  reflected  upon 
a  screen  or  upon  sensitive  paper  contained  in  a  photographic  camera  (Thompson). 
In  order  to  protect  the  galvanometer  against  the  magnetism  of  the  earth,  two 
magnets  of  nearly  the  same  strength  are  placed  in  opposite  directions  near  the 
instrument.  As  the  magnets  tend  to  point  toward  the  poles,  they  oppose  one 
another  and  thus  compensate  in  part  for  the  earth's  magnetism.  The  Deprez 
d'Arsonval  galvanometer  embraces  certain  modifications  which,  in  addition  to  those 
just  mentioned,  diminish  the  disturbances  otherwise  prone  to  result  from  currents 
made  to  traverse  neighboring  circuits  for  purposes  of  light  and  electric  power.  The 
principal  element  of  this  instrument  is  a  wire  which  is  hung  between  the  poles  of  an 
electromagnet.  Inasmuch  as  this  wire  is  bent  upon  itself  to  form  a  spiral,  it  is 
not  deflected  laterally  but  is  merely  twisted  in  a  rotatory  manner.  Its  movements 
are  registered  by  a  mirror  from  which  light  is  reflected. 

An  instrument  of  similar  construction  but  capable  of  a  much  greater  rapidity 
of  motion,  is  the  string  galvanometer,  devised  by  Einthoven.  ^     It  consists  of  a  power- 

1  Arch,  intern,  de  Physiol.,  iv,  1906,  133,  and  Pfliiger's  Archiv,  Ixxii,  1908,  517. 


100 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


ful  electromagnet   possessing   the   shape   of   a  horseshoe.     A  delicate  thread  of 
silvered  quartz  or  platinum  is  suspended  in  a  vertical  direction  between  its  two 


Fig.  54. — D'Aksonval  Galvanometer  as  Modified  by  Rowland  With  Telescope 
FOR  Observing  Movements  of  Needle.      (Howell.) 


Fig.  55. — Schema  of  Galvanometer. 

n,  s,  North  and  south  poles  of  astatic  pair  of  magnets;  m,  compensating  magnet,  held 
by  friction  on  the  staff,  and  capable  of  being  approached  to,  or  rotated  mth  reference  to, 
the  suspended  magnet;  X  ,  mirror;  /,  fiber  supporting  the  magnets;  c,  c,  c,  c,  coils  of  wire 
to  carry  the  electric  current  near  to  the  magnets,  the  upper  coils  being  wound  in  the 
opposite  direction  to  the  lower;  c,  e,  non-polarizable  electrodes  applied  to  the  longitudinal 
surface  and  cross-section  of  a  muscle.     (ATnerican  Text-book  of  Physiology .) 

poles.     The  sides  of  these  poles  are  perforated  so  that  the  shadow  of  this  string  may 
be  reflected  upon  a  screen  or  upon  the  sensitive  paper  of  a  photographic  camera. 


THE    PRODUCTION    OF    ENERGY    IN    MUSCLE 


101 


If  an  electric  current  is  permitted  to  pass  through  it,  it  is  moved  laterally  in  a  line 
parallel  to  the  poles,  i.e.,  perpendicularly  to  the  lines  of  force  passing  between  the 
poles  of  the  magnet.  These  deflections  take  place  to  eitlier  side  in  accordance 
with  the  direction  of  the  current.  Contrary  to  the  d'Arsonval  galvanometer,  the 
deflections  of  this  string  are  not  mere  twists  hut  actual  lateral  deviations  which  can 
be  increased  and  decreased  by  varying  the  tension  placed  upon  the  string.  Know- 
ing this  tension,  or,  in  other  words,  the  resistance  of  the  string,  the  strength  of 
the  current  causing  its  deviations,  may  be  calculated  directly  from  the  size  of  the 
deflections.  The  string  galvanometer  permits  of  a  freedom  of  motion  which  the 
ordinary  forms  of  galvanometer  cannot  attain,  altho\igh  the  actual  sensitiveness 
of  the  latter  is  no  doubtgreatertlian  thatof  the  former.     Thus,  its  chief  character- 

1 


Fig.  56. — Eixthoven's   Strint,   Galvaxometer,  as  Modified  by  Cunningham, 
Williams   and  Hindle. 
The  front-cover  has  been  removed  to  show  the  position  of  the  string  between  the 
poles  of  the  magnet.      The  connecting  posts  lie  behind  the  hood  containing  the  string. 

istic  is  its  speed  of  reaction  which  enables  it  to  follow  the  electrical  variations  with 
an  almost  immeasurable  exactness. 

A  third  instrument  which  is  sometimes  used  for  the  detection  of  electrical  cur- 
rents of  animal  origin,  is  the  capillary  electrometer  (Lippmann,  1877).  A  glass  tube 
is  drawn  out  at  one  end  into  a  tube  of  capillary  size  and  is  filled  with  mercury  up  to 
and  beyond  the  point  of  entrance  of  a  copper  wire  (A).  This  tube  is  then  placed 
vertical  and  is  made  to  dip  into  a  cup-shaped  receptacle  which  is  filled  with  mer- 
cury and  is  pierced  by  a  copper  wire  (B).  A  small  quantity  of  dilute  sulphuric  acid 
is  now  placed  over  the  mercury  in  the  cup.  If  the  capillary  is  of  proper  size,  the 
mercury  does  not  flow  out,  but  is  held  at  a  definite  level.  By  compressing  a  small 
rubber  bulb  which  is  connected  with  the  up}Der  end  of  this  tube  (P),  the  mercury 
is  then  forced  downward  and  upward  a  number  of  times  until  the  lower  lumen 
of  the  capillary  tube  is  completely  filled  with  the  acid.  The  level  of  the  mercury  or 
meniscus  (M)  is  adjusted  under  the  objective  of  a  microscope  (L) ;  in  fact,  it  may 
be  projected  upon  a  screen  or  upon  sensitive  paper.     If  an  electrical  current  is  now 


102 


PHYSIOLOGY    OF    MUSCLE    AND    NERVE 


passed  through  these  conductors  by  way  of  the  two  copper  wires,  the  surface 
tension  of  tlie  mercury  is  changed,  forcing  the  meniscus  to  move  either  upward  or 
downward  in  accordance  with  the  direction  of  the  current.  If  its  point  of  entrance 
(anode)  is  below,  the  meniscus  moves  upward,  and  vice  versa. 

The  strength  of  this  electrical  current 
may  be  determined  by  noting  the  extent  of 
the  movement  of  the  meniscus,  because  a 
direct  relationship  exists  between  these  two 
factors.  It  may  also  be  measured  by  in- 
terposing a  resistance  in  the  circuit  outside 
the  electrometer  or  galvanometer  which  is 
just  sufficiently  powerful  to  force  the  menis- 
cus or  the  galvanometric  needle  to  assume 
its  normal  position.  At  this  very  moment 
the  resistance  neutralizes  the  current,  and 
hence,  the  number  of  ohms  necessary  to  ac- 
complish this  end  must  correspond  precisely 
to  the  difference  in  the  electrical  potential. 
Most  generally,  however,  we  make  use  of 
the  so-called  compensation  method  which  re- 
quires the  use  of  an  artificial  current  in  a 
direction  opposite  to  that  produced  by  the 
muscle.  This  end  may  be  attained  most 
easily  with  the  help  of  a  rheocord  (Fig. 
58),  consisting  of  a  certain  length  of  Ger- 
man silver  wire.  The  two  binding  posts  at 
the  ends  of  this  wire  (A  and  B)  are  brought 
into  connection  with  the  poles  of  a  battery 
cell.  The  circuit  of  the  electrometer  or  gal- 
vanometer (C)  with  its  muscle  preparation 
(M)  is  then  brought  into  relation  with  the 
resistance  wire  by  a  lead  from  one  of  its  posts, 
while  the  return  lead  is  effected  bj'  means 
of  a  post  which  may  be  pushed  back  and  forth  upon  the  wire.  By  moving  this 
sliding  post  (D)  nearer  to  or  farther  away  from  the  end  post  (B),  a  greater  or 
less  amount  of  the  current  generated  by  the  battery  is  allowed  to  oppose  the 


Fig.  57. — Capillary  Electrometer. 
A,  tube  and  B,  receptacle  filled 
•with  mercury;  M,  meniscus  of  mer- 
cury; L,  lens  of  microscope;  P,  tube 
leading  to  small  rubber  bulb  for  ad- 
justing meniscus. 


Fig.  68. — The  Simple  Rheocord. 
AB,  German  silver  wire;  C,  galvanometer;  M,  muscle;  D,  sliding  post;  K,  key. 

muscle  current  until  an  equalization  has  finally  been  attained.  Knowing  the 
strength  of  the  counter  current,  the  strength  of  the  muscle  current  may  be  deter- 
mined from  the  resistance  which  has  been  interposed,  i.e.,  from  the  position  oc- 
cupied by  the  sliding  post.  The  value  of  the  action  current  of  an  ordinary  muscle 
scarcely  exceeds  75  millivolts;  its  usual  strength  is  0.06-0.08  volt.^ 

^  Samjloff,   Pfluger's  Archiv,  Ixxviii,  1899,  1. 


THE    PRODUCTION    OF    ENERGY    IN    MUSCLE  103 

The  Character  of  the  Electrical  Variations  in  Muscle.  Current 
of  Injury  and  Current  of  Action. — If  a  perfectly  nornuil  resting  muscle 
is  connected  witli  two  non-pohirizable  electrodes  which  in  turn  com- 
municate with  a  galvanometer,  the  indicator  of  this  instrument  re- 
mains perfectly  stationary.  The  reason  for  this  is  that  an  uninjured 
and  inactive  muscle  is  isoelectric,  i.e.,  it  does  not  present  differences 
in  electrical  potential  which  could  give  rise  to  a  current  (Hermann). 
This  condition,  however,  does  not  prevail  if  a  muscle  is  isolated  in  the 
usual  way  and  is  then  removed  from  the  body,  because  it  is  scarcely 
possible  to  do  this  without  injuring  it.  On  being  connected  with  a 
galvanometer,  such  a  muscle  immediately  deflects  the  needle,  because 
it  is  no  longer  isoelectric.  A  current  is  set  up  in  consequence  of  these 
differences  which,  in  accordance  with  the  direction  of  the  deflection 
of  the  galvanometric  indicator,  passes  from  the  uninjuried  to  the  in- 


771 

Fig.  58a. — The  Current  of  Injury. 
M,  muscle;  G,  galvanometer;  J,  seat  of  injury. 

jured  portion  of  the  muscle  (Fig.  58).  Viewed  from  the  outside,  there- 
fore, the  uninjured  portion  of  a  muscle  is  positive  (anode)  and  the 
injured  portion  negative  (cathode).  But  inside  the  muscle,  the  current 
passes  from  the  injured  portion  to  the  uninjured,  so  that  the  former 
constitutes  its  positive  and  the  latter  its  negative  pole.  Most  com- 
monly, however,  we  characterize  this  current  as  galvanometrically 
negative,  because  notice  is  taken  only  of  its  direction  outside  the 
muscle.^  This  current  is  usually  referred  to  to-day  as  the  current 
of  injury,  although  Hermann  has  called  it  the  demarcation  current, 
and  Matteucci,-  the  current  of  rest.  The  latter  designation  has  its 
origin  in  the  fact  that  the  resting  muscles  of  the  thigh  of  the  frog  yield 
an  electrical  current  whenever  they  are  cut  across  transversely  and 
connected  with  a  galvanometer.  A  few  years  later,  however,  Du- 
Bois-Reymond^  proved  that  resting  muscles  are  isoelectric  and  that 
the  current  of  rest  is  really  a  current  of  injury. 

1  Biedermann,  Ergebn.  der  Physiol.,  ii,  1903,  173. 

2  Transact.  Acad,  des  sciences  de  Paris,  1838-42. 

3  Unters.  iiber  tier.  Elektrizitat,  Berlin,  1848. 


104  PHYSIOLOGY    OF    MUSCLE    AND    NERVE 

This  electrical  difference  persists  as  long  as  the  injury.  The  same 
conditions  prevail  in  a  degenerating  muscle,  its  degenerated  portion 
being  galvanometrically  negative  to  its  normal  portion,  but  naturally, 
these  differences  cease  as  soon  as  the  degeneration  has  progressed 
evenly  throughout  its  substance.  Dead  tissue  gives  no  current.  In 
order  to  obtain  the  current  of  injury  in  an  unmistakable  manner,  it 
is  best  to  employ  a  cylindrical  muscle  and  to  injure  it  by  cutting  trans- 
versely across  one  of  its  ends.  One  non-polarizable  electrode  is  then 
placed  against  this  cross-section,  while  the  other  is  adjusted  externally 
upon  the  equator  of  the  muscle.  In  explanation  of  this  current 
DuBois-Reymond  has  proposed  the  so-called  molecular  theory  which 
assumes  that  the  muscle  is  built  up  of  a  seiies  of  the  smallest  possible 
molecules  which  are  electrically  charged  and  are  surrounded  by  an 
indifferent  conducting  fluid.  These  individual  molecular  elements 
are  peripolar,  i.e.,  their  equatorial  zones  are  positive  and  their  polar 
zones  negative.  The  former  are  directed  toward  the  surface  and  the 
latter  toward  the  cross-section  of  the  muscle.  Hermann's^  explana- 
tion is  based  upon  the  so-called  "alteration  theory"  which  assumes 
that  muscle  tissue  develops  no  electrical  current  as  long  as  its  chemical 
constitution  remains  the  same  throughout  its  substance.  Electrical 
differences,  however,  arise  immediately  if  the  chemical  equilibrium  of 
any  of  its  zones  is  disturbed  either  by  injury,  degeneration  or  activity. 
Oker-Blum^  claims  that  these  differences  in  the  electrical  potential  of 
a  muscle  are  dependent  upon  its  varying  concentration  and  are  caused, 
therefore,  by  the  speed  of  movement  of  its  different  ionic  constituents. 
Bernstein^  refers  them  to  a  process  of  dissociation.  But  these  theories, 
as  well  as  the  one  advocated  more  recently  by  Overton''  are  altogether 
too  incomplete  and  indefinite  to  be  made  the  subject  matter  of  a  prof- 
itable discussion  for  students. 

In  1842  Matteucci  made  the  observation  that  if  the  sciatic  nerve 
of  one  leg  is  placed  upon  the  muscles  of  the  opposite  leg,  the  muscles 
of  both  legs  may  be  made  to  contract  by  simply  stimulating  the  sciatic 
nerve  on  the  normal  side.  This  experiment,  which  is  known  as 
the  "induced  contraction"  or  "secondary  tetanus,"  may  also  be  per- 
formed in  the  following  manner  (Fig.  59).  Two  muscle-nerve  prepa- 
rations {A  and  B)  are  placed  near  one  another  upon  a  glass  plate  in 
such  a  way  that  the  sciatic  nerve  of  muscle  B  rests  lengthwise  upon  the 
body  of  muscle  A .  If  the  nerve  of  muscle  A  is  now  stimulated  with  a 
weak  induction  shock,  the  reaction  involves  not  only  muscle  A  but 
also  muscle  B.  The  essential  point  to  be  remembered  about  this 
experiment  which  is  usually  designated  as  the  rheoscopic  frog  prepara- 
tion, is  that  muscle  B  is  not  stimulated  directly  by  the  current  applied 
to  nerve  A,  but  indirectly  by  the  "current  of  action"  generated  in 
muscle  A  in  consequence  of  its  contraction. 

1  Handb.  der  Physiol.,  Leipzig,  i,  1879,  235. 

2  Pfliiger's  Archiv,  Ixxxiv,  1901,  191. 

3  Ibid.,  xcii,  1902,  521. 

*  Sitzungsb.  der  ph.-med.  Gesellsch.,  Wurzburg,  1905. 


THE    PRODUCTION    OF   ENERGY    IN   MUSCLE 


105 


In  explanation  of  this  phenomenon,  it  shoukl  be  stated  first  of  all 
that  the  activ(>  portion  of  a  muscle  possesses  a  different  electrical  po- 
tential from  the  resting  portion.  Thus,  if  a  perfectly  normal  muscle  is 
brought  into  the  circuit  of  a  galvanometer  by  means  of  non-polarizable 
electrodes,  the  excitation  of  one  of  its  ends  immediately  produces  a  de- 
flection of  the  needle  (Fig.  60).  If  the  direction  of  this  deviation  is  now 
noted,  it  will  ])c  seen  that  the  current  flows  through  the  galvanometric 
circuit  from  the  unexcited  to  the  excited  portion  of  the  muscle.  Its 
resting  part,  therefore,  is  electropositive  to  its  contracting  part.  In- 
side the  muscle,  of  course,  the  current  flows  from  the  contracting  to 
the  resting  portion,  the  former  being  positive  and  the  latter  nega- 
tive. But,  as  has  been  stated  above,  we  usually  designate  the  direc- 
tion of  these  currents  in  accordance  with  their  flow  through  the 
galvanometer. 


-The  Rheoscopic  Frog 
Preparation. 
Muscle    A    stimulated    through  its  nerve 
at    (S,    generates    an    action    current    which 
causes  muscle  B  to  contract. 


Fig.  60. — Current  of  Action. 

M,  muscle;  G,  galvanometer;  5,  seat 

of  stimulation. 


In  accordance  with  these  results,  it  must  now  be  evident  that  the 
preceding  experiment  with  the  rheoscopic  frog  preparation,  actually 
proves  the  occurrence  of  an  electrical  variation  in  muscle  in  conse- 
quence of  its  activity.  Muscle  B  serves  in  this  case  the  purpose  of  a 
galvanometer,  because  its  contraction  indicates  that  such  a  current  is 
actually  present.  It  may  be  concluded,  therefore,  that  the  excita- 
tion of  nerve  A  gives  rise  to  a  contraction  of  muscle  A,  in  the  course  of 
which  an  action  current  is  set  up  in  its  substance  which  serves  as  a 
stimulus  for  nerve  B.  The  impulse  generated  in  the  latter  produces 
a  contraction  of  muscle  B.  The  function  of  muscle  A  with  regard  to 
muscle  B  may  therefore  be  hkened  to  that  of  a  battery.  In  order  to 
avoid  the  possible  criticism  that  the  activation  of  muscle  B  is  caused 
by  an  escape  of  the  current  used  to  stimulate,  it  is  advisable  to  subject 
nerve  A  to  mechanical  impacts,  or  to  modify  the  entire  experiment  by 
placing  nerve  B  lengthwise  upon  the  beating  heart  of  a  mammal.'- 
1  Kollicker,  Miiller's  Archiv,  vi,  1856,  528. 


106 


PHYSIOLOGY  OF  MUSCLE  AND  NERVE 


In  the  latter  case  the  muscle  twitches  with  every  systole  of  this  organ, 
thereby  proving  that  a  current  of  action  is  also  generated  in  cardiac 
muscle.^  Similar  currents  arise  in  glandular  tissue  during  active  secre- 
tion and  in  nerves  when  made  to  conduct  impulses.  This  phenom- 
enon also  manifests  itself  in  the  optic  nerve  when  the  retina  is  stimu- 
lated by  light. 

The  Different  Phases  of  the  Currents  in  Muscle. — If  an  injured 
muscle  is  brought  into  the  circuit  of  a  galvanometer,  the  needle  of 
this  instrument  is  deflected  almost  immediately  to  indicate  a  negativity 
in  the  region  of  the  injury.  The  indicator  remains  in  this  position  as 
long  as  the  injury  lasts.  The  current  of  injury,  therefore,  possesses 
only  one  period;  in  other  words,  it  is  monophasic  in  its  nature.     The 


Fig.  61. — Diagram  Showing  Diphasic  Character  of  Action  Current. 
Phase  /  and  Phase  //. 
A,  active  portion;  R,  resting  portion;  <S,  seat  of  stimulation;  G,  galvanometer, 
current  of  action  is  indicated  in  each  case  by  the  arrows. 


The 


current  of  action,  on  the  other  hand,  is  diphasic,  or  rather  poly  phasic, 
'because  the  muscle  contracts  not  only  in  the  region  stimulated  but 
successively  throughout  its  substance  (Fig.  61).  Inasmuch  as  this 
contraction  does  not  involve  its  different  segments  simultaneously, 
but  consecutively  in  the  form  of  a  wave,  the  electrical  variations  must 
display  a  similar  wave-like  character.  To  begin  with,  the  zone 
nearest  the  seat  of  the  stimulation  is  electronegative  to  the  resting 
zone  (Phase  I.)  A  moment  thereafter,  however,  the  wave  of  contrac- 
tion has  reached  the  opposite  end  of  the  muscle  (Phase  II),  whereas 
the  area  stimulated  first  has  become  inactive.  The  negativity  then 
becomes  centralized  in  the  region  far  away  from  the  seat  of  the  stimu- 
lation. In  order  to  follow  this  progressive  wave  accurately,  the  gal- 
vanometer must  first  execute  a  deflection  in  a  direction  indicating 
the  negativity  of  the  muscle  at  the  point  of  stimulation  and  immedi- 


^  The  action  current  of  the  heart  of  mammals  has  also  been  demonstrated  by 
A.  D.  Waller  with  the  help  of  the  capillary  electrometer,  and  by  Einthoven  by 
means  of  the  string  galvanometer. 


THE    PRODUCTION    OF   ENERGY    IN    MUSCLE  107 

ately  thereafter  a  deflection  in  the  opposite  direction,  to  prove  that 
the  distant  polo  of  the  muscle  has  now  become  active  and  negative. 

While  the  ordinary  tj-pe  of  galvanometer  is  sufficiently  sensitive 
to  perceive  these  electrical  variations,  its  action  is  altogether  too  slow 
to  follow  them  with  accuracy.  Although  less  sensitive;,  the  strong  gal- 
vanometer is  more  serviceable  for  these  tests,  because  it  possesses  a 
much  greater  motility.  There  is  one  way,  however,  in  which  even  the 
ordinary  galvanometer  may  be  made  to  indicate  the  current  of  action 
and  that  is,  to  cause  its  needle  to  be  deflected  first  of  all  by  the  current 
of  injury.  Thus,  if  one  of  the  non-polaiizable  electrodes  is  placed 
against  the  cross-section  of  the  muscle,  while  the  other  is  applied  to  its 
equatorial  surface,  the  galvanometric  needle  will  be  forced  to  assume  a 
fixed  lateral  position.  If  the  distant  non-injured  portion  of  this  muscle 
is  now  stimulated,  the  subsequent  contraction  of  this  region  must  give 
rise  to  a  negativity  which  travels  from  here  toward  the  other  end  of 
the  muscle.  As  this  contraction-wave  .and  its  negativity  passes  the 
plus  lead  of  the  current  of  injury,  it  reduces  this  positivity  and  causes 
the  needle  to  swing  toward  and  beyond  zero.  Inasmuch  as  the  needle 
is  deflected  at  this  time  in  a  direction  opposite  to  that  forced  upon  it  by 
the  initial  current  of  injury,  this  phenomenon  has  frequently  been 
designated  as  a  "negative  variation"  of  the  primary  demarcation 
current.  This  arrangement,  therefore,  permits  the  negativity  ac- 
companying the  wave  of  contraction  of  muscle,  to  neutralize  the  posi- 
tivity of  the  current  of  injury  in  the  equatorial  region  of  the  muscle. 
Whether  it  will  do  that  fully,  depends  upon  the  temperature  and  elas- 
tic tension  of  the  muscle,  but  we  might  say  that  under  favorable  con- 
ditions the  current  of  injury  may  equal  0.04  volt,  while  the  current  of 
action  may  amount  to  as  much  as  0.08  volt.^  Clearly,  the  distance  to 
which  the  needle  will  be  deflected  by  the  action  current  depends 
upon  the  strength  of  the  latter,  i.e.,  upon  the  measure  in  which  it  is 
able  to  neutralize  the  initial  current  of  injury. 

The  relationship  existing  between  the  wave  of  contraction  and  the 
current  of  action  has  been  studied  by  photographing  the  variations  of 
the  galvanometric  indicator  together  with  the  movements  of  two  levers 
placed  horizontally  upon  the  surface  of  the  muscle  near  the  non-polar- 
izable  electrodes.  It  may  be  inferred  that  these  two  factors  are  very 
closely  allied  to  one  another,  but  the  records  obtained  by  the  method 
just  mentioned,  indicate  that  the  electrical  changes  antecede  the  move- 
ments of  the  corresponding  lever  by  a  fraction  of  a  second.  Two 
views  may  therefore  be  formulated,  namely,  (a)  the  electrical  changes 
constitute  the  wave  of  excitation  in  consequence  of  which  certain  chem- 
ical alterations  are  instigated  which  eventually  give  lise  to  the  shorten- 
ing of  the  muscle,  or  (6)  the  electrical  differences  are  the  result  of  the 
chemical  changes  set  off  by  the  wave  of  excitation  and  are  the  fore- 
runner of  the  mechanical  effects.  It  is  quite  impossible  at  this  time  to 
decide  this  question  one  way  or  another. 

^  Piper,  Pfliiger's  Archiv,  cxxix,  1909,  145,  and  Jensen,  ibid.,  Ixxvii,  1899,  137. 


SECTION  III 
THE  PHYSIOLOGY  OF   NERVE 


CHAPTER  XI 
THE  NEURON  AND  ITS  CONDUCTING  PATHS 

The  Neuron. — The  entire  nervous  system  is  an  aggregate  of  an 
infinite  number  of  neurons  which  are  held  together  by  a  nervous 
supporting  framework  or  neurogha,  but  many  parts  of  it  also  contain 
cells  showing  a  different  histological  character.  Thus,  it  is  found 
that  the  spinal  cord  and  the  cerebrum  are  enveloped  by  protective 
membranes  which  are  made  up  of  connective  tissue,  and  contain  in 
addition  blood  vessels  and  lymph  channels  for  nutritive  purposes.  The 
element  which  we  are  chiefly  interested  in  at  this  time  is  the  neuron 
or  nerve-cell.  It  consists  of  a  cell-body  and  its  processes,  the  latter 
being  divided  into  dendrites  and  the  axon  or  neurit. 

In  spite  of  the  fact  that  the  neuron  is  developed  from  a  single 
embryonic  unit,  known  as  a  neuroblast,  the  adult  cell  presents  a  great 
variety  of  forms.  It  may  be  pyramidal,  oval,  round,  stellate  or 
spindle-shaped,  and  its  size  may  vary  from  10-150)u.  The  cyto- 
plasm of  each  cell  embraces  a  nucleus  with  its  nucleolus,  and  a  proto- 
plasm which  is  granular  in  some  places  and  striated  in  others.  The 
latter  contains  numerous  rounded  bodies  which  stain  deeply  with 
methylene-blue  and  other  dyes.  These  are  the  so-called  Nissl's 
granules.  Especially  at  the  poles  of  the  cell  the  cytoplasm  is  arranged 
in  a  distinct  fibrillar  manner,  and  is  extended  outward  in  the  form  of 
long  processes,  which,  as  has  just  been  stated,  are  classified  as  dendrites 
and  axons.  The  former  divide  very  frequently  and  irregularly,  and 
do  not  pass  far  away  from  the  cell-body.  Their  terminals  are  generally 
beset  with  short  stubby  processes,  known  as  the  lateral  buds  or  gem- 
mules.     They  impart  a  peculiar  uneven  appearance  to  these  processes. 

Each  cell-body  usually  gives  rise  to  several  dendrites  but  only  to 
one  axon.  The  latter  is  distinguished  from  the  former  by  its  much 
greater  length,  its  uniform  caliber,  its  smoothness  and  the  greater  di- 
rectness of  its  course.  It  gives  off  very  few  branches,  which  are  desig- 
nated as  collaterals,  and  exhibits  a  hyaline  consistency.  The  dendrites, 
on  the  other  hand,  are  not  sharply  differentiated  from  the  cell-body 
unless  they  are  long,  when  they  may  also  acquire  a  hyaline  appearance. 

108 


THE    NEURON    AND    ITS    CONDUCTING    PATHS 


109 


The  Function  of  the  Neuron. — We  shall  see  later  on  that  the  cell- 
body  is  the  nutritive  center  of  the  neuron,  because  its  destruction 
entails  the  disintegration  of  all  of  its  prolongations.  Its  purpose 
is  to  produce  the  nerve  impulse  and  to  convey  it  to  distant  parts.  The 
arrangement  in  each  n(uiron,  however,  is  such  that  it  can  conduct  in 
only  one  direction,  namely  from  the  dendrites  to  the  axon.  It  pos- 
sesses, therefore,  a  distinct  polarity, 
the  former  prolongations  being  the 
avenues  by  which  the  nerve  impulse 
is  received  and  the  latter  the  path 
by  which  it  is  conveyed  to  other  parts. 
The  general  arrangement  of  the 
neuron,  therefore,  depends  in  a  large 
measure  upon  the  connections  which 
it  must  establish  with  neighboring 
nerve-cells  for  functional  purposes. 

Neurons  are  usually  designated  as 
afiferent  or  sensory  and  as  efferent  or 
motor.  The  former  conduct  impulses 
from  the  periphery  to  the  center  and 
the  latter  from  the  center  to  the  peri- 
phery. Moreover,  since  several  neu- 
rons of  each  type  are  always  required 
to  cover  large  distances,  they  are 
commonly  arranged  in  series  and  are 
then  differentiated  from  one  another 
by  characterizing  them  as  neurons  of 
the  first,  second,  third,  and  so  forth 
order.  Just  how  many  of  them  are 
required  to  unite  two  widely  sepa- 
rated points  of  the  nervous  system 
differs  greatly.  Thus  it  is  said  that 
some  of  the  efferent  neurons  of  the 
spinal  cord  attain  a  length  of  0.5-1.0 
m.,  so  that  the  distance  between  the 
cortex  of  the  cerebrum  and  the  foot 
may  be  covered  by  no  more  than  two 
neurons,  their  relay  station  being 
situated  in  the  anterior  horn  of  the 
gray  matter  of  the  lumbar  cord.  On  the  afferent  side,  the  path  is 
less  direct  and  hence,  a  more  frequent  relaying  is  made  necessary. 
Thus,  a  sensory  impulse  generated  in  the  foot,  generally  requires  three 
or  four  consecutive  neurons  for  its  passage  into  the  cerebrum. 

Reflex  Action. —  The  simplest  relationship  between  these  afferent 
and  efferent  neurons  is  presented  by  the  so-called  reflex  circuit 
which  permits  of  the  occurrence  of  the  simplest  possible  reaction, 
known  as  the  reflex  act.     The  responses  executed  with  the  help  of 


Fig.  62. — M,  motor  neuron;  S, 
sensory  neuron;  M,  motor  end- 
organ;  S,  sensory  end-organ;  A,  axis 
cylinder ;  MS,  myelin  sheath ;  N,  neuro- 
lemma; C,  collateral;  CB,  cell-body; 
D,  dendrites;  Nu,  nucleus  and  nu- 
cleolus; R,  sensory  terminals. 


no 


THE    PHYSIOLOGY    OF    NERVE 


nervous  tissue,  are  divided  into  reflexes  and  voluntary  reactions.  The 
former  are  non-volitional  and  the  latter  volitional  in  their  nature; 
hence,  any  action  which  is  performed  without  the  intervention  of  the 
will,  is  a  reflex,  while  one  requiring  this  amplification,  is  a  voluntary 
reaction.  As  this  topic  will  be  dealt  with  in  greater  detail  in  a  later 
chapter,  it  may  suflftce  at  this  time  to  state  that  the  production  of  a 
reflex  necessitates  the  union  of  at  least  one  sensory  with  one  motor 
neuron.  This  union,  however,  is  not  effected  by  continuity,  because 
the  distributing  terminals  of  the  former  merely  lie  in  close  contact 
with  the  receptive  dendrites  of  the  latter  without  becoming  confluent. 

The  place  where  two  neighboring 
neurons  are  in  this  way  functionally 
united  is  known  as  a  synapse.  Most 
generally  these  synapses  appear  in 
the  form  of  short  arborizations  of  the 
sensory  terminals  around  the  bushy 
dendrite  of  the  adjoining  motor  cell. 
In  other  cases,  the  distributing  fila- 
ments are  prolonged  into  the  im- 
mediate vicinity  of  the  neighboring 
cell-body  which  they  surround  in  the 
form  of  a  closely  knitted  reticulum. 
In  still  other  synapses,  the  sensory 
terminals  twine  around  the  neigh- 
boring dendrite  and  invest  it  closely 
for  some  distance.^  Attention  should 
also  be  called  to  the  fact  that  the  sen- 
sory and  motor  neurons  present  cer- 
tain general  peculiarities  which  render 
them  better  adapted  for  their  manner 
of  conduction.  Thus  we  find  that 
the  cell-body  of  the  former  generally 
occupies  a  central  position,  while  that 
of  the  latter  is  situated  near  the  end  of 
the  neuron.  In  fact,  in  certain  sen- 
sory neurons,  the  cell-body  lies  at 
some  distance  from  the  main  conducting  path,  this  condition  being 
most  clearly  in  evidence  in  the  ganglia  of  the  posterior  spinal  roots  and 
those  of  the  cranial  nerves. 

Under  experimental  conditions  the  reflex  circuit  may  be  stimulated 
at  almost  any  point,  the  resulting  impulse  being  propagated  from  here 
toward  the  axon  terminals  of  the  efferent  neuron.  Under  normal  con- 
ditions, however,  the  excitation  is  most  generally  received  by  the 
radicles  of  the  afferent  neuron  which  are  modified  into  a  sense-organ. 
A  stimulus  brought  to  bear  upon  the  latter   gives  rise  to  an  impulse 

^  Ramon  Y.  Cajal,  Histologie  de  syst.  nerveux,  Paris,  1909,  and  Barker,  The 
Nervous  System  and  Its  Const.  Neurones,  New  York. 


Fig.  63. 

SO,  sensory  end-organ,  receptor; 
MO  motor  end-organ,  effector;  AN, 
afferent  neuron;  EN,  efferent  neu- 
ron; C,  center;  S,  synapse. 


THE    NEURON    AND    ITS    CONDUCTING    PATHS  111 

which  travels  over  the  afferent  conductor  to  the  motor  cell,  and  from 
here  over  the  efferent  path  into  the  terminals  of  the  axon  which  are 
modihed  to  form  a  motor  end-organ  in  close  alhance  with  the  tissue 
effecting  the  reaction.  Thus,  it  will  be  seen  that  a  reflex  circuit 
consists  of  a  receptor,  an  afferent  path,  a  center,  an  efferent  path  and 
an  effector.  In  accordance  with  the  different  kinds  of  responses,  the 
receptors  and  effectors  present  different  structural  and  chemical 
peculiarities.  For  example,  an  afferent  impulse  may  arise  in  the  tactile 
corpuscles  of  the  skin  and  eventually  give  rise  to  motion,  the  effector 
being  formed  in  this  particular  case  by  the  skeletal  musculature. 
But  the  impulse  may  also  be  generated  in  the  retina  of  the  eye  or  in 
the  organ  of  Corti  and  nevertheless  lead  to  motion.  This  list  might 
be  extended  almost  indefinitely,  because  besides  the  ordinary  responses 
of  skeletal  muscle,  a  large  number  of  reactions  are  also  brought  about 
with  the  help  of  smooth  muscle.  In  the  latter  group  are  to  be  placed 
the  vasomotor  and  pilomotor  actions,  as  well  as  the  movements  re- 
sulting in  the  domain  of  the  stomach,  intestine,  ureter  and  bladder. 
Another  group  of  very  important  sensory  impulses  produce  secretory 
effects.  But  quite  irrespective  of  the  character  of  the  reaction  it 
should  be  kept  in  mind  that  any  response  executed  in  consequence  of 
a  sensory  impression  without  the  intervention  of  the  will,  constitutes 
a  reflex. 

The  Structure  of  Nerves. — Each  neuron  is  to  be  regarded  as  an 
elongated  conductor,  but  naturally,  neurons  are  generally  combined 
into  groups  and  do  not  appear  singly.  In  the  central  nervous  system 
an  aggregation  of  the  cell-bodies  of  several  neurons  is  known  as  a 
nucleus  and,  in  the  peripheral  system,  as  a  ganglion.  Furthermore,  if 
a  group  of  cells  of  this  kind  regulates  a  certain  function,  it  is  designated 
as  a  center.  The  former  term,  therefore,  refers  to  an  anatomical 
entity  and  the  latter  to  a  functional  entity.  The  nerve-fibers  passing 
away  from  these  cell-bodies  are  generally  bound  together  into  bundles 
which  are  known  as  nerves.  A  nerve,  therefore,  represents  a  collection 
of  nerve-fibers  outside  the  central  nervous  system.  It  is  formed  in 
the  following  manner:  the  axon  passes  away  from  the  cone-shaped  pro- 
jection of  the  cell-body,  and  soon  becomes  enveloped  in  a  tubular 
membrane  which  constitutes  the  medullary  or  myelin  sheath.  In 
many  cases,  a  second  investment  is  found  externally  to  this  one 
which  is  known  as  the  primitive  sheath  or  neurolemma.  Having 
acquired  these  sheaths,  the  axon,  or,  as  it  is  now  called,  the  axis-cyl- 
inder, becomes  the  nerve-fiber.  Many  of  these  are  bound  together 
to  form  a  bundle,  and  many  bundles  to  form  a  nerve.  The  individual 
fibers  are  supported  by  a  fine  stroma  or  endoneurium.  The  connective 
tissue  investing  the  individual  bundles  of  fibers,  is  known  as  the  peri- 
neurium, and  that  surrounding  the  nerve  as  a  whole,  as  epineurium. 
When  a  nerve  divides,  one  or  more  of  its  bundles  of  fibers  separate 
from  its  main  trunk  in  the  form  of  a  branch.  It  frequently  happens, 
however,  that  these  branches  do  not  pursue  an  independent  course 


112 


THE    PHYSIOLOGY    OF    NERVE 


but  are  interwoven  with  neighboring  branches  into  an  intricate  net- 
work or  plexus.  When  the  individual  nerve-fibers  reach  the  end- 
organ,  they  subdivide  into  finer  threads,  or  fibrils.  In  the  vicinity  of 
the  end-organ  the  investing  membranes  disappear. 


Fig.  64. — A,  nerv'e  fibers  stained  with  osmic  acid,  showing  axis  cylinder,  medullary 
sheath  and  neurolemma;  B,  medullated  nerve  fiber,  showing  nodes  of  Ran\'ier;  X  660 
times.      (Schafer.) 

The  thickness  of  nerve-fibers  varies  between  less  than  2/x  and  more  than  20)u. 
Those  innervating  the  skeletal  muscles  are  large  and  possess  a  diameter  of  about 
14-19^.  While  these  differences  are  due  very  largely  to  the  fact  that  some  nerve- 
fibers  are  devoid  of  a  medullar}'  sheath,  it  must  be  remembered  that  even  the  axis- 
cylinders  vary  greatly  in  their  thickness.  Thus,  it  is  easily  apparent  that  the  axons 
arising  from  the  large  ganglion  cells  of  the  anterior  horn  of  the  spinal  cord,  possess 
an  especially  large  caliber.      Nerve-fibers  are  either  medullated  or  non-medullated 


THE    NEURON    AND    ITS    CONDUCTING    PATHS 


113 


and  maj"  or  may  not  be  enveloped  by  neurolemma.      A  typical  nerve-fiber  consists 
of  the  following  parts: 

1.  The  axis-cylinder  forms  the  central  core  of  the  fiber  and  about  one-half  of 
its  total  thickness.  It  appears  as  a  dim  or  faintly  granular  thread  which,  under 
the  influence  of  certain  reagents,  may  become  fibrillated.  This  peculiarity,  as 
will  be  shown  later  on,  is  one  of  the  important  contentions  of  the  fi})ri]lar  theory 
of  nerve  action.  Each  axis-cylinder  pursues  an  unbroken  course  to  the  end-organ 
where  it  divides  into  a  number  of  fibriila;  which  may  at  times  be  closely  interwoven 
with  one  another. 

2.  The  medullary  stcbstance  forms  a  close-fitting  jacket  around  the  axis-cylinder 
and  consists  of  a  network  of  neurokeratine,  the  meshes  of  which  contain  a  fatty 
material.  Under  normal  condit  ions  it  appears  as  a  continuous  layer  of  homogeneous 
substance  which,  after  fixation  or  even  while  still  in  the  body,  splits  up  into  seg- 
ments possessing  a  length  of  about  1  mm.     The  indentations  between  these  differ- 


FiG.  65. — Transverse  Section  of  a  Nerve   (Median). 
ep,  epineurium;  pe,  perineurium;  ed,  endoneurium.      (Landois  and  Stirling.) 

ent  segments  are  known  as  the  nodes  of  Ranvier.  They  do  not  implicate  the  axis- 
cylinder.  About  midway  between  two  neighboring  indentations  lies  the  nucleus, 
its  long  axis  being  directed  parallel  to  that  of  the  fiber.  Immediately  surrounding 
it  is  a  layer  of  undifferentiated  protoplasm  which  thus  appears  as  small  islands 
directly  underneath  the  neurolemma. 

3.  The  neurolemma  is  a  transparent  sheath  of  homogeneous  material  which 
retains  a  uniform  thickness  throughout,  with  the  exception  of  the  aforesaid  nodes 
where  it  is  augmented  by  cement  substance  and  lies  in  direct  contact  with  the 
axis-cylinder.  Staining  reagents  are  prone  to  enter  these  indentations  and  to 
progress  from  here  along  the  axis-cylinder.  As  far  as  the  relative  amounts  of  these 
substances  are  concerned,  it  might  be  mentioned  that  the  median  nerve  contains 
63  per  cent,  of  connective  tissue,  28  per  cent,  of  myelin  and  9  per  cent,  of  axis-cylin- 
der (Ellison). 

4.  The  end-organs  to  which  the  axis-cylinders  are  distributed,  vary  greatly  in 
their  structure  as  well  as  in  their  chemical  composition.  They  are  divided  first  of 
all  into  receptors  and  effectors.  Among  the  former  might  be  mentioned  the  retina 
of  the  eye,  the  organ  of  Corti  of  the  internal  ear,  the  olfactory  cells,  the  taste  buds, 
the  cutaneous  corpuscles  for  pressure,  pain  and  temperature  and  the  sensory 
spindles  of  striated  muscle  tissue.  Probably  the  best  known  motor  end-organ  is 
the  so-called  end-plate  of  striated  muscle.     It  appears  as  a  low,  conical  or  rounded 


114 


THE    PHYSIOLOGY    OF    NERVE 


swelling  at  the  junction  of  the  axis-cylinder  with  the  substance  of  the  muscle-fiber. 
At  this  point  the  former  loses  its  medullary  sheath  as  well  as  the  neurolemma,  these 
envelopes  becoming  continuous  with  the  sarcolemma  of  the  muscle  fiber.  The 
plates  themselves  appear  to  be  made  up  of  fibrillar  arborizations  and  possess  a 
faintly  granular  or  cloudy  appearance.  At  the  point  of  contact  with  the  myo- 
plasm,  the  arborization  is  more  dense  and  presents  a  coarse  granular  appearance, 
forming  what  is  kno\\'n  as  the  sole  or  bed  of  the  end-plate. 

The  Chemistry  of  Nerves. — The  composition  of  nerves  has  not 
been  studied  in  great  detail.  Whatever  data  we  possess  have  been 
derived  very  largely'  from  analyses  of  the  white  matter  of  the  cerebrum 
which,   of   course,   is  composed   almost  exclusively    of    nerve-fibers. 


Fig.  66. — End-plates;   Chlorid  of  Gold  Preparation  to  Show  the  Axis  Cylin- 
ders AND  Their  Final  Ramifications  of  FiBRiLLiE.      X  170.     (Szymonowicz.) 


The  proteins  are  abundant  and  especially  so  in  the  axis-cylinder.  One  of  these 
is  a  nucleoprotein  which  coagulates  at  56  to  60°  C.  There  are  also  present  certain 
globulins.  One  of  these  coagulates  at  47°  C.  and  the  other  at  70  to  7.5°  C.  Accord- 
ing to  Halliburton,'  the  .sciatic  nerve  is  made  up  of  0.5.1  per  cent,  of  water  and 
34.9  per  cent,  of  solids  of  which  the  proteins  furnish  29.0  per  cent.  The  nerves  of 
the  cold-blooded  animals  begin  to  lose  their  irritability  at  about  40°  C.  and  shorten 
more  and  more  as  the  temperature  rises. 

The  lipoids  are  also  very  abundant.  They  comprise  phosphatides,  such  as 
lecithin  and  kephalin,  galactosids  and  cholesterin  or  cholesterol  in  the  following 
proportion:* 

Medullated  Xon-medullated 

nerve  nerve 

Cholesterin 25 . 0  47 . 0 

Lecithin 2.9  9.8 

Kephalin 12.4  23.7 

Galactosids... 18.2'  6.0 

1  Arch,  of  Neurology,  ii,  1903,  727. 

*  Falk,  Bioch.  Zeitschr.,  xiii,  1908,  153;  and  Bang,  Ergebn.  der  Physiol.,  vi, 
1907,  131. 


THE    NEURON    AND    ITS    CONDUCTING    PATHS  115 

The  lipoids  are  found  chiefly  in  the  myelin  sheath,  hut  as  non-medullated  fibers 
also  contain  them,  they  are  not  restricted  to  this  particular  part  of  the  fiber. 
Medullated  fibers,  moreover,  contain  a  much  larger  (juantity  of  cerebrosids  tlian 
the  non-medullated,  while  the  latter  exceed  in  the  lipoids,  such  as  lecithin,  kephalin 
and  cholesterin.  Ordinary  fat  is  found  in  the  epineurium,  and  Rclatin  in  the  con- 
nective tissue  throughout  the  nerve.  Very  small  amounts  of  creatin,  xanthin, 
lactic  acid,  uric  acid  and  urea  have  also  been  detected.  The  quantity  oiinorganic 
salts  is  small,  amounting  to  only  about  1.0  percent,  of  the  total  solids.  Pota.ssium 
which  is  most  abundant,'  is  said  to  play  an  important  part  in  conduction.^ 

The  Function  of  Nerves. — In  the  lower  forms  in  which  nervous 

elements  are  not  present,  the  wave  of  excitation  is  propagated  to  other 
parts  of  the  relatively  small  organism  in  a  direct  way,  because  proto- 
plasm possesses  not  only  the  jiower  of  irritability  but  also  that  of  con- 
ductivity. In  a  measure  this  is  also  true  of  the  higher  animals,  but 
the  conduction  of  the  waves  of  excitation  must  here  assume  a  some- 
what different  character,  owing  to  the  minute  subdivision  of  the  body 
into  many  colonies  of  cells  which  are  frequently  widely  separated  from 
one  another.  Previous  to  the  discovery  of  the  nerves  it  was  believed 
that  these  impulses  pursue  a  direct  course  in  all  directions  through  the 
different  tissues,  but  we  now  know  that  long-distance  conduction  is 
effected  solely  with  the  help  of  nervous  tissue  which  is  especially 
suited  for  this  function  on  account  of  its  unusual  irritability  and  con- 
ductile  power.  Conduction,  therefore,  presents  itself  first  of  all  as  an 
intracellular  propagation  of  the  wave  of  irritability  and  secondly,  as  a 
transfer  of  this  wave  to  other  colonies  of  cells  elsewhere  in  the  body. 
The  result  of  this  transmission  of  an  excitation  depends  of  course  upon 
the  character  of  the  end-organ  with  which  the  nerve  is  connected,  as 
well  as  upon  the  functional  qualities  of  its  center.  Inasmuch  as  it  is 
the  function  of  the  nerve  to  conduct  impulses,  the  character  of  the 
energy  evolved  in  consequence  of  it,  must  therefore  be  wholly  dependent 
upon  the  effector  with  which  it  is  functionally  connected. 

Irreciprocal  Conduction. — The  preceding  discussion  has  brought 
out  the  important  fact  that  the  conduction  in  neurons  is  hreciprocal, 
i.e.,  it  takes  place  in  only  one  direction.  Thus,  an  impulse  passes 
with  greatest  ease  across  the  end-plate  into  the  muscle,  but  not  from 
the  muscle  into  the  axon  and  the  cell-body.  The  same  conditions 
prevail  in  the  synapse,  the  conduction  being  from  the  axon  of  one 
neuron  into  the  dendrites  and  cell-body  of  the  next.  This  "Law 
of  Forward  Direction, "  as  it  has  been  called  l)y  Sherrington,^  possesses 
a  physico-chemical  basis,  inasmuch  as  it  has  been  shown  that  the 
different  parts  of  the  neuron  are  not  built  up  of  the  same  chemical 
substances.  That  this  is  so  may  be  gathered  from  the  fact  that 
such  agents  as  curare,  nicotin,  atropin  and  adrenalin  do  not  affect  the 
neuron  uniformly  throughout  its  substance  but  only  in  particular 
places.     Curare,  as  has  been  pointed  out  previously,  selects  the  motor- 

1  Macallum,  Ergebn.  der  Physiol.,  vii,  1908. 

2  Macdonald,  Proc.  Royal  Soc,  Ixxvi,  1904-05,  322. 
*  Proc.  Royal  Society,  London,  lii,  and  following. 


116  THE    PHYSIOLOGY    OF   NERVE 

plates  for  its  point  of  attack,  while  nicotin  paralyzes  the  dendritic 
processes  of  the  cell-body  and  atropin  the  terminals  of  the  axon. 
Secondly,  it  is  a  well-known  fact  that  the  time  which  an  impulse  requires 
for  its  passage  through  a  neuron,  is  largely  taken  up  by  its  journey 
through  the  cell-body  and  the  end-plate.  In  the  latter,  for  example, 
the  delay  is  appreciable,  amounting  to  more  than  one  thousandth  of  a 
second.  Thirdly,  it  has  been  demonstrated  that  the  fatigue  of  muscle, 
resulting  from  excessive  indirect  stimulation,  makes  itself  felt  first 
of  all  in  the  end-plate  and  not  in  the  nerve-fiber  nor  in  the  muscle 
tissue.  These  and  other  facts  unmistakably  point  toward  the 
presence  of  a  third  substance  which,  strictly  speaking,  is  neither  nerve 
tissue  nor  muscle  tissue  but  a  modification  of  the  former.  It  is  usually 
designated  as  the  intermediary  or  receptor  substance.  It  is  conceivable 
that  the  constituents  of  this  substance  arrange  themselves  as  electro- 
lytes in  a  way  to  permit  of  the  passage  of  the  excitation  in  only  one 
direction.     This  is  true  of  the  end-plate  as  well  as  of  the  synapse. 

The  Function  of  the  Different  Parts  of  the  Nerve. — The  trans- 
mission of  the  wave  of  excitation  is  effected  by  the  axis-cylinder,  or 
rather,  by  the  neurofibrils  of  which  it  is  composed.  The  latter,  as 
has  previously  been  shown,  ramify  throughout  the  cytoplasm  and 
form  connections  between  the  different  poles  of  the  cell-body  and  its 
processes. 

The  myelin  sheath  is  said  to  possess  a  protective,  insulating  and 
nutritive  function.  The  first  assertion  finds  substantiation  in  the 
fact  that  the  medullary  sheath  is  composed  of  a  spongy  network  con- 
taining a  soft  fatty  material.  Thus,  if  a  nerve-fiber  is  torn,  droplets 
of  a  substance  will  be  seen  to  ooze  out  which  exhibit  a  double  outline 
similar  to  that  of  the  nerve-fiber  itself.  If  subjected  to  osmic  acid, 
these  globules  stain  black,  owing  to  the  reduction  of  the  osmium. 
Moreover,  the  cross-section  of  a  fiber  invariably  appears  as  a  heavy 
dark  ring  surrounding  a  light,  faintly  stained  central  area.  It  is  also 
a  well-known  fact  that  ether  and  other  solvents  are  capable  of  removing 
this  fat  at  least  in  part  so  that  the  fiber  assumes  the  appearance  of  a 
round  tubular  space  surrounding  the  axis-cylinder.  The  latter  may 
then  be  stained  with  carmin  and  other  dyes  to  render  it  more  conspi- 
cuous. It  seems,  however,  that  the  contention  that  the  myelin  sheath 
supports  and  protects  the  axis-cylinder  in  a  mechanical  way,  cannot  be 
emphasized  especially,  because  the  non-medullated  axons  of  the 
sympathetic  system  show  perfect  conduction.  Moreover,  axons  are 
never  medullated  throughout  their  entire  extent  but  lose  their  sheath 
near  the  cell-body  as  well  as  near  the  end-organ.  In  the  third  place, 
while  the  cerebrospinal  nerves  are  ordinarily  in  possession  of  such  a 
covering,  they  do  not  attain  it  simultaneously  but  at  different  periods 
of  embryonic  life.  In  fact,  in  some  animals,  such  as  the  rat,  this  sheath 
is  not  developed  until  several  days  after  birth.  Meanwhile  the  new- 
born animal  shows  perfectly  coordinated  movements.^ 

^  Donaldson,  Jour,  of  Comp.  Neurology,  xx,  1910,  119;  and  Ambronn  and  Held, 
Arch,  fur  Anat.  und  Physiol.,  1896,  208. 


THE    NEURON    AND    ITS    CONDUCTING    PATHS  117 

The  same  aifiuuicnt.s  may  be  advanced  against  the  view  that  the 
myehn  sheath  serves  as  an  insulator  to  prevent  the  overflow  of  an 
impiiLse  from  one  axis-cvHnder  to  another.  So  far  no  definite  proof 
has  been  furnished  for  the  contention  that  the  non-medullated  fiber 
conducts  less  efficiently  than  the  medullated.  It  is  frequently  held, 
however,  that  the  loss  of  coordination  resulting  in  the  course  of  mul- 
tiple sclerosis  of  the  cord,  is  due  to  the  destruction  of  the  myelin  sheaths 
of  these  fil)ers,  because  their  axis-cylinders  appear  to  be  perfectly  nor- 
mal. In  general,  however,  it  is  true  that  the  wave  of  excitation  is 
conducted  without  it  spreading  to  neighboring  fibers  by  contact.  Iso- 
lated conduction,  therefore,  is  the  rule. 

The  third  contention,  that  the  myelin  sheath  serves  as  a  nutritive 
medium  for  the  axis-cylinder,  is  based  upon  the  following  data.  It 
has  been  found  that  its  thickness  varies  directly  with  the  caliber  of  the 
axis-cylinder,  and  that  the  axons  of  the  projection  system  of  the  cere- 
brum are  the  thickest  of  all.  Moreover,  inasmuch  as  staining  reagents 
find  ready  access  to  the  axis  cylinder  through  the  different  indentations 
at  the  nodes  of  Ranvier,  it  has  been  supposed  that  the  nutritive  sub- 
stances select  the  same  course.  It  has  also  been  observed  that  the 
stimulation  of  a  nerve  is  followed  by  certain  structural  changes  in  the 
myelin  sheath,  consisting  in  a  widening  of  the  meshes  of  its  neurokera- 
tin framework.^  Medullated  fibers  are  also  said  to  be  more  irritable 
and  to  possess  greater  recuperative  powers  than  non-medullated. 
None  of  these  facts,  however,  is  sufficiently  definite  to  constitute  an 
actual  proof  of  the  aforesaid  view.  In  addition,  it  might  be  men- 
tioned that  the  axis-cylinder  and  the  myelin  sheath  have  really  a 
separate  origin,  because  the  former  is  an  outgrowth  from  the  cell- 
body,  and  the  latter,  from  the  mesoblastic  cells  surrounding  the 
axon.  This  histogenetic  peculiarity  is  also  betrayed  by  the  changes 
which  an  adult  nerve-fiber  undergoes  in  the  course  of  degeneration 
and  regeneration.  The  latter  prove  conclusively  that  the  axis-cylinder 
is  nourished  from  the  cell-body,  while  its  investments  derive  their 
nutritive  material  directly  from  neighboring  blood-vessels. 

The  neurolemma  is  generally  regarded  as  a  supporting  and  protect- 
ing membrane  and  plays  an  important  part  in  the  degeneration  and 
regeneration  of  nerve  tissue.  The  view  that  it  is  also  insulating  and 
nutritive  in  its  function  could  be  met  with  the  objections  enumerated 
previously. 

Degeneration  of  Nerve. — The  nerve-fiber  retains  its  normal  appear- 
ance and  function  only  as  long  as  it  remains  in  connection  with  the 
cell-body.  When  its  continuity  is  broken  by  cutting,  crushing,  heat- 
ing or  other  means,  the  fiber  loses  its  irritability  and  conductivity 
and  undergoes  very  characteristic  retrogressive  changes.  Directly 
after  the  injury,  however,  its  excitabilitj^  is  temporarily  increased  and 
especially  at  the  seat  of  the  trauma,  owing,  in  all  probability,  to  the 

1  Striibel,  Pfluger's  Archiv,  cxlix,  1912,  1. 


118  THE    PHYSIOLOGY    OF    NERVE 

development  of  a  current  of  injury.  At  this  time  a  gradual  retro- 
gression sets  in  which  terminates  eventually  in  a  complete  loss  of  irri- 
tability.^ The  interval  of  time  required  for  the  development  of  these 
changes  varies  in  accordance  with  the  type  of  the  animal,  the  con- 
dition of  the  nervous  tissue  and  the  severity  of  the  lesion.  In  warm- 
blooded animals,  for  example,  the  excitability  is  lost  in  from  2  to  4 
days,  while  in  cold-blooded  animals  it  generally  takes  a  much  longer 
time.  For  the  sciatic  nerve  of  the  frog  this  interval  is  usually  given 
as  33  days,  although  it  may  be  as  long  as  3  or  4  months.  Evidently, 
this  difference  is  dependent  upon  the  nutritive  condition  of  the  animal 
and  the  temperature,  because  the  degeneration  sets  in  much  sooner 
during  the  summer  and  frequently  progresses  at  this  time  with  a  speed 
equal  to  that  observed  in  the  mammals.  In  young  and  vigorous 
animals  its  progress  is  more  rapid.  It  should  be  remembered,  how- 
ever, that  the  development  of  these  changes  necessitates  the  complete 
separation  of  the  fibers  from  the  cell-body,  because  if  they  are  merely 
divided  and  their  ends  left  in  contact  with  one  another,  the  degenera- 
tion is  prone  to  assume  an  abortive  character.  The  irritability  then 
fails  to  decrease  and  besides,  the  morphological  changes  do  not  develop 
with  any  degree  of  definiteness. 

Degeneration  is  classified  as  primary,  secondary,  and  tertiary. 
The  'primary  type  involves  the  nerve-fibers  at  the  seat  of  the  injury 
and  affects  solely  those  internodal  segments  which  have  been  directly 
exposed  to  the  trauma.  Beginning  at  this  point,  the  degeneration 
first  progresses  outward  in  the  direction  of  the  conduction  of  these 
axis-cylinders  until  it  finally  involves  their  distalmost  branches. 
This  marked  implication  of  their  peripheral  stumps  constitutes  sec- 
ondary degeneration.  As  far  as  the  efferent  paths  are  concerned,  it  may 
be  inferred  that  their  destruction  must  render  the  effector  functionally 
useless,  because  its  separation  from  the  cell  shuts  out  those  central  dis- 
charges which  normally  keep  it  in  tonus  and  activate  it.  Thus,  while 
the  degeneration  of  nerve  really  ceases  in  the  end-plate,  it  also  impli- 
cates in  an  indirect  way  the  tissue  with  which  it  is  in  functional  rela- 
tion. The  latter  then  suffers  a  disarrangement  of  its  metabolism  in 
consequence  of  the  loss  of  the  usual  efferent  impulses.  Thus  it  may  be 
observed  that  the  destruction  of  a  musculomotor  nerve  is  invariably 
followed  by  atrophic  changes  in  the  muscle  innervated  by  it.  It  is 
noted  that  the  muscle  fibers  decrease  in  thickness,  and  that  their  cross- 
sections  lose  their  sharp  contours  and  fibrillar  appearance.  They 
eventually  assume  a  hyaline  appearance  and  become  widely  separated 
from  one  another  by  infiltrated  fat.  Very  similar  changes  result  in 
afferent  paths.  The  direction  of  the  degeneration  in  them  may  be 
either  centrifugal  or  centripetal  in  accordance  with  the  location  of  the 
cell-bodies. 

In  either  case  the  destruction  of  the  conducting  path  must  lead  to 
an  isolation  of  the  cell-body  and  its  dendrites,  thereby  rendering  the 
1  Waller,  Miiller's  Archiv,  1852,  392. 


THE    NEURON    AND    ITS    CONDUCTING    PATHS  119 

latter  functionally  useless.  This  enforced  inactivity  causes  the  cell- 
body  to  lose  its  irritability  and  to  undergo  very  characteristic  morpho- 
logical changes  which  present  themselves  as  an  initial  turgescence  and 
final  atrophy  of  its  cytoplasm  and  nuclear  material.  The  Nissl's  gran- 
ules become  indistinct  and  finally  disappear  so  that  the  cytoplasm 
assumes  a  more  homogeneous  character.  It  is  to  be  emphasized, 
therefore,  that  the  degeneration  begins  at  the  seat  of  the  trauma  and 
advances  from  here  in  a  peripheral  as  well  as  in  a  central  direction. 
It  involves  first  of  all  the  entire  distal  end  of  the  nerve  and  later  on 
also  its  central  stump,  inclusive  of  the  corresponding  cell-bo(hes  and 
their  dendrites.  The  degeneration  progressing  in  a  central  direction, 
is  commonly  designated  as  retrogressive  degeneration.  Lastly,  it  is  to 
be  noted  that  these  retrogressive  changes  do  not  stop  at  the  next 
synapse,  but  also  implicate  those  neighboring  neurons  which  arc  in 
functional  relation  with  the  neuron  primarily  affected  by  the  injury. 
The  cause  of  this  retrogression  must  again  be  sought  in  the  inactivity 
forced  upon  the  correlating  neurons  by  the  trauma  to  one  of  their 
series  This  type  of  degeneration  may  be  characterized  as  tertiary, 
because  it  is  not  the  direct  result  of  the  lesion,  but  develops  only  in 
the  course  of  time  in  those  neurons  which  formerly  acted  in  harmony 
with  the  injured  neuron. 

We  have  seen  that  neurons  are  arranged  in  such  a  manner  that 
their  axons  conduct  either  in  an  efferent  or  afferent  direction.  Inas- 
much as  the  degeneration  first  involves  that  segment  of  the  fiber  which 
has  been  disconnected  from  the  cell-body,  the  morphological  changes 
must  advance  along  an  efferent  fiber  in  a  direction  from  the  center 
toward  the  periphery.  In  an  afferent  fiber  conditions  are  not  so 
simple.  The  cell-body  is  situated  in  between  its  processes.  The  de- 
generation, therefore,  may  affect  either  its  distal  or  its  central  proc- 
esses. This  statement  will  be  more  easily  understood  if  a  brief  refer- 
ence is  made  at  this  time  to  the  so-called  Wallerian  law  of  degeneration. 
It  is  a  well-known  fact  that  the  anterior  roots  of  the  spinal  cord  are 
formed  by  axons  which  are  derived  from  large  ganglion  cells  situated 
in  the  corresponding  horn  of  the  gray  matter.  These  axons,  therefore, 
conduct  toward  the  periphery  and  are  wholly  efferent  or  motor  in 
their  function.  For  this  reason,  a  division  of  this  root  must  be  followed 
by  a  degeneration  which  progresses  outward  from  the  level  of  the  cut 
until  all  the  terminals  have  become  involved  (Fig.  67,  I).  The  central 
stump  of  this  root  as  well  as  the  corresponding  cell-bodies  and  their 
dendrites,  will  be  affected  in  the  course  of  time  by  retrogressive  degen- 
eration. The  posterior  root  of  the  spinal  cord,  on  the  other  hand,  is 
made  up  of  axons  which  arise  in  cells  situated  in  the  so-called  spinal 
ganglia.  Their  function  is  afferent  or  sensory,  and  hence,  their  direc- 
tion of  conduction  is  from  the  periphery  to  the  center.  This  fact 
implies  that  the  division  of  this  root  must  give  rise  to  a  degeneration 
involving  the  end  still  connected  with  the  cord  (Fig.  67,  II),  whereas 
its  other  end  which  has  remained  in  contact  with  the  ganglion,  under- 


120 


THE    PHYSIOLOGY    OF    NERVE 


goes  merely  a  gradual  retrogression.  The  peculiar  distribution  of 
these  fibers  also  permits  of  a  third  cut  being  made,  namely,  at  a  point 
distally  to  the  spinal  ganglion.  In  the  latter  case,  the  degeneration 
involves  the  distal  axons,  leaving  the  entire  posterior  root  intact  until 
subsequently  affected  by  retrogressive  changes  (Fig.  67,  III). 

Very  similar  conditions  prevail  inside  the  central  nervous  system. 
Thus,  it  may  be  noted  that  the  anterior  pyramidal  tracts  of  the  spinal 
cord  are  formed  by  axons  derived  from  cells  in  the  motor  area  of  the 
cerebral  cortex,  whereas  the  posterior  columns  are  made  up  of  axons. 


PR 
Fig.  67.  . 

Fig.  67. — The  Course  of  the  Degeneration  in  the  Roots  of  the  Spinal  Cord. 
AR,  anterior  root;  PR,  posterior  root;  I,  division  of  anterior  root;  II,  division  of 
posterior  root  centrally  to  ganglion;  ///,  division  of  posterior  root  distally  to    spinal 
ganglion.     The  degenerated  fibers  are  indicated  in  black. 

Fig.  68. — Diagram  to  Illustrate  the  Direction  of  Degeneration  in  Spinal 
Neurons. 

The  degenerated  portion  is  indicated  by  dotted  lines. 

the  cell-bodies  of  which  lie  either  in  the  spinal  ganglion  or  at  a  low 
level  of  the  cord.  The  former  are  motor  and  the  latter  sensory  in 
their  function.  Consequently,  a  division  of  the  spinal  cord,  say,  at 
the  level  of  the  first  thoracic  vertebra  must  be  followed  by  an  outward 
degeneration  of  the  pyramidal  tracts  and  an  inward  degeneration  of 
the  posterior  columns.  The  former  is  generally  called  descending 
and  the  latter  ascending  degeneration. 

The    Morphological    Changes    of    Degeneration. — ^The    foregoing 
discussion  must  have  shown  that  the  cell-body  is  the  nutritive  center 


THE    NEURON    AND    ITS    CONDUCTING    PATHS  121 

of  the  noiiron.  As  far  as  the  dendrites  and  axons  are  concerned,  it  is 
conceivable  that  they  are  nourished  by  neiiroplasmic  streams  from  the 
cell-body,  whereas  the  nutritive  supply  of  the  investments  is  derived 
from  neighboring;  blood-vessels  and  lymphatic  channels.  The  metab- 
olism of  both,  however,  depends  upon  the  functional  capacity  of  the 
neuron  as  a  whole.  The  cell-body,  therefore,  constitutes  the  trophic 
center  of  the  neuron  and  the  element  chiefly  concerned  in  this  func- 
tion is  the  nuclear  material.  This  deduction  may  be  justified  by  the 
analogy  that  the  survival  of  a  cell  depends  upon  the  preservation  of 
its  nuclear  substance.  Thus,  if  a  cell  is  divided  several  times,  its 
different  fragments  must  soon  disintegrate,  unless  a  sufficiently  large 
mass  of  the  nucleus  have  been  apportioned  to  each  of  them. 

In  describing  the  histological  alterations  occurring  in  a  disin- 
tegrating neuron,  attention  should  first  be  called  to  the  degeneration 
involving  the  fiber  separated  from  the  cell-body  and  secondly,  to  the 
retrogressive  changes  affecting  the  cell-body  and  its  dendrites.  Con- 
cerning the  former  it  should  be  noted  that  the  primary  degeneration 
remains  confined  to  the  seat  of  the  injury  and  advances  only  as  far 
as  the  second  or  third  node  centrally  and  distally  to  it.  The  stretch 
of  fiber  so  affected  measures  no  more  than  3.0  mm.  in  length.  From 
here  this  process  spreads  so  rapidly  that  it  becomes  practically 
simultaneous  throughout  the  distal  stump. ^  A  typical  Wallerian 
degeneration  is  initiated  by  a  loss  of  irritability  which  is  associated 
with  a  turgescence  and  a  fragmentation  of  the  axis-cylinders.  These 
changes  develop  two  or  three  days  after  the  injury.^  They  are  quickly 
followed  during  the  next  day  by  a  fragmentation  of  the  myelin  sheath. 
The  latter  breaks  up  into  ellipsoidal  segments  and  then  into  smaller 
drops,  each  of  which  contains  a  short  stretch  of  the  axis-cylinder 
appearing  as  a  complex  of  colorless  granules.  Naturally,  these  struc- 
tural alterations  of  the  myelin  substance  are  associated  with  certain 
chemical  changes  which  betray  themselves  by  its  different  staining 
qualities.^  This  particular  phase  of  the  degeneration  is  followed  by 
a  period  during  which  much  of  the  material  thus  formed  is  gradually 
absorbed  so  that  at  the  end  of  one  month  the  fiber  is  practically  with- 
out its  medulla.  Meanwhile,  the  nuclei  of  the  neurolemma  have 
greatly  increased  in  number  and  have  become  invested  by  a  layer  of 
protoplasm  which  thus  partially  occupies  the  place  of  the  absorbed 
myelin.  This  structure  is  known  as  the  "band  fiber."  Its  appearance 
is  of  course  very  different  from  that  of  a  normal  nerve-fiber  and  there 
is  sufficient  evidence  at  hand  to  prove  that  it  is  non-conductile. 

In  this  connection  it  should  also  be  mentioned  that  the  distal  and 
central  stumps  in  the  immediate  vicinity  of  the  lesion  are  frequently 
beset  with  neurofibrillar  outgrowths  from  the  axis-cylinder.  These 
rami,  however,  cannot  be  considered  as  indications  of  regeneration, 

^  Ranson,  Jour.  Comp.  Neur.  and  Psych.,  xxii,  1912,  487. 

2  Bethe  and  Monkeberg,  Arch,  fiir  mikr.  Anat.,  liv,  1899,  135. 

3  Mardi's  method  of  staining  with  osmium  after  treatment  in  a  chrome  solution. 


122  THE    PHYSIOLOGY   OF   XERVE 

because  the}'  again  disappear  in  from  three  to  eight  days  after  the 
injury  and  even  if  the}--  are  well  protected  by  a  tubular  investment  of 
fascia.  The  degeneration,  therefore,  ceases  with  the  formation  of  the 
band  fiber,  a  functionally  inert  strand  of  protoplasm.  The  central 
stump,  as  has  been  stated  above,  degenerates  in  a  typical  manner  only 
for  a  distance  of  two  or  three  nodes  of  Ranvier  and  hence,  only  those 
segments  are  involved  which  have  been  directly  exposed  to  the  trauma. 

In  addition,  it  has  been  noted  that  the  cell-body  of  this  neuron, 
as  well  as  such  neurons  as  are  in  functional  relation  with  it,  undergo 
certain  changes  which  are  arranged  collectively  under  the  name  of 
retrogressive  degeneration.  It  is  readily  conceivable  that  an  injury  to 
a  chain  of  neurons  must  subject  all  of  them  to  a  certain  inactivity  which 
is  accompanied  by  a  disturbance  of  their  metabolism.  The  cell-body 
becomes  swollen  and  finally  atrophies,  this  decrease  in  the  quantity  of 
its  cytoplasm  being  associated  as  a  rule  with  an  irregularity  in  the 
contour  of  the  nucleus  and  a  change  in  its  position  to  a  place  nearer 
the  surface  of  the  cell.  The  chromatin  material  gradually  disappears 
so  that  the  staining  power  of  the  cell  becomes  much  diminished,^  and 
the  more  so,  because  this  chromatolysis  also  affects  the  Xissl's  granules. 
It  has  also  been  shown  by  Dickinson-  that  many  of  these  cells  become 
vacuolar  and  may  indeed  be  completely  destroyed,  but  these  retro- 
gressive changes  require  a  relatively  long  time  for  their  completion. 

The  Morphological  Changes  of  Regeneration. — The  regenerative 
processes  set  in  whenever  the  continuity'  of  the  neurons  is  reestablished, 
provided,  of  course,  that  not  too  long  a  time  has  elapsed  since  the  in- 
jury. Thus,  if  a  nerve  is  cut  and  its  two  ends  are  again  brought  into 
contact  immediately,  the  resulting  changes  are  so  fleeting  that  they 
can  scarcely  be  regarded  as  typifying  Wallerian  degeneration.  Con- 
currently, it  may  be  assumed  that  a  degeneration  of  long  standing 
can  only  be  remedied  by  a  regeneration  occupying  a  correspondingly 
long  time. 

In  accordance  with  the  view  that  the  neuron  is  not  onl}'  the  struc- 
tural but  also  the  functional  unit  of  the  nervous  sj'stem,  it  is  commonly 
believed  that  the  regeneration  of  the  peripheral  ends  of  the  different 
fibers  can  only  be  effected  by  outgrowths  fiom  the  axis-cyhnders  of 
the  central  stump  (Ranvier).  These  neuroplasmic  proliferations  are 
said  to  seek  the  old  neurolemmal  sheaths  and  to  continue  through  them 
into  the  end-organs.  Opposed  to  this  view  is  the  one  which  holds 
that  a  functional  unit  necessitates  the  presence  of  a  number  of  neurons 
arranged  in  series.  In  accordance  with  this  conception,  it  is  held  by 
Bethe  and  others  that  the  neurolemma  is  composed  of  the  remnants 
of  the  neuroblasts  from  which  the  nerve-cells  have  originated.  The 
cutting  of  a  nei've,  therefore,  would  permit  these  elements  to  assume 
their  former  characteristics  and  to  give  rise  to  regenerative  changes  in 
the  different  fibers.     While  several  facts  might  be  mentioned  in  support 

^  Ranson,  Jour,  of  Comp.  Neur.  and  Psych.,  xvi,  1906,  265. 
*  Jour,  of  Anat.  and  Physiol.,  iii,  1869,  176. 


THE    NEURON    AND    ITS    CONDUCTING    PATHS 


123 


of  the  second  view,  it  will  !)(•  shown  later  on  that  the  former  concep- 
tion of  regeneration  is  the  more  correct. 

Assuming,  therefore,  that  the  regeneration  of  the  fibers  results 
in  consequence  of  a  central  proliferation  of  neuroplasmic  material,^ 
the  question  may  be  asked  whether  this  outgrowth  takes  place  from 
the  axis-cylinder  or  from  its  investments.     Briefly  stated,  it  appears 


69. — Histology  of  a  Degenerating  Nerve  Fiber.     (Howell.) 


that  this  process  begins  with  a  hyperplasia  of  the  neurolemma  at  the 
site  of  the  section  of  the  nerve,  and  while  the  central  as  well  as  the 
peripheral  stumps  participate  in  this  reaction,  the  principal  part  is 
played  by  the  former. ^  The  cytoplasm  surrounding  the  nuclei  of 
this  localit}^,  is  rapidly  increased  in  amount,  as  is  also  the  number  of 

Fk;.   7U.--i;.MBitYOxi(:  Fibers  in  a  Regenerating  Xekve.      (HoircU.) 

the  nuclei  themselves.  In  tiiis  way  numerous  protoplasmic  streamers 
are  developed  which  become  well  differentiated  in  the  course  of  from 
four  to  six  days  an>I  prograss  into  the  distal  stump,  where  they  form 
thickened  bands  of  cytoplasm  within  the  neurolemma!  sheaths.  The 
axis-cylinders  of  th'i  central  stump  follow  along  these  protoplasmic 
bridges  and  thus  close  the  defect.     In  many  cases  they  may  even  be 


Fig.  71. 


-A  Newly  Developed  Fiber  in  a  Regenerating  Nerve  Fiber. 
(Howell.) 


seen  to  penetrate  the  cicatricial  tissue  at  the  site  of  the  injury.  To 
begin  with,  these  axons  are  non-medullated  but  acquire  a  myelin  sheath 
in  the  course  of  from  five  to  six  weeks  (dog) — provided,  of  course,  that 
they  were  medullated  previously.  This  medullation  begins  proximally 
and  progresses  toward  the  periphery. 

A  continuity  having  been  established  in  this  way,  the  correspond- 
ing cell-bodies  and  their  collaborating  neurons  gradually  regain  their 

^  Purpura,  Archivio  ed  atti  della  Soc.  ital.  di  Chirurgia,  1909  and  1911;    also 
see:  Perroncito,  Mem.  del  R.  1st.  Lombardo  di  Sc.  et  Lett.,  xx,  1908. 
^  Kirk  and  Lewis,  Johns  Hopkins  Hosp.  Bull.,  xxviii,  1917. 


124  THE    PHYSIOLOGY    OF    NERVE 

normal  appearance  and  again  become  functional.  It  might  probably 
be  mentioned  that  this  regeneration  does  not  always  lead  to  a  reunion 
of  the  same  axis-cylinders;  in  fact,  a  union  may  be  effected  between  the 
central  and  distal  stumps  of  two  different  motor  nerves  or  their 
branches.  Quite  similarh^,  a  sensory  nerve  or  a  segment  thereof  may 
be  brought  into  functional  connection  with  a  motor  nerve.  Purpura, 
for  example,  has  obtained  good  functional  results  in  cases  of  paralysis 
of  the  face  by  joining  the  distal  end  of  the  facial  nerve  with  the  central 
end  of  the  spinal  accessory.  In  animals  the  latter  nerve  has  also 
been  united  with  the  vagus  nerve,  this  crossing  enabling  an  ordinary 
musculomotor  nerve  to  produce  an  inhibition  of  the  heart. 

Very  important  evidence  favoring  this  centro-peripheral  manner  of 
regeneration,  has  been  presented  by  Harrison.^  It  has  been  shown  by 
this  investigator  that  the  excision  of  the  neural  crest  in  the  larvse  of 
amphibians,  from  which  the  cells  of  Schwann  are  derived,  does  not 
hinder  the  development  of  the  axis-cylinders  but  prevents  their  ac- 
quiring medullary  sheaths.  It  has  also  been  demonstrated  that  nerve- 
cells  send  out  axis-cylinders  when  immersed  in  a  favorable  nutritive 
medium  and  that  nerve-fibers  are  generated  by  pieces  of  cerebellum 
and  spinal  ganglia  when  kept  in  a  culture  of  clotted  plasma.  Many 
of  these  axon  processes  attain  a  length  of  0.5  mm.  in  the  course  of 
48  hours. 


CHAPTER  XII 

THE  PHENOMENA  OF  CONDUCTION  IN  NERVE 

Irritability  and  Conductivity. — Under  normal  conditions  the  wave 
of  excitation  arises  at  one  pole  of  the  neuron  and  traverses  it  in  a 
definite  direction,  either  afferently  or  efferently.  Under  experimental 
conditions,  on  the  other  hand,  it  is  possible  to  bring  the  stimulus  to 
bear  upon  it  at  almost  any  point,  i.e.,  either  upon  its  cell-body,  its 
axon  or  its  end-organ.  But  the  reaction  remains  the  same  in  all  cases, 
a  motor  effect  resulting  from  the  excitation  of  a  motor  nerve  and  a 
sensation  from  that  of  a  sensory  nerve.  The  structural  element  pri- 
marily concerned  in  this  transmission  of  the  wave  of  excitation  is  the 
fibrillated  axis-cylinder  of  the  nerve-fiber  and  its  ramifications  inside 
the  cell-body. 

It  is  possible  to  differentiate  between  the  irritability  and  conductivity  of  nerve 
in  the  following  manner:  A  muscle-nerve  preparation  {M)  is  placed  horizontally 
upon  a  glass  plate,  the  nerve  (A'")  being  drawn  through  a  small  glass  chandler  {D), 
which  in  turn  is  connected  with  a  Kipp  apparatus  (C).  One  pair  of  electrodes 
are  adjusted  to  the  nerve  inside  this  chamber  (at  A)  and  another  pair  outside  of 

1  Harvey  Lectures,  New  York,  1909,  199. 


THE  PHENOMENA  OF  CONDUCTION  IN  NERVE 


125 


it  (at  B).  A  pole  changer  is  made  use  of  so  as  to  be  able  to  divert  the  current  in 
the  shortest  possible  time.  Provided  that  the  nerve  has  not  been  injured,  the  mus- 
cle reacts  when  stimulated  at  cither  point.  If  carbon  dioxid  is  now  i)ermitte(l  to 
flow  into  this  chamber,  the  stimulation  at  A  becomes  inefTcctive,  while  that  at  B 
persists.  This  procedure  nuiy  bo  repeated  a  number  of  times,  but  the  excitability 
of  the  nerve  returns  very  soon  after  the  carbon  dioxid  hasbeen  removed  from  the 
chamber.  It  seems,  therefore,  that  small  ciuantities  of  this  gas  destroy  the  irrita- 
bility of  the  nerve,  but  do  not  atTect  its  conductivity,  and  hence,  these  two  proper- 
ties may  be  said  to  occur  independently  of  one  another.  ^  If  vapors  of  alcohol  are 
now  introduced  into  this  chamber,  the  nerve 
loses  even  its  conductivity,  as  is  evinced  by 
the  fact  that  the  stimulation  at  B  is  now 
quite  ineffective.  In  a  similar  waj-,  it  may 
be  shown  that  ether  and  chloroform  diminish 
the  irritability  as  well  as  the  conductivity, 
but  the  former  more  intensely  than  the 
latter.  Furthermore,  it  may  be  observed 
that  when  the  effect  of  these  depressants 
wears  off,  the  conductivity  is  reestablished 
more  rapidly  than  the  irritability. 

The   Direction    of    Conduction. — 

In  studying  the  different  phenomena 
connected  with  the  conduction  of  nerve 
impulses,  it  is  customary  to  make 
use  of  a  musculomotor  nerve  which 
is  still  attached  to  its  muscle.  Nerves 
exhibit  no  visible  signs  of  their  ac- 
tivity, i.e.,  they  do  not  liberate  me- 
chanical energy  nor  do  they  generate 
heat  or  electricity  in  amounts  suffi- 
cient to  be  recognized  by  means  of 
our  unaided  sense-organs.  In  this 
case,  therefore,  the  muscle  serves  the 
purpose  of  an  indicator  of  the  activity 
of  the  nerve,  because  under  normal 
conditions  every  excitation  of  the  latter  gives  rise  to  a  muscular  con- 
traction. But  naturally,  before  this  effect  can  make  itself  felt,  the  wave 
of  excitation  must  have  been  transmitted  from  the  seat  of  the  stimula- 
tion to  the  motor  end-organ.  Conduction,  therefore,  is  the  specific 
function  of  nerve,  its  property  of  irritability  enabling  the  stimulus  to 
produce  certain  chemico-physical  changes  which  are  then  propagated 
onward  in  the  form  of  a  wave  of  excitation  or  nerve  impulse.  It  must 
also  be  evident  that  any  other  motor  mechanism  or  even  a  sensory 
nerve,  may  be  employed  for  these  experiments.  In  the  latter  case, 
however,  it  is  necessary  to  arrange  the  sensory  nerve  in  such  a  way 
that  it  can  give  rise  reflexly  to  a  motor  effect,  because  this  is  the  most 
convenient  way  of  proving  its  activity. 

The  preceding  discussion  pertaining  to  the  serial  arrangement  of 

1  Grtinhagen,  Pfliiger's  Archiv,  vi,  1872,  181;  and  Luchsinger,  ibid.,  xxiv,  1881, 
347. 


Fig.  72. — Conductivity    and 

TABILITY  OF  NeRVE. 

M,  muscle;  iV,  ner^^e;  D,  glass 
chamber;  C,  Kipp  apparatus;  A  and 
B,  electrodes  inside  and  outside  the 
gas  chamber. 


126  THE    PHYSIOLOGY    OF    NERVE 

the  motor  and  sensory  neurons,  must  have  shown  that  the  wave  of 
excitation  is  propagated  along  nerve-fibers  in  a  particular  direction, 
namely  from  the  receptor  to  the  effector.  Thus,  afferent  fibers  con- 
duct normally  in  a  centripetal  direction,  and  efferent  fibers  in  a  cen- 
trifugal direction.  This  constitutes  the  so-called  law  of  forward  con- 
duction. An  entire  nerve,  on  the  other  hand,  need  not  be  purely 
afferent  or  efferent  in  character,  but  may  be  composed  of  both  types 
of  fibers.  In  the  latter  case,  it  is  designated  as  a  mixed  nerve.  Its 
power  of  conduction,  however,  is  not  interfered  with,  because  a  spread- 
ing of  its  impulses  from  fiber  to  fiber,  is  not  possible  under  normal  con- 
ditions. Mixed  nerves,  therefore,  may  convey  centripetal  and  centri- 
fugal impulses  at  the  sam.e  time. 

If  the  substance  of  a  unicellular  organism  is  stimulated,  the  wave 
of  excitation  proceeds  from  the  seat  of  the  stimulation  in  all  directions. 
In  a  similar  way,  it  may  be  noticed  that  the  application  of  a  stimulus 
to  the  center  of  a  single  muscle-cell  is  followed  a  moment  thereafter 
by  a  contraction  of  its  two  ends.  The  results  obtained  with  nerve- 
fibers  are  practically  the  same,  but  naturally,  this  statement  applies 
only  to  nerves  which  are  tested  under  experimental  conditions.  Thus, 
the  stimulation  of  a  motor  nerve  manifests  itself  solely  by  a  peripheral 
reaction  in  spite  of  the  fact  that  the  wave  of  excitation  is  also  propa- 
gated in  a  centripetal  direction.  Quite  similarly,  the  excitation  of  a 
sensory  nerve  cannot  betray  itself  by  a  reaction  in  the  receptor,  but 
only  by  some  central  effect  which  in  time  may  lead  to  a  reflex  motor 
response.  It  is  evident,  therefore,  that  the  law  of  forward  conduction 
may  be  changed  by  experimental  means  into  a  law  of  double  conduc- 
tion. The  direction  of  the  conduction,  however,  is  not  dependent  up- 
on differences  in  the  substance  of  the  nerve-fiber,  but  solely  upon  its 
central  and  peripheral  connections.  The  irreciprocity  of  conduction, 
as  we  have  previously  seen,  is  wholly  determined  by  the  conditions 
existing  at  the  poles  of  the  neuron. 

The  fact  that  the  nerve  impulse  may  be  propagated  in  both  directions  is  most 
clearly  proven  by  the  following  experiment  (Fig.  73)  devised  by  DuBois-Rey- 
mond.^  Each  end  of  a  long  stretch  of  nerve  is  connected  with  the  poles  of  a  gal- 
vanometer. On  stimulating  the  nerve  about  midpoint  between  these  instruments, 
it  is  noted  that  both  needles  are  deflected.  For  the  present  this  phenomenon 
need  not  be  explained  further  than  to  state  that  the  passage  of  a  nerve  impulse 
gives  rise  to  an  action  current  which  betrays  itself  by  a  galvanometric  negativity. 
Inasmuch  as  this  negative  variation  appeared  at  both  ends  of  the  nerve,  it  must  be 
concluded  that  the  wave  of  excitation  has  progressed  in  this  case  in  a  central  as 
well  as  in  a  peripheral  direction.  It  is  also  to  be  noted  that  this  result  may  be 
obtained  not  only  with  mixed  nerves,  but  also  with  pure  afferent  or  efferent  nerves. 
Gotch  and  Horsley^  have  modified  the  foregoing  experiment  by  adjusting  a  galvan- 
ometer to  the  distal  end  of  one  of  the  divided  anterior  roots  of  the  sciatic  nerve 
of  the  cat,  and  by  subjecting  the  distal  trunk  of  this  nerve  to  repeated  stimulations. 
The  centrifugal  conduction  was  manifested  in  this  case  by  the  contraction  of  the 
leg  muscles  and  the  centripetal  conduction  by  the  deflection  of  the  needle  of  the 

1  Thierische  Elektrizitat,  ii,  1849,  587. 

2  Philos.  Transactions,  1891. 


THE  PHENOMENA  OF  CONDUCTION  IN  NERVE 


127 


galvanometer.  To  adjudge  this  result  correctly,  it  must  of  course  be  remembered 
that  the  anterior  roots  of  tlie  cord  are  motor  in  their  function;  i.e.,  they  conduct 
under  normal  conditions  in  a  centrifuj^al  direction.  Double  conduction  for  the 
afferent  fibers  was  proved  l)y  stimulatinp;  the  posterior  root  of  tlic  sciatic  nerve 
and  observinp;  the  deflections  of  a  galvanometer  adjusted  to  the  central  end  of  the 
peripheral  portion  of  this  nerve.  Tiie  posterior  roots  of  the  spinal  nerves  are 
sensory  in  their  function  and  conduct  under  normal  conditions  in  a  centripetal 
direction. 


; 


n 


n 


Fig.  73. — Conduction  in  Both  Dikections  in  Nerve. 

A',  nerve;  S,  point  of  stimulation;  A  and  B,  galvanometers  upon  the  two 

ends  of  the  nerve. 

Another  method  of  proving  double  conduction  in  nerve  has  been  devised  by 
Kiihne^  (Fig.  74).  It  has  previously  been  stated  that  several  of  the  long  muscles, 
such  as  the  gracilis  and  sartorius,  receive  their  nerve  supply  at  a  point  about  mid- 
way between  their  two  extremities.  The  nerve  entering  here  divides  into  two 
principal  branches  which  innervate  the  upper  and  lower  ends  of  the  muscle  respec- 
tively. If  the  muscular  continuity  is  now  broken  by  a  transverse  cut  into  the  tip 
of  the  triangle  formed  by  these  branches  (C),  the  upper  and  lower  ends  of  the  mus- 
cle {A  and  B)  will  be  practically  isolated  from  one  another  save  for  the  bridge  of 


Fig.  74. — Conduction'  in  Both  Directions  in  Gracilis  Muscle. 
A   and  B  segments  of  gracilis  muscle  divided  by  cut  C;  S,  point  of  stimulation; 
A'',  motor  nerve  and  its  branches. 

nerve-tissue.  If  the  distalmost  filaments  of  one  of  the  branches  of  this  nerve  are 
now  stimulated  {S),  the  muscular  contraction  immediately  ensuing  does  not  remain 
confined  to  this  half  of  the  muscle  (A)  but  also  involves  the  other  half  (B).  This 
fact  leads  us  to  infer  that  the  excitation  advances  first  of  all  in  a  centripetal  direc- 
tion over  the  fibers  of  the  corresponding  branch  (A)  and  then  spreads  over  the 
normally  centrifugal  fibers  to  the  distant  muscle-strip  B.  Thus,  the  normally 
efferent  fibers  inner\'-ating  the  end  A,  are  temporarily  converted  into  afferent 
fibers.  In  order  to  meet  the  possible  objection  that  this  result  may  be  caused  by  a 
direct  spreading  of  the  electrical  current  from  A  to  B,  the  stimulation  may  be 

^  Archiv  fiir  Anat.  und  Physiol.,  1859,  595. 


128 


THE    PHYSIOLOGY    OF    NERVE 


effected  by  simply  pinching  the  distal  filaments  of  the  nerve  with  forceps  or  by  cut- 
ting across  them  with  the  scissors. 

A  very  similar  relationship  exists  in  the  electrical  organ  of  Malapterurus.^  In- 
asmuch as  its  individual  membranous  plates  are  innervated  by  the  branches  of  a 
single  motor  nerve  (Fig.  75),  the  mechanical  stimulation  of  the  terminals  in  a 
single  plate  must  invariably  be  followed  by  a  discharge  of  the  entire  organ.  Clearly 
any  impulse  arising  peripherally  in  one  of  these  plates  {D),  can  only  be  trans- 
ferred to  the  adjoining  plates  {AB  and  C)  at  the  next  bifurcation,  and  hence,  the  im- 
pulse must  first  asecnd  along  the  normally  efferent  branch  before  it  can  spread  in  a 
centrifugal  direction  to  the  other  parts  of  the  organ.  This  peripheral  transfer  of 
impulses  is  made  possible  by  the  fact  that  the  individual  axis-cylinders  of  the  motor 
fibers  divide  when  in  close  proximity  to  the  end-organ  and  send  their  fibrillar  com- 
ponents in  different  directions  into  the  tissue. 
Consequently,  it  is  not  necessary  that  the  reversed 
impulse  be  transferred  to  a  neighboring  axis-cylin- 
der, because  it  can  reach  its  destination  through 
the  ■  fibrillse  of  the  same  axis-cylinder.  It  will  be 
seen,  therefore,  that  conduction  in  both  directions 
is  not  contrary  to  the  law  of  isolated  conduction. 

Different  investigators  have  also  sought  to 
prove  double  conduction  by  the  establishment  of 
a  primary  union  between  the  central  and  distal 
stumps  of  different  sensory  and  motor  nerves. 
Thus,  it  has  been  shown  by  Bidder  (1865)  that 
a  union  between  the  distal  end  of  the  hypoglossal 
(motor)  and  the  central  end  of  the  lingual  nerve 
(sensory)  eventually  permits  us  to  effect  move- 
ments of  the  tongue  by  stimulating  the  sensory 
lingual  nerve.  In  a  similar  way,  Budgett  and 
Green^  have  succeeded  in  cutting  the  left  vagus 
nerve  between  its  ganglion  and  the  cranium  and 
in  uniting  the  peripheral  stump  of  this  nerve  with 
the  peripheral  end  of  the  hypoglossal.  Some 
months  later  the  muscles  of  the  tongue  could  be 
made  to  contract  by  stimulating  the  peripheral 
end  of  the  vagus.  In  this  connection  brief  men- 
tion should  also  be  made  of  the  well-known  experi- 
ment of  Paul  Bert^  purposing  the  formation  of  a 
primary  union  between  the  tip  of  the  tail  of  a  rat  and  the  subcutaneous  tissues 
upon  the  dorsal  aspect  of  its  body.  The  process  of  healing  having  been  fully  com- 
pleted, the  tail  was  then  cut  off  near  its  base.  Inasmuch  as  the  stimulation  of 
the  former  base  of  the  tail  still  gave  rise  to  sensations  of  pain,  the  conclusion 
seemed  justified  that  nerve-fibers  conduct  centripetally  as  well  as  centrifugally. 
In  all  these  experiments,  however,  it  must  be  taken  into  account  that  the  cutting 
of  nerves  is  followed  by  degeneration  which  in  turn  is  succeeded  by  the  formation 
of  new  axis-cylinders.  For  this  reason,  it  cannot  be  held  that  the  inversion  of  a 
part  actually  leads  to  an  inversion  of  the  nerve-fibers  or  to  reversed  conduction. 
These  experiments,  therefore,  cannot  be  said  to  be  well  adapted  for  proving 
double  conduction. 

The  Speed  of  Conduction  in  Nerve. — Inasmuch  as  the  passage  of 
the  wave  of  excitation  is  not  associated  with  visible  changes,  it  was 
thought  at  first  that  the  rate  of  its  progression,  in  analogy  with  that  of 

1  Babuchin,  Archiv  fiir  Anat.  und  Physiol.,  1877,  262. 

2  Amer.  Jour,  of  Physiol.,  iii,  1899,  115. 
3Compt.  rend.,  Ixxxiv,  1877,  173. 


Fig.  75. — Conduction  in 
Both  Directions  in  the 
Electric  Okgan  of  Malap- 

TERURUS. 

N,  motor  nerve  and  its 
branches,  leading  to  plates  A 
B  C  and  D;  S,  stimulation  at 
D  produces  discharges  of  entire 
organ. 


THE    PHENOMENA    OF    CONDUCTION    IN    NERVE 


129 


light,  is  immeasurable.  But  this  view,  which  was  first  expressed 
by  Johannes  v.  Miiller,  in  1844,  could  not  be  maintained  for  any  length 
of  time,  because  already  in  1850  v.  Helmholtz^  d(! vised  a  method  which 
gave  fairly  accurate^  results.  In  brief,  it  (;()nsisted  in  deterniininjj;  the 
time  elapsing  between  the  application  of  an  electrical  stimulus  to  the 
nerve  of  a  nerve-muscle  preparation  and  the  moment  when  the  result- 
ing contraction  of  the  muscle  caused  the  circuit  of  a  galvanic  battery 
to  be  broken.  Very  clearly,  however,  this  interval  included  not  only 
the  time  occupied  by  the  passage  of  the  excitation  to  the  muscle,  but 
also  the  time  of  contraction  of  the  muscle  itself.  A  few  months  later 
Helmholtz  devised  a  second  method  which  is  not  only  much  simpler 
but  also  much  more  accurate  than  the  one  just  mentioned  (Fig.  76). 


Fig.  76. — Speed  of  the  Nehve  Impulse. 
M,  muscle  and  nerve  connected  with  writing  lever  W  and  two  pairs  of  electrodes 
N  and  F.     The  wires   from   inductorium   J  are  connected  with  the  pole  change  P,  so 
that  the  nerve  may  be  stimulated  either  near  to  or  far  away  from  the  muscle. 

A  nerve-muscle  preparation  (M)  is  connected  with  a  writing  lever  (T^^) 
in  the  manner  described  in  one  of  the  earlier  chapters.  The  nerve 
is  then  stimulated  either  at  a  point  far  away  from  the  muscle  (F) 
or  close  to  it  (A^).  In  each  case,  the  contraction  of  the  muscle  is  re- 
corded upon  a  swiftly  revolving  kymograph,  above  the  record  of  a 
tuning  fork  vibrating  in  hundredths  of  seconds  and  the  record  of  an 
electromagnetic  signal  indicating  the  precise  moment  of  stimulation. 
If  the  lengths  of  the  latent  periods  of  these  contractions  are  compared 
with  one  another,  it  will  be  found  that  those  obtained  by  stimulating 
the  nerve  far  away  from  the  muscle  (F) ,  are  appreciably  longer  than  those 
recorded  by  stimulating  the  nerve  near  the  muscle  (A').  The  differ- 
ence between  these  latent  periods  corresponds  to  the  time  consumed 
by  the  wave  of  excitation  in  its  passage  from  F  to  N.  This  distance 
having  been  determined  with  the  ruler,  the  time  may  then  be  calculated 
1  Monatsber.  d.  Berliner  Akad.,  1850. 


130  THE    PHYSIOLOGY    OF    NERVE 

which  the  impulse  requires  for  its  journey  through  this  particular 
stretch  of  nerve. 

The  values  which  Helmholtz  detained  varied  between  24.6  and 
38.4  m.  in  a  second,  the  determinations  being  made  at  temperatures 
varying  between  11°  and  21°  C.  At  the  average  temperature  of  the 
room,  the  velocity  for  the  musculo-motor  nerves  of  the  frog  may  there- 
fore be  said  to  be  about  28  m.  in  a  second.  By  recording  the  contrac- 
tions of  the  muscles  of  the  thumb  during  stimulation  of  the  median 
nerve  at  two  widely  separated  points,  Helmholtz  and  Baxt^  have  also 
determined  the  speed  of  conduction  in  human  nerves.  They  found  it 
to  be  about  34  m.  in  a  second.  In  the  lower  animals,  the  rate  of  con- 
duction varies  considerably  and  even  in  different  nerves  of  the  same 
animal.  Fredericq  and  Vandervelde,^  for  example,  give  the  value  of 
6  to  12  m.  in  a  second  for  the  nerve  of  the  claw  of  the  sea-crab,  and  v. 
Uxkiill,^  the  value  of  0.4  to  1  m.  in  a  second  for  the  nei  ve  of  the  mantle 
of  cephalopods.  In  the  nerve  plexus  of  the  heart  of  Limulus,  Carl- 
son^ found  the  speed  to  be  0.4  m.  in  a  second  and  in  the  pedal  nerve 
of  Limax  1.25  m.  in  a  second.  The  non-medullated  olfactory  nerve  of 
the  pike  conducts  at  the  rate  of  0.6  to  0.9  m.  in  a  second.^  According 
to  Chauveau,^  the  vagus  fibers  innervating  the  smooth  musculature  of 
the  esophagus  of  mammals,  conduct  with  a  velocity  of  8.2  m.  in  a 
second  and  those  innervating  the  striated  musculature  of  the  larynx, 
at  the  rate  of  66.7  m.  in  a  second.  The  non-medullated  fibers,  there- 
fore, conduct  less  rapidly  than  the  medullated;  moreover,  conduction 
through  the  central  nervous  system  is  effected  at  a  slower  rate  than 
through  the  peripheral  nerves.  It  must  also  be  evident  that  the 
speed  of  the  wave  of  excitation  in  nerve  is  much  less  than  that  of 
certain  physical  energies.  Thus,  sound  travels  with  a  velocity  of 
332  m.  in  a  second,  whereas  light  attains  a  speed  of  332  miUion  meters 
and  electricity  a  speed  of  464  million  meteis  per  second. 

In  recent  years  additional  light  has  been  thrown  upon  this  topic 
by  the  use  of  the  string  galvanometer.  It  may  be  stated  at  this 
time  that  the  passage  of  the  wave  of  excitation  is  associated  with  an 
electrical  variation  which  may  be  accurately  followed  by  a  quickly 
reacting  galvanometer.  Piper^  employed  the  median  nerve  which  he 
stimulated  either  at  the  elbow  or  in  the  axilla.  The  precise  moment  of 
entrance  of  the  excitation  into  the  distant  muscles  was  indicated  by  a 
string  galvanometer  adjusted  in  such  a  way  that  it  registered  the  initial 
phase  of  the  action  current  in  these  muscles.  Knowing  the  length  of 
the  stretch  of  nerve  intervening  between  the  axilla  and  the  elbow,  and 
also  the  time  elapsing  between  the  moment  of  the  application  of  the 

1  Monatsb.  der  Berliner  Akad.,  1870. 

2  Bull,  de  I'acad.  de  Belgique,  C.  r.,  1875,  91. 

3  Zeitschr.  fiir  Biologie,  xxx,  1894,  550. 
*  Am.  Jour,  of  Physiol.,  xiii,  1905,  217. 

^  Nikolai,  Pfltiger's  Archiv,  Ixxxv,  1901,  65. 

^  Acad.  Scienc,  Ixxxvii,  1878. 

7  Pfliiger's  Archiv,  cxxiv,  1908,  591. 


THE    PHENOMENA    OF    CONDUCTION    IN    NERVE  131 

stimulus  at  cither  ])()iiit  and  (lie  (Icflcclioii  of  Ww.  st''in^,  tlu;  velocity 
of  the  wave  could  easily  be  calculated.  If  ,stiinulat(!d  in  the;  axilla, 
the  deflection  followed  after  an  interval  of  0.00578  second,  and  if 
stimulated  at  the  elbow,  after  0.00442  second.  As  the  distance  be- 
tween these  two  points  amounts  in  most  persons  to  160-170  mm., 
the  wave  must  have  progressed  with  a  velocity  of  from  117  to  125  m. 
in  a  second. 

Factors  Altering  the  Speed  of  Conduction  in  Nerve. — The  funda- 
mental condition  for  conduction  is  the  anatomical  continuity  of  the 
nerve-fibers.  If  this  has  been  broken  in  any  way  whatever,  the  excita- 
tion must  fail  to  reach  the  distant  segment.  An  incomplete  block 
may  be  established  in  various  ways,  for  example,  by  compression,  or 
by  crushing  and  stretching.  Conduction  then  reappears  gradually. 
It  may  also  be  observetl  that  the  sensory  fibers  are  somewhat  less 
resistant  than  the  motor  fibers.  Thus,  if  pressure  is  brought  to  bear 
upon  the  ulnar  nerve  at  the  elbow,  the  region  supplied  by  it  "gO€S  to 
sleep,"  but  while  this  state  is  characterized  by  a  simultaneous  diminu- 
tion of  sensory  and  motor  conduction,  the  former  is  usually  depressed 
in  a  much  greater  measure.  Sensation,  therefore,  may  be  destroyed, 
while  the  motor  impulses  are  still  able  to  pass  through  the  block. 
The  return  of  conduction  following  the  removal  of  the  pressure  is 
usually  associated  with  a  peculiar  pricking  sensation  in  the  region 
supplied  by  this  nerve.  While  no  adequate  explanation  of  this  phe- 
nomenon can  be  given,  it  is  commonly  assigned  to  processes  of  excita- 
tion, i.e.,  to  a  temporary  increase  in  the  irritability  of  the  nerve  tissue 
so  affected.  In  fact,  it  has  been  stated  by  Weber,  Schiff,  and  others 
that  an  increased  excitability  of  the  nerve  is  also  experienced  directly 
after  its  division.  Compression-paralysis  is  usually  ushered  in  by  a 
hyperactivity  of  the  distant  muscles.  It  seems,  however,  that  the 
development  of  this  initial  heightened  irritability  depends  upon  the 
character  of  the  injury  as  well  as  upon  the  quickness  with  which  it  is 
effected. 

Mechanical  influences  are  prone  to  give  rise  to  an  initial  phase  of 
excitation  unless  permitted  to  act  gradually,^  while  chemical  agents 
and  cold  do  not.  The  degree  of  pressure  which  may  be  brought  to 
bear  before  conduction  is  abolished,  has  been  determined  by  Ducc- 
eschi^  and  Bethe.^  The  former  employed  a  thin  silk  thread  which 
was  drawn  around  the  nerve  and  slightly  weighted  at  one  end.  A 
weight  of  a  few  grams  sufficed  to  diminish  the  conduction,  while 
a  reduction  of  the  diameter  of  the  nerve  to  one-third  or  one-fourth 
of  normal  abolished  it  altogether.  Naturally,  a  compression  of  this 
intensity  affects  the  enveloping  sheaths  and  perifibrillar  substance 

In  this  category  belong  the  paralyses  in  the  domain  of  the  recurrent  nerve 
following  aneurisms  of  the  branches  of  the  aorta,  and  the  paralysis  of  the  arm 
muscles  in  consequence  of  the  pressure  of  crutches. 

2  Pfitiger's  Archiv,  Ixxxiii,  1901,  38. 

^Allg.  Anat.  und  Physiol,  des  Nervensystemes,  Leipzig,  1903. 


132  THE    PHYSIOLOGY    OF    NERVE 

long  before  it  actually  causes  an  interruption  of  the  fibrillse  of  the  axis- 
cylinders. 

The  fact  that  temperature  influences  the  speed  of  conduction  has 
already  been  established  by  the  earl}^  experiments  of  Helmholtz.  The 
relationship  between  these  two  factors  is  a  direct  one,  i.e.,  the  higher 
the  temperature,  the  more  rapid  the  conduction,  but  this  rule  is  appli- 
cable only  within  physiological  limits.  In  the  case  of  the  motor  neives 
of  man,  variations  between  30  and  90  m.  per  second  have  been  obtained. 
This  is  also  true  of  the  nerves  of  invertebrates,  those  innervating  the 
claws  of  the  lobster,  showing  a  velocity  of  6  m.  at  10°  C,  and  of  12  m. 
at  20°  C.  The  motor  fibers  of  the  sciatic  nerve  of  the  frog  cease  to 
conduct  at  41-44°  C,  but  may  recover  if  the  temperature  is  again 
lowered.  At  50°  C.  their  conductivity  is  lost  altogether.  It  is  also 
of  some  interest  to  note  that  the  velocity  of  the  nerve  impulse  follows 
the  van't  Hoff  law  for  chemical  reactions,  because,  as  has  been  shown 
by  Snyder,^  a  rise  in  temperature  of  10°  C.  approximately  doul)les  the 
conduction.  This  fact  may  be  employed  as  a  proof  that  conduction 
by  nerve  entails  certain  chemical  changes,  because  most  physical  pro- 
cesses present  for  this  range  of  temperature  a  relationship  of  only  1 :1 
or  a  relationship  barely  above  unity. 

Unusual  changes  in  temperature,  and  especially  those  beyond 
phj^siological  limits,  cannot  be  considered  as  constituting  pure  thermal 
influences,  because  they  are  prone  to  injure  the  nerve  tissue  by  bringing 
about  a  loss  of  water  or  certain  differences  in  its  electrical  tension. 
In  this  category  belongs  the  abolition  of  conduction  in  consequence  of 
cauterization  and  extreme  cooling.  Thus,  the  application  of  ice  to 
the  region  of  the  ulnar  nerve  at  the  elbow  results  at  first  in  sensations 
of  pain  and  finally  in  a  complete  loss  of  sensations. 

A  nerve  may  be  kept  in  a  physiological  condition  by  frequently 
moistening  it  with  normal  saline  solution,  but  its  complete  immersion 
in  this  solution  (0.6  per  cent.)  is  generally  followed  by  phenomena 
of  excitation  which,  however,  do  not  appear  if  Locke's  or  Kinger's 
solution  is  employed  instead.  Overton^  has  shown  that  nerve- 
muscle  preparations  retain  their  functional  qualities  in  the  latter 
even  after  15  to  20  days.  Immersion  in  water  diminishes  the  irrita- 
bility of  nerve.  Moreover,  it  is  a  matter  of  common  observation  that 
its  drying  leads  to  violent  contractions  of  the  muscle  which,  to  begin 
with,  are  clonic  in  character  but  soon  become  tetanic.  Acids  do  not 
irritate  unless  concentrated;^  alkalies,  on  the  other  hand,  stimulate 
even  in  solutions  of  0.8-1.0  per  cent.  According  to  Mathews,^  the 
different  solutions  of  the  sodium  salts  act  as  exciting  agents  only  in 
high  concentrations,  but  some  of  them  also  stimulate  when  isotonic 

1  Am.  Jour,  of  Phj^siol.,  xxii,  1908,  179;  also  see:  Ranitz,  Pfliiger's  Archiv, 
Ixviii,  1907,  601. 

*  Pfluffer's  Archiv,  cv,  1904,  2.56. 

3  Kuhne,  Archiv  fur  Anat.  unci  Physiol.,  1860,  315. 

*  Am.  Jour,  of  Physiol.,  xi,  1904,  455. 


THE    PHENOMENA    OF    CONDUCTION    IN   NERVE  133 

to  nerve  tissue.  Potassium  salts  depress.  The  same  is  true  of  mag- 
nesium sulphate.  Conduction  may  be  temporarily  blocked  by  means 
of  this  salt  and  as  effectively  as  by  the  application  of  ice  or  certain 
narcotics.     As  a  general  anesthetic  this  salt  is  useless  and  dangerous.^ 

The  most  important  agents  influencing  the  activity  of  nerve- 
tissue  belong  to  the  group  of  the  anesthetics.  Ether  and  chloroform 
diminish  the  irritability  and  conductivity,  the  latter  agent  being  a 
more  powerful  depressant  than  the  former.  In  these  cases,  the  con- 
ductivity usually  persists  for  sometime  after  the  excitability  has  been 
thoroughly  abolished.  Alcohol  diminishes  the  conductivity,  but  does 
not  materially  affect  the  irritability.  Carbon  dioxid  diminishes  the 
excitability  and  finally  also  the  conductivity.  Among  the  narcotics 
opium,  cocain,  curarin  and  chloral  hydrate  act  as  depressants.  The 
conductivity  of  nerve  may  also  be  gradually  destroyed  by  depriving  it 
of  oxygen.  This  matter  will  be  more  fully  discussed  later  on.  Lastly, 
the  irritability  and  conductivity  of  nerve  may  also  be  varied  by  the 
galvanic  current.  As  this  effect  is  of  fundamental  importance  in 
formulating  "Pfiuger's  Law"  and  the  "Law  of  Unipolar  Stimulation" 
of  normal  muscle  and  nerve,  it  will  be  more  fully  discussed  later  on. 

The  Nature  of  Conduction. — In  spite  of  the  many  views  which  have 
been  formulated  in  explanation  of  the  cause  of  conduction  by  nerve,  it 
cannot  be  said  at  this  time  that  the  exact  nature  of  this  process  has 
been  fully  established.  Thus,  it  has  been  suggested  that  a  nerve- 
fiber  is  a  tube  containing  a  liquid  or  luminiferous  ether,  which  either 
flows  from  place  to  place  or  oscillates  back  and  forth.  Others, 
again,  have  compared  the  nerve-fiber  to  a  metal  wire  and  the  wave 
of  excitation  to  a  progressive  charge  of  electricity.  Still  others  have 
stated  that  the  excitation  arises  in  consequence  of  an  explosive  chem- 
ical change  which  then  advances  along  the  nerve-fiber.  Without  enter- 
ing into  a  detailed  discussion  of  these  different  views,  it  may  be  said 
that  they  are  based  upon  two  fundamental  conceptions,  attaching  to 
conduction  either  a  purely  physical  or  a  purely  chemical  nature. 

The  adherents  of  the  former  theory  claim  that  the  wave  of  excitation 
or  nerve  impulse  is  a  physical  force  propagated  along  nerve-fibers 
without  the  latter  undergoing  metabolic  changes.  It  has  been  sug- 
gested, on  the  one  hand,  that  it  consists  of  a  delicate  quivering  of  the 
molecular  constituents  of  the  nerve,  and,  on  the  other,  that  it  is  due  to 
a  definite  shear  along  the  colloidal  substance  of  the  axis-cylinder. 
An  analogous  process  is  the  conduction  of  electricity  along  copper 
wires  which  necessitates  no  consumption  of  material.  In  accordance 
with  this  theory,  the  nerve  impulse  consists  solely  of  an  electrical 
wave  which  is  known  to  pass  along  a  nerve  whenever  it  is  activated. 

This  entire  process  may  be  illustrated  very  convincingly  with  the  help  of  the 
so-called  core-conductor,  described  by  Hermann.-  A  thin  platinum  wire  ia 
enclosed  in  a  glass  tube  filled  with  a  solution  of  zinc  sulphate.     In  the  several  pairs 

^  Meltzer  and  Peck,  Jour,  of  the  Am.  Med.  Assoc,  Ixvii,  1916,  1131. 
*Pfiuger's  Archiv,  v,  1872,  264;  also  see:  Matteucci,  Compt.  rend.,  Ivi,  1863,  760. 


134 


THE    PHYSIOLOGY    OF    NERVE 


of  collaterals  are  placed  zinc  electrodes  which  in  turn  are  connected  with  the  wires 
leading  to  a  corresponding  number  of  galvanometers.  Thus,  the  central  wire  is 
made  to  represent  the  axis-cylinder,  and  the  surrounding  zinc  solution  the  less 
conductile  myelin  sheath,  but  it  may  also  be  said  that  the  former  corresponds  to 
one  of  the  fibrilla  comprising  the  axis-cylinder  and  the  latter  to  the  perifibrillar 
substance  investing  it.  If  the  end  of  this  conductor  is  now  stimulated  with  induction 
shocks,  the  galvanometers  along  its  course  will  indicate  the  passage  of  an  electrical 
wave  in  a  direction  away  from  the  point  of  stimulation.  This  model  also  gives  rise 
to  electrotonic  alterations  similar  to  those  encountered  in  normal  nerve. 

In  accordance  with  the  second  theory,  which  assumes  that  the  nerve 
impulse  consists  in  progressive  chemical  changes,  it  is  held  that  con- 
duction necessitates  the  destruction  of  some  of  the  constituents  of  the 
nerve.  If  gun  powder  is  spread  out  upon  a  flat  surface  in  the  form  of  a 
narrow  band  and  a  spark  is  applied  to  it  at  one  end,  an  explosive  chem- 
ical reaction  ensues  during  which  this  material  is  progressively  con- 
sumed. Very  obviously,  conduction  in  nerve  is  not  associated  with 
changes  of  this  intensity,  but  it  can  no  longer  be  doubted  that  nerve 
tissue  undergoes  certain  metabolic  alterations  in  consequence  of  its 


Fig.  77. — Schema  to  Show  the  Action  of  the  Core-model. 
p,  The  polarizing  current;  g'  and  g,  the  galvanometers  showing  the  anelectrotonic 
and  catelectrotonic  currents,  respectively.      {Howell.) 

activity  which  differ  from  those  of  other  tissues  only  in  a  quantitative 
way.  This  point  will  be  proved  with  absolute  certainty  by  the  suc- 
ceeding discussion.  Consequently,  a  nerve  impulse  may  be  regarded 
primarily  as  a  wave  of  chemical  change  which  is  accompanied  by  a 
liberation  of  chemical  energy.  In  addition,  the  ensuing  electro- 
lytic dissociation  also  permits  of  the  generation  of  electrical  energy. 
Under  ordinary  conditions,  the  latter  is  the  only  means  at  our  disposal 
to  recognize  the  nerve  impulse  as  it  sweeps  over  a  nerve.  But  while 
this  phenomenon  may  be  proved  to  possess  a  distinct  chemico-physical 
basis,  its  true  character  has  not  been  established  as  yet.  For  the 
present  it  must  suffice  to  characterize  it  as  a  chemico-physical  disturb- 
ance, the  most  evident  product  of  which  is  an  electrical  change,  com- 
monly called  the  wave  of  negativity. 

The  Liberation  of  Energy  by  Nerve. — In  accordance  with  the 
preceding  statement  it  must  be  evident  that  we  cannot  ascribe  a 
chemico-physical  basis  to  the  nerve  impulse  unless  it  can  be  shown 
that  it  is  actually  accompanied  by  chemical  changes  such  as  ordinarily 
serve  as  indications  of  metabolism  and  fatigue.  We  have  previously 
seen  that  the  contraction  of  muscle  is  associated  with  a  liberation  of 


THE    PHENOMENA    OF    CONDUCTION    IN    NERVE  135 

mechanical  energy,  heat  and  electricity,  but  inasmuch  as  nerve  serves 
merely  as  an  instrument  of  conduction,  it  cannot  be  expected  to  give 
rise  to  considerable  amounts  of  energy.  It  is  a  well-known  fact  that 
there  is  no  mechanical  change  in  the  active  nerve  and  hence,  the  only 
point  for  us  to  dotermiiie  is  whether  it  presents  any  indications  of  the 
evolution  of  heat  or  electricity.  So  far  it  has  not  been  possible  to 
demonstrate  the  occurrence  of  thermic  changes  with  any  degree  of 
certainty.  Rolleston,^  for  example,  employed  a  delicate  bolometer  in- 
dicating differences  in  temperature  of  >5ooo°  C.,  but  no  increase  in 
temperature  could  be  detected.  Negative  results  have  also  been  ob- 
tained by  A.  V.  Hill-  who  made  use  of  very  sensitive  thermoelectric 
elements,  indicating  changes  of  a  hundred  millionth  of  a  degree. 
Cremer,^  on  the  other  hand,  does  not  deny  the  possibility  of  thermo- 
genesis,  but  states  that  the  heat  liberated  by  active  nerve  is  less  than 
the  Joule's  heat  of  the  stimulating  current.     Garten,*  moreover,  be- 


FiG.  78. — Current  of  Injury  in  Nerve. 
The  cross-section  of  the  nerve  is  galvanometrically  negative^  to  its  longitudinal 
surface. 

lieves  it  possible  that  the  nerve  possesses  the  power  of  quickly  absorb- 
ing the  slight  amount  of  heat  developed  in  the  course  of  its  metabolism. 
In  the  face  of  more  recent  observations,  it  can  scarcely  be  denied  that 
nerve  undergoes  metabolic  changes,  and  hence,  in  analogy  with  other 
tissues,  it  may  be  inferred  that  nerve  also  liberates  at  least  a  slight 
amount  of  heat. 

In  contrast  to  these  rather  indefinite  results,  it  has  been  fully 
estabUshed  that  nerve  liberates  electrical  energy.  Thus,  if  the  poles 
of  a  galvanometer  are  connected  with  two  separate  regions  of  an  un- 
injured nerve,  the  needle  remains  perfectly  stationary,  proving  thereby 
that  a  normal  nerve  at  rest  is  isoelectric  or  equipotential.  But  if 
one  of  the  non-polarizable  electrodes  is  now  adjusted  to  the  cross- 
section  of  this  nerve,  a  deflection  of  the  needle  results  at  once  (Fig.  78), 
indicating  thereby  the  existence  of  a  demarcation  current  which  we 
call  the  current  of  injury.^    While  its  strength  equals  only  0.02  volt 

1  Jour,  of  Physiol.,  xi,  1890,  208. 

2  Ibid.,  xliii,  1912,  433. 

'  Miinchener  med.  Wochenschr.,  1895. 
*  Physiol,  der  markl.  Nerven,  Jena,  1903. 

^  Discovered  by  DuBois-Reymond  in  1846  (Arch,  fiir  Anat.  u.  Physiol., 
1867,  417). 


136  THE    PHYSIOLOGY    OF    NERVE 

in  medullatcd  nerves,  it  is  said  to  be  more  intense  in  non-medullated 
nerves.  Moreover,  its  strength  diminisiies  very  rapidly  and  especially 
in  the  nerves  of  warm-blooded  animals,  but  the  previous  difference  in 
potential  may  again  be  established  by  making  a  new  section  next  to 
the  first.  Injured  nerves,  therefore,  behave  in  the  same  manner  as 
injured  or  degenerating  muscle.     In  either  tissue  the  current  flows 


Fig.  79. — Current  of  Action  in  Nerve. 
To  begin  with  the  nerve  shows  the  current  of  injury  indicated  by  the  arrows  (as 
in   Fig.   78).     When  stimulated   at  (S  a  negativity  passes  along  the  nerve  which,   on 
reaching  Pole  A,  causes  a  partial  reversal  of  the  current  of  injury,  indicated  by  the 
needle. 

through  the  galvanometer  from  the  non-injured  to  the  injured  portion, 
and  inside  the  nerve  from  the  injured  to  the  non-injured.  The  latter 
we  call  the  axial  current.  An  interesting  modification  of  this  axial 
current^  has  been  observed  in  nerves  normally  possessing  a  mixed 
direction  of  conduction.  Thus,  it  has  been  found  that  the  two  cross- 
sections  of  a  nerve  are  equipotential  only  in  a  mixed   nerve,   while 


D 


Fig.  80. — Schema  to  indicate  the  procedure  used  to  prove  the  diphasic  character  of 
the  action  current.  The  isoelectric  condition  obtained  to  begin  with  is  destroyed  as  soon 
as  the  wave  of  negativity  arrives  at  lead  A. 

nerves  composed  either  of  afferent  or  efferent  fibers,  present  distinct 
differences  in  potential.  In  an  afferent  nerve,  the  central  cross-sec- 
tion is  galvanometrically  negative  to  the  peripheral,  while  in  an  effer- 
ent one  it  is  positive  to  the  peripheral.  Thus,  excised  segments  of 
nerve  always  exhibit  an  axial  stream  in  a  direction  opposite  to  that 
of  their  normal  conduction,  namely,  descending  in  afferent  nerves  and 
ascending  in  efferent  nerves. 

^  DuBois-Reymond,  Unters.  iiber  tier.  ElektrizitJit,  ii,  252;  also  see:  Weiss, 
Pfliiger's  Archiv,  cviii,   1905,  416. 


THE    PHENOMENA    OF   CONDUCTION    IN    NERVE 


137 


When  stimulatod  and  made  to  conduct ,  nerve  tissue  invariably 
exhibits  a  current  of  action,  the  region  of  the  impulse  being  galvano- 
metrically  negative  to  the  resting  portion  of  the  nerve.  This  may  be 
proved  by  first  deviating  the  needle  of  the  galvanometer  by  a  current 
of  injury  (Fig.  79)  and  then  stimulating  its  distant  end  with  an  induc- 
tion shock  {S).  As  the  wave  of  negativity  reaches  the  plus  pole  (A) 
of  the  current  of  injury,  it  reduces  its  potential  and  causes  a  partial 
reversal  of  the  current  of  injury.  The  needle  of  the  galvanometer  then 
swings  toward  and  beyond  zero.  Immediately,  thereafter,  the  needle 
assumes  its  former  position,  namely  at  a  time  when  the  wave  of  nega- 
tivity has  arrived  at  the  negative  injured  cross-section  of  the  nerve  (B). 
Consequently,  the  current  of  action  in  nerve  is  diphasic. 

The  diphasic  character  of  the  action  current  may  be  shown  most  advanta- 
geously by  placing  both  leads  of  the  galvanometer  upon  the  longitudinal  surface 
of  the  nerve  (Fig.  80).  This  system  is 
isoelectric,  because  both  uninjured  points 
A  and  B  have  the  same  potential.  If  the 
nerve  is  now  excited  at  S  with  a  single  in- 
duction shock,  the  wave  of  negativity  re- 
sulting therefrom,  will  cause  a  deflection 
of  the  needle  when  it  reaches  A,  because  B 
is  still  positive.  A  moment,  thereafter,  a 
reversal  will  take  place,  B  now  being 
negative  and  A  positive. 

In  harmony  with  the  results  obtained 
with  the  help  of  the  rheoscopic  frog  pre- 
paration, the  action  current  of  nerve  may 
also  be  employed  as  a  stimulus  for  a  neigh- 
boring nerve.  If  a  short  segment  of  a 
nerve  (A)  is  placed  next  to  the  nerve  of  a 
nerve-muscle  preparation  (B),  the  stimu- 
lation of  A  invariably  gives  rise  to  a  con- 
traction of  the  muscle.  In  explanation  of 
this  phenomenon  it  must  be  mentioned 
that  the  contraction  of  muscle  B  is  effected  in  an  indirect  maner,  i.e.,  the  stimu- 
lation of  nerve  A  gives  rise  to  an  action  current  which  serves  as  a  stimulus  for 
nerve  B.  The  impulse  set  up  in  nerve  B  then  descends  to  the  muscle  and  causes 
it  to  contract.  It  is  to  be  noted,  therefore,  that  the  impulse  in  nerve  B  is  not 
continuous  with  the  first,  but  is  developed  in  a  manner  similar  to  that  of  an  induced 
current  in  the  secondary  coil  of  an  inductorium.  The  impulse  (action  current) 
traversing  nerve  A,  induces  an  impulse  in  nerve  B. 

Action  currents  may  also  be  detected  in  peripheral  nerves  if  the  corresponding 
area  of  the  cerebral  cortex  is  stimulated.  This  result  is  also  obtained  if  the  corre- 
sponding anterior  root  of  the  spinal  cord  is  used  instead.  Sensory  nerves  are  to 
be  preferred  for  experiments  of  this  kind,  because  the  stimulation  by  means  of  the 
electrical  current  may  then  be  dispensed  with.  Thus,  Kiihne  and  Steiner^  have 
detected  negative  variations  in  the  optic  nerve  whenever  the  retina  was  exposed  to 
light,  while  Steinach^  has  noted  similar  fluctuations  in  the  sciatic  nerve  of  the 
frog  on  stimulation  of  the  tactile  receptors  of  the  foot.  In  the  sensory  nerves  of 
the  lateral  organ  of  fishes  these  currents  have  been  observed  by  Fuchs.'     Records 


Fig.  81. — Schema  to  Show  How  a 
Nerve-muscle  Preparation  (B)  May 
BE  Stimulated  BY  an  Action  Current 
IN  Nerve  A. 


1  Untersuchungen  aus  dem  physiol. 

2  Pfluger's  Archiv,  Ixiii,  1896,  495. 

3  Ibid.,  Ix,  1895,  173. 


Inst,  zu  Heidelberg,  iv,  1881,  64. 


138  THE    PHYSIOLOGY    OF    NERVE 

have  also  been  taken  of  the  negative  variations  in  the  depressor  nerve  on  increasing 
the  blood-pressure  in  the  aorta^  and  of  those  occurring  in  the  vagus  nerve  synchro- 
nously with  the  respiratory  movements.^ 

The  Relation  of  the  Nerve  Impulse  to  the  Wave  of  Negativity 
and  the  Action  Current. — The  preceding  discussion  must  have  satis- 
factorily proven  that  the  wave  of  negativity  and  the  nerve  impulse 
are  practically  synonymous  phenomena,  because  they  advance  with  the 
same  velocity  and  cannot  be  dissociated  by  any  known  means. 

A  nerve  impulse  may  be  generated  by  mechanical,  electrical,  ther- 
mal, photic  and  chemical  means,  and  may  be  the  result  of  either  director 
indirect  (reflex)  stimulation.  If  regarded  as  a  purely  physical  phe- 
nomenon, it  will  be  seen  immediately  that  the  impulse  must  consist 
solely  of  a  wave  of  negativity,  while  if  considered  as  a  chemical  phe- 
nomenon, it  must  be  the  product  of  certain  chemical  changes.  In 
accordance  with  the  second  view,  which  is  the  more  widely  accepted 
at  the  present  time,  the  nerve  impulse  consists  of  a  progressive  chem- 
ical process  entailing  catabolism  and  anabolism.  One  of  the  results 
of  these  changes  is  the  wave  of  negativity  which  thus  assumes  the 
character  of  a  true  current  of  action.  This  relationship  having  been 
established,  the  negative  wave  is  to  be  regarded  as  an  associative  phe- 
nomenon of  the  chemical  changes.  Hence,  the  phenomena  of  conduc- 
tion in  nerve  are  very  similar  to  those  taking  place  in  muscle  whenever 
a  wave  of  contraction  sweeps  over  its  constituent  fibers.  The  evidence 
favoring  this  chemico-physical  explanation  of  the  nerve  impulse,  is 
chiefly  derived  from  the  fact  that  the  conduction  in  nerve  entails 
certain  metabolic  changes,  which  will  be  more  fully  discussed  in  the 
succeeding  paragraphs. 

The  Metabolism  of  Nerve  During  Activity. — In  accordance  with 
the  observation  that  contracting  muscle  yields  lactic  acid,  carbon  di- 
oxid  and  other  fatigue  substances,  efforts  have  repeatedly  been  made 
to  show  that  these  bodies  are  also  formed  in  active  nerves.  Inasmuch 
as  the  functional  capacity  of  nerve  varies  directly  with  the  carbon 
dioxid  content  of  the  air  surrounding  it,  A.  D.  Waller^  assumed  at  an 
early  date  that  this  gas  is  actually  liberated  in  the  course  of  the  activity 
of  this  tissue.  It  has  recently  been  proved  by  Tashiro^  that  this  as- 
sumption is  correct.  By  employing  an  extremely  delicate  indicator 
it  could  be  shown  that  even  the  resting  nerves  of  frogs  produce  a 
measurable  quantity  of  carbon  dioxid,  and  besides,  it  was  found  that 
this  amount  may  be  greatly  increased  by  stimulation.  Positive  evi- 
dence of  nerve  metabolism  has  also  been  furnished  by  Bayer^  and 
Frohlich,*'  because  these  investigators  have  shown  that  oxygen  is  abso- 

1  Tschermak,  Pfluger's  Archiv,  xciii,  1903.  24. 

2 Lewandowsky,  Pfiiiger's  Archiv,  Ixxiii,  1898,  298;  also  see:  Einthoven,  Quart. 
Jour,  of  Exp.  Physiol.,  i,  1908,  243. 

3  Brain,  Ixxvi,  1897,  569,  and  Proc.  R.  Soc,  London,  Ixii,  1897,  80. 
*  Am.  Jour,  of  Physiol.,  xxxii,  1913,  137. 
6  Zeitschr.  fiir  allg.  physiol.,  ii,  1903,  169. 
6  Ibid.,  iii,  1904,  131. 


THE  PHENOMENA  OF  CONDUCTION  IN  NERVE 


139 


c 
njpqlii 


71 


lutely  necessary  for  the  i^ropor  function  of  this  tissue.  These  experi- 
ments consisted  essentially  in  enclosing  the  nerve  of  a  nerve-muscle 
preparation  in  a  small  glass  receptacle  so  that  it  could  easily  be  sub- 
jected to  the  influence  of  an  inert  gas,  such  as  hydrogen  or  nitrogen 
(Fig.  82).  While  the  eiTect  was  never  very  striking,  it  could  never- 
theless be  shown  that  the  irritability  and  conductivity  of  the  nerve 
(N)  decreased  very  markedly  if  kept  in  this  inert  medium  for  a  period 
of  several  hours.  Moreover,  the  subsequent  displacement  of  the  inert 
gas  by  oxygen  was  followed  within  a  few  minutes  by  a 
complete  restoration  of  the  function  of  the  nerve.  This 
proves  that  oxygen  is  one  of  the  prerequisites  of  nerve 
metabolism.  As  far  as  the  production  of  acid  is  con- 
cerned, no  positive  results  have  been  obtained.  In  this 
regard  nerves  differ  very  materially  from  the  gray 
matter  of  the  central  nervous  system,  because  the  latter 
has  been  shown  to  become  decidedly  acid  as  a  result  of 
activity.^ 

The  fact  that  nerve  tissue  undergoes  assimilative 
and  dissimilative  changes,  is  also  betrayed  by  the  high 
value  of  the  temperature  coefficient  of  conduction.  It 
has  previously  been  mentioned  that  the  speed  of  the 
nerve-impulse  is  greatest  in  warm-blooded  animals 
and  that  even  moderate  rises  in  temperature  give  rise 
to  a  much  greater  rapidity  of  conduction.  In  this  re- 
gard nerve-tissue  behaves  in  accordance  with  the  van't 
Hoff  law  for  chemical  reactions.  In  addition,  it  should 
be  mentioned  that  nerve  possesses  a  very  appreciable 
refractory  period  during  which  it  cannot  respond  to 
stimuli.  In  the  case  of  the  sciatic  nerve  of  the  frog 
this  period  amounts  to  0.002  second,  but  may  be  in-  nerve 
creased  by  cold,  asphyxia,  anesthetics  and  narcotics. 
It  appears,  therefore,  that  nerve-tissue  requires  a  cer- 
tain time  for  its  anabolic  changes  and  hence,  if  a  The  latter  is  con 
second  stimulus  is  brought  to  bear  upon  it  before  it  nected  with  Kipp 
has  had  sufficient  time  to  complete  these  processes,  it  The  stimulus  is 
must  necessarily  fail  to  conduct  the  succeeding  impulse,  applied  at  S. 

The  brevity  of  the  refractory  period  of  nerve  sug- 
gests that  its  power  of  assimilation  is  unusually  great,  but  this  is 
rather  to  be  expected,  because  the  conduction  in  nerve  does  not  re- 
quire a  considerable  expenditure  of  energy  so  that  the  compensation 
for  the  preceding  dissimilation  can  easily  be  effected  without  profound 
chemical  changes.  This  deduction  is  in  complete  harmony  with  the 
structural  peculiarities  of  nerve.  Contrary  to  the  gray  matter  of  the 
central  nervous  system,  the  white  matter,  as  well  as  the  peripheral 
nerves,  possesses  a  scanty  and  ill-defined  network  of  blood  capillaries 
and  lymph  channels.     This   implies   that   the   blood   supply  of  this 

1  Funke,  Arch,  fiir  Anat.  und  Phj'sioL,  1859,  835. 


preparation 
drawn  through 
glass      chamber. 


140  THE    PHYSIOLOGY    OF    NERVE 

tissue  is  inconsiderable.  Contrariwise,  however,  it  is  evident  that 
its  storative  quahties  are  excellent,  because  while  the  interruption  of 
its  blood  supply  eventually  leads  to  a  reduction  of  its  irritability  and 
conductivity,  this  depression  is  not  quickly  forthcoming;  in  fact,  the 
nerves  of  the  cold-blooded  animals  may  retain  these  properties  for 
a  surprisingly  long  period  of  time  after  their  excision. 

Fatigue  of  Nerve. — Nerve-tissue  possesses  certain  qualities  which 
fortify  it  against  excessive  dissimilation  and  thus  prevent  it  from 
entering  the  state  of  fatigue  with  the  same  readiness  as  other  tissues. 
The  earlier  experiments  pertaining  to  the  development  of  fatigue  in 
nerve,  were  made  with  nerve-muscle  preparations.  In  all  these  in- 
stances the  contraction  of  the  gastrocnemius  muscle  served  as  the  index 
of  activity.  It  is  a  well-known  fact  that  the  repeated  stimulation  of 
any  musculomotor  nerve  eventually  leads  to  a  cessation  of  the  contrac- 
tions, but  this  result  has  been  proved  to  be  due  to  a  fatigue  of  the  end- 
plates  and  not  to  an  exhaustion  of  the  nerve  itself.  Consequently, 
experiments  of  this  kind  cannot  yield  reliable  results  unless  the  muscle 
is  protected  in  some  way  against  these  impulses,  while  the  nerve  is  not. 
A  block  of  this  kind  may  be  established  quite  easily  with  the  aid  of 
curare.  To  begin  with,  it  must  be  shown  that  each  stimulation  of  the 
nerve  produces  a  contraction  of  the  muscle.  If  a  solution  of  curare  is 
now  applied  to  the  latter,  the  ensuing  paralysis  of  the  motor  plates 
prevents  the  impulses  from  reaching  the  effector^  until  the  action  of 
this  drug  has  again  weakened.  During  the  interim,  therefore,  the 
nerve  may  be  stimulated  without  producing  a  muscular  reaction.  By 
this  means  it  has  been  found  that  nerves  may  be  made  to  conduct 
impulses  for  many  hours  without  becoming  fatigued.  Similar  tests 
have  been  made  with  the  vagus  nerve,  the  inhibition  of  the  heart  being 
prevented  during  these  repeated  stimulations  by  the  administration 
of  atropin.^  As  soon  as  the  action  of  this  drug  weakened  after  many 
hours,  the  stimulations  again  became  effective.  Very  similar  results 
have  been  obtained  by  stimulating  the  chorda  tympani  of  the  sub- 
maxillary gland  after  the  administration  of  atropin.  Secretion  was 
resumed  in  this  instance  as  soon  as  the  action  of  this  drug  diminished 
sufficiently  to  permit  the  impulses  to  break  through.^  It  has  also  been 
shown  that  a  galvanometer  connected  with  a  nerve  indicates  a  wave 
of  negativity  with  every  excitation,  and  even  if  these  stimulations  are 
continued  for  many  hours.  Thus,  Beck^  has  stimulated  the  cervical 
sympathetic  nerve  during  seventeen  hours  without  succeeding  in 
greatly  lessening  the  dilatation  of  the  pupil. 

1  Bernstein,  Pfliiger's  Archiv,  xv,  1877,  289;  Wedenski,  Zentralblatt  der  med. 
Wissensch.,  1884,  and  Bowditch,  Jour,  of  Physiol.,  vi,  1885,  133,  The  effect  of 
curare  may  be  removed  within  a  few  minutes  by  the  salicylate  of  physostigmin. 
(Durig,  Zentralbl.  fur  Physiol.,  xv,  1902,  75.) 

2  Scana,  Arch,  fur  Anat.  u.  Physiol.,  1891,  315. 

^Lambert,  Compt.  rend.,  1894,  511;  also  see:  Mascheck,  Sitzungsber.  d. 
Wiener  Akad.,    xcv,  1887. 

*  Pfluger's  Archiv,  cxxii,  1908,  585. 


THE  PHENOMENA  OF  CONDUCTION  IN  NERVE 


141 


C 


(^ 


ilii|il.MI| 


r 


A     B 


These  results  have  led  to  the  early  belief  that  nerve-tissue'  cannot 
be  fatigued  and  tiuit  the  nerve  impulse  is  a  physical  phenomenon. 
It  sliould  be  i'(Mn('ml)ered,  however,  that  these  d(;ductions  have  Ix-en 
based  upon  experiments  which  were  made  in  a  medium  of  air  and  under 
conditions  greatly  favoring  the  activity  of  nerve.  Contrary  to  the 
view  just  expressed,  Bayer  and  Frohlich  have  shown  that  the  refrac- 
tory period  of  nerve  may  be  considerably  lengthened  ])y  means  of 
narcotics  or  by  displacing  the  air  by  an  inert  gas,  such  as  hydrogen  or 
nitrogen.  It  was  also  noticed  that  the  power  of  conduction  of  nerve 
is  markedly  diminished  in  a  medium  of 
this  kind  and  remains  so  until  the  nerve 
has  again  ])een  transferred  into  an  atmos- 
phere containing  oxygen.  Thorncr^  has 
modified  this  experiment  by  placing  the 
nerves  of  two  nerve-muscle  preparations 
in  a  chamber  containing  nitrogen  (Fig. 
83).  One  of  these  nerves  was  then  sub- 
jected to  a  tetanizing  current  centrally 
to  this  chamber  (A).  By  measuring  the 
amplitude  of  the  wave  of  negativity  it 
was  found  that  the  excitability  and  con- 
ductivity decreased  very  rapidly  in  the 
tetanized  nerve,  but  a  similar,  although 
much  slighter,  effect  was  also  detected  in 
the  inactive  nerve  (B).  Further  evidence 
in  favor  of  the  view  that  nerves  may  be 
fatigued,  has  more  recently  been  pre- 
sented by  Garten.  2  While  testing  differ- 
ent non-medullated  nerves,  it  was  noted 
that    the   action  currents  sweeping  over 

the    olfactorius    of    the    pike,    ceased   very      Fig.  83. — Fatigue  op  Nerve. 

shortly  after  the  beginning  of  its  tetaniza-        ^  ^nd  B  two  nerves  placed 

,•  1     Tj  J.  r,        ii        in  glass  chamber.     The   latter  is 

tion  and  did  not  reappear  even  after  the  connected  through  c  with  gas 
electrodes  had  been  applied  to  some  other  generator,  s  points  of  stimuia- 
part  of  this  nerve.     This  fact  tends   to  *^°":   ^'   galvanometers   placed 

,  iii.i        p   1-  I-  •  upon  nerves  to  test  their  irnta- 

show  that   the  latigue  oi  nerve  is  never  biiity. 
restricted  to  the  segment  stimulated  but 

involves  this  structure  in  its  entirety.  Very  similar  results  have 
been  obtained  by  Burian^  in  the  non-medullated  nerves  of  cephalo- 
pods.  This  investigator,  moreover,  has  proved  that  these  symptoms 
of  fatigue  are  not  dependent  upon  electrotonic  alterations  in  the  area 
stimulated.  In  summing  up,  it  may  be  stated  that  the  difficulties 
formerly  encountered  in  proving  fatigue  in  nerve  must  be  assigned 

1  Zeitschr.  fiir  allg.  Physiol.,  viii,  1908,  530. 

2  Beitrage  zur  Physiol,  der  markl.  Nerven,  Jena,  1903;  also  see:  Snowton,  Proc. 
R.  Soc,  ixvi,   1900,  379. 

'  Intern.  Kongress  der  Physiol.,  Heidelberg,  1907. 


142 


THE    PHYSIOLOGY    OF    NERVE 


very  largely  to  the  low  intensity  of  the  metabolism  of  this  tissue  as 
well  as  to  its  remarkable  affinity  for  oxygen.  Nerve-tissue  is  capable 
of  assimilating  this  gas  in  the  briefest  possible  time  from  almost  any 
source.  In  this  regard  nerve  differs  materially  from  the  cell-bodies 
of  the  neurons,  because  the  latter  display  a  very  intense  metabolism 
and  may  therefore  be  more  easily  fatigued. 


CHAPTER  XIII 


THE  REACTION  OF  NORMAL  AND  ABNORMAL  NERVE  AND 

MUSCLE  TO  THE  CONSTANT  AND  INTERRUPTED 

ELECTRICAL  CURRENTS 

Electrotonus. — The  subsequent  discussion  should  prove  of  par- 
ticular value,  because  the  facts  now  to  be  dealt  with  are  absolutely 
essential  for  a  thorough  understanding  of  the  behavior  of  human  nerve 
and  muscle  when  affected  by  degenerative  changes.  If  we  confine  our- 
selves for  the  present  to  the  constant  or  galvanic  current,  it  is  to  be 
noted  that  the  nerve  must  first  be  connected  with  the  battery  by  means 
of  two  non-polarizable  electrodes  which  are  placed  at  a  moderate  dis- 


FiG.  84. — Schema"  to  Show  the  Arrangement  Used  for  the  Stimulation  With 

THE  Descending  or  Ascending  Current. 

£),  descending;  A,  ascending. 

tance  from  one  another.  The  electrode  joined  with  the  positive  pole 
of  the  generator  then  serves  as  the  point  of  entrance  of  the  current 
into  the  nerve,  and  the  one  united  with  the  negative  pole,  as  its  point 
of  exit.  The  former  constitutes  the  anode  (  +  )  and  the  latter  the 
cathode  (  — ).  Provision  must  also  be  made  to  be  able  to  change  the 
potential  of  these  electrodes  at  will.  This  end  is  attained  by  means 
of  a  pole  changer.  In  this  way,  the  anode  may  be  placed  either  near 
to  or  far  away  from  the  central  end  of  the  nerve  (Fig.  84).  If  the 
former,  the  current  must  sweep  over  the  nerve  in  a  direction  from  cen- 
ter to  periphery.     It  is  then  known  as  a  descending  current.     If  the 


THE    REACTION    OF   NORMAL    AND    ABNORMAL    NERVE        143 

latter  adjustment  is  used,  the  current  must  pass  from  the  periphery 
toward  the  cent{>r.     It  is  then  called  an  ascending  current. 

In  the  second  place,  attention  should  be  called  to  the  fact  that  the 
passage  of  a  constant  current  through  a  nerve  gives  rise  to  certain 
chemico-physical  changes  in  the  regions  of  the  anode  and  cathode 
which  have  been  designated  by  DuBois-Reymond  as  electrotonus 
(1843).  This  condition  manifests  itself  in  profound  alterations  in  the 
irritability  and  conductivity  of  the  nerve.  This  change  constitutes 
physiological  electrotomts,  the  one  occurring  in  the  region  of  the  anode 
being  known  as  anelectrotonus  and  the  one  at  the  cathode  as  catelectro- 
tonus.  The  physiological  electrotonus  finds  its  origin  in  the  so-called 
electrotonic  currents  which  arise  in  consequence  of  electrolysis  and 
polarization.     The  latter  may  be  designated  as  physical  electrotonus. 

Nerve  is  a  moist  conductor  and  hence,  it  need  not  surprise  us  to 
find  that  the  passage  of  the  galvanic  current  induces  certain  processes 
of  electrolysis  and  dissociation  which  attain  their  maximal  intensity 
at  the  electrodes,  i.e.,  at  the  points  of  entrance  and  exit  of  the  current. 
Inasmuch  as  the  acid  negative  ions  of  the  electrolytes  are  transferred 
to  the  anode,  this  region  must  assume  an  acid  reaction,  while  the  ac- 
cumulation of  the  basic  positive  ions  upon. the  cathode  must  render 
the  latter  alkaline.  In  the  course  of  time,  this  accumulation  of  nega- 
tive ions  upon  the  anode  and  of  positive  ions  upon  the  cathode  gives 
rise  to  the  so-called  polarization  current,  i.e.,  to  an  electrical  inter- 
change, the  direction  of  which  is  opposite  to  that  of  the  original  polar- 
izing current. 

This  polarization  becomes  most  intense  if  metal  electrodes  are 
employed,  but  the  aforesaid  changes  then  appear  to  be  confined  to  the 
points  of  contact  between  the  metal  and  the  nerve.  If  non-polarizable 
electrodes  are  used,  this  external  form  of  polarization  gives  way  to  the 
internal  form.  Although  still  most  conspicuous  at  the  anode  and 
cathode,  these  changes  are  then  less  closely  restricted  to  the  sur- 
faces of  the  electrodes  and  spread  with  steadily  decreasing  density 
into  the  region  between  these  two  poles  as  well  as  into  those  situated 
immediately  outside  of  them.  The  distance  to  which  they  extend  out- 
side the  poles  depends  upon  the  strength  of  the  primary  galvanic  cur- 
rent. Thus,  electrotonus  may  be  said  to  be  intrapolar  and  extrapolar^ 
in  its  character. 

In  this  connection  emphasis  should  be  placed  upon  the  fact  that 
these  electrotonic  currents  are  absolutely  distinct  from  the  nerve  im- 
pulse, as  well  as  from  the  wave  of  negativity  or  action  current  and  the 
current  of  injury.  Thus,  it  has  been  proven  that  their  velocity  is  much 
greater  than  that  of  the  nerve  impulse  as  betrayed  by  the  speed  of  the 
negative  variation.-  In  the  second  place,  it  has  been  shown  that  they 
may  attain  a  strength  twenty-five  times  greater  than  that  of  the  cur- 
rent of  injury.     Their  distinctiveness  is  also  indicated  by  the  fact  that 

1  Pfliiger,  Unters.  iiber  die  Physiol,  des  Elektrotonus,  Berlin,  1859. 
^  Gildermeister  and  Weis,  Pfliiger's  Archiv,  xciv,  1903,  509. 


144  THE    PHYSIOLOGY    OF    NERVE 

they  persist  during  the  entire  period  during  which  the  galvanic  current 
is  passed  through  the  nerve  and  that  their  direction  may  be  altered 
repeatedly  by  simply  reversing  the  primarj'  current.  Action  currents, 
on  the  other  hand,  always  retain  the  same  direction  and  are  of  momen- 
tary duration.  They  may  also  be  produced  by  mechanical,  thermal 
and  chemical  stimuh,  while  the  electrotonic  currents  cannot  be  gene- 
rated by  these  means.  Another  means  of  differentiation  is  furnished 
by  the  fact  that  the  polarization  currents  are  strongest  in  the  extra- 
polar  regions  and  that  their  intensity  diminishes  with  their  distance 
from  the  poles.  These  statements  imply  that  the  passage  of  a  galvanic 
current  through  nerve  (polarizing  current)  gives  rise  first  of  all  to 
electrotonic  currents  (polarization  current)  which  in  turn  lead  to  the 
production  of  a  nerve  impulse.  The  latter,  therefore,  is  the  result  of 
the  first  two  conditions  and  is  by  no  means  a  part  of  them. 

Electrotonic  Differences  on  the  Making  and  Breaking  of  the  Gal- 
vanic Current. — ^If  the  nerve  of  a  nerve-muscle  preparation  is  stimu- 
lated at  definite  intervals  with  a  constant  cm-rent  of  moderate  strength, 
it  will  be  fotmd  that  the  muscle  reacts  only  on  the  making  and  on  the 
breaking  of  this  current,  but  not  during  the  interim,  in  spite  of  the  fact 
that  the  current  continues  to  traverse  the  nerve.  In  accordance  with 
DuBois-Reymond,  it  may  therefore  be  stated  that  the  stimulating 
agent  is  not  the  absolute  strength  of  the  current,  but  rather  the  abrupt 
change  in  its  intensity  which  it  suffers  when  it  is  made  or  broken.  In 
other  words,  a  stimulus  invariably  fails  to  stimulate  as  long  as  it  re- 
mains constant,  but  becomes  effective  immediately  if  its  striking  force 
is  suddenly  altered.  Secondly,  it  has  been  shown  by  Pfliiger  that 
the  making  of  the  galvanic  current  gives  rise  to  electrotonic  changes  at 
the  two  poles,  and  that  those  at  the  anode  are  very  different  from  those 
at  the  cathode.  The  same  holds  true  of  the  breaking  of  the  current, 
but  naturally,  the  changes  then  occurring,  cannot  justly  be  classified 
as  true  anelectrotonic  and  catelectrotonic  phenomena,  becatise  they  do 
not  arise  during  the  passage  of  the  current,  but  immediately  after 
its  cessation.  Strictly  speaking,  therefore,  they  should  be  character- 
ized as  post-anelectrotonic  and  post-cat.electrotonic. 

These  differences  in  the  functional  condition  of  the  nerve  at  the 
points  of  entrance  and  exit  of  the  constant  current  may  be  briefly 
summarized  as  follows: 

(a)  On  the  making  of  the  current  the  excitability  of  the  ner\-e  is  markedly  in- 
creased at  the  cathode  and  decreased  at  the  anode.  These  changes  are  most 
pronounced  at  the  poles,  but  also  spread  with  gradually  decreasing  intensity  into 
the  intrapolar  and  extrapolar  regions.  Consequently,  an  indifferent  zone  must 
exist  somewhere  between  these  two  poles,  namely  at  the  junction  between  the  area 
of  heightened  cathodal  excitability  and  the  area  of  lessened  anodal  irritability. 

(b)  On  the  break  of  the  current  this  condition  is  reversed,  i.e.,  the  anodal  region 
then  possesses  the  greater  irritability  while  the  cathodal  region  is  depressed.  .\s 
has  been  stated  above,  this  effect  appears  in  reality  after  the  breaking  of  the  cur- 
rent, and  forms  therefore  an  electrotonic  wave  in  the  wake  of  the  galvanic  current. 
Thus,  if  the  terminology  of  post-anelectrotonus  and  post-catelectrotonus  is  adhered 


THE   REACTION    OF   NORMAL   AND    ABNORMAL   NERVE        145 


to,  the  term  anelectrotonus  signifies  a  depression  and  the  term  cateloctro tonus  an 
excitation  occurring  during  the  passage  of  the  constant  current. 

(c)  It  is  also  essential  to  remember  that  the  excitatory  process  developed  at  the 
cathode  is  always  stronger  than  that  developed  at  the  anode. 

It  appears,  therefore,  that  the  wave  of  excitation  constituting  the 
nerve  impulse,  is  developed  at  the  cathode  on  the  make  and  at  the 
anode  on  the  break  of  the  current.  This  inference  may  be  substan- 
tiated with  a  nerve-muscle  preparation  by  simply  recording  making 
and  breaking  contractions  when  the  anode  is  placed  far  away  from  the 
muscle  and  the  cathode  near  to  it.  It  will  then  be  noted  that  the 
latent  period  of  the  making  twitch  is  much  shorter  than  that  of  the 
breaking  twitch.  This  must  necessarily  be  so,  because  in  the  former 
instance  the  nerve  impulse  arises  at  the  cathode  which  is  situated 
in  the  immediate  vicinity  of  the  muscle;  while  in  the  latter  case  it  is 
produced  at  the  anode  which  lies  at  some  distance  away  from  it.     If 


Fig.  85. — Methods  Used  to  Show  Electrotonic  Changes  on  Making  and 
Breaking  of  Galvanic  Current. 
K,  key  for  making  and  breaking  of  current;  P,  pole  changer  for  making  either 
end  of  muscle  (M)  anodic  or  cathodic;  D,  clamp  applied  to  muscle  to  destroy  contraction 
wave  but  not  wave  of  excitation;  W,  weights  attached  to  ends  of  muscle.  These  may 
be  displaced  by  writing  levers. 

the  current  is  now  reversed  so  that  the  anode  comes  to  lie  near  the 
muscle  and  the  cathode  far  away  from  it,  the  latent  period  will  show 
a  greater  length  on  the  making  of  the  current.  On  the  making,  the 
cathode  serves  as  the  stimulus  and  this  pole  is  situated  in  this  case  far 
away  from  the  muscle,  while,  on  breaking,  the  excitation  results  at 
the  anode  which  lies  very  near  the  muscle. 

The  preceding  statement  may  also  be  proved  by  the  procedure  of  Engelmann 
(Fig.  85).  The  positive  and  negative  poles  of  a  battery  are  connected  with  the 
two  ends  of  along  muscle,  such  as  the  sartorius  (3/).  This  muscle  is  then  con- 
stricted about  midpoint  between  its  poles  by  means  of  a  clamp  (D),  the  com- 
pression being  just  sufficient  to  prevent  the  contraction  of  one-half  from  being 
imparted  to  the  other  half  without  actually  hindering  the  passage  of  the  wave  of 

10 


146 


THE    PHYSIOLOGY    OF    NERVE 


excitation.  The  writing  levers  (W),  attached  to  the  two  ends  of  the  muscle,  are 
adjusted  in  the  same  ordinate,  so  that  any  difference  in  the  onset  of  the  contractions 
in  the  two  halves  will  be  indicated  in  the  record.  On  making  the  current  by  closing 
the  key  (k),  the  contraction  invariably  begins  at  that  end  of  the  muscle  which  is 
connected  witl\the  cathode  (C),  while  on  breaking  the  current  the  end  joined  with 
the  anode  (A)  is  activated  first.  The  polarity  of  the  muscle  is  then  changed  by 
reversing  the  bridge  of  the  Pohl  commutator  (P)  interposed  in  the  circuit,  so  that 
the  previously  cathodic  end  now  becomes  anodic.  Although  reversed  as  far  as 
the  muscle  is  concerned,  the  results  will  be  identical  with  the  preceding.  This 
experiment  may  be  modified  in  the  following  manner.     It  is  a  well-known  fact  that 

a  much  more  lasting  character  may  be  im- 
^-^vv(^''i^^{z-)  parted  to  the  contractions  by  the  use  of  a 

^  ^  strong  galvanic  current.     The  one  obtained  on 

^  l-  S  making  the  current  is  designated  as  Wendt's 

tetanus  and  the  one  on  opening,  as  Ritter's 
tetanus.  Engelmann  has  proved  that  these 
tetanic  contractions  remain  confined  to  that 
end  of  the  muscle  in  which  they  originate, 
namely,  the  making  tetanus  to  the  cathodic 
r--  <~,  and  the  opening  tetanus  to  the  anodic  end. 

KJ\ ,        CS       ^r-^  The  phenomenon  of  elcctrotonus  may  also 

^""■■^  be    reproduced  with  the  help  of  the  simple 

core-model  described  in  one  of  the  preceding 
paragraphs,  but  naturally,  the  conditions  here 
met  with  are  purely  physical  in  their  nature 
and  are  not  complicated  by  physiological 
changes,  as  they  are  in  living  nerve.  Thus,  it 
hasbeennoted  that  an  electrolytic  dissociation 
takes  place  between  the  metal  core  and  the 
surrounding  solution  whenever  a  current  is 
passed  through  it.  The  cathodic  ions  are 
made  to  move  toward  the  anode  and  the 
anodic  toward  the  cathode  vmtil  true  electro- 
tonic  currents  have  been  produced. 


Fig.  86. — Method  of  Testing 

THE    ElECTROTONIC    CONDITION     OF 

Nerve. 

K,  key  for  making  and  break- 
ing of  constant  current;  P,  pole 
changer  for  reversing  current  so 
that  either  pole  may  be  made 
anodic  or  cathodic;  S,  point  of 
stimulation  of  nerve  by  means  of 
induction  shocks;  W,  writing  lever 
attached  to  muscle. 


Pfliiger's  Law  of  Contraction. — In 

order  to  show  that  the  passage  of  a 
galvanic  current  gives  rise  to  a  cathodic 
area  of  excitation  and  an  anodic  area 
of  depression,  these  regions  may  be 
stimulated  at  brief  intervals  either 
mechanically  or  by  means  of  single  in- 
duction shocks  (Fig.  86).  In  the  latter 
case,  the  electrodes  (S),  connected  with 
the  secondary  coil  of  an  inductorium,  are  placed  in  the  immediate 
vicinity  of  either  the  positive  or  negative  non-polarizable  electrode. 
By  using  a  strength  of  induction  which,  when  brought  to  bear  upon  the 
cathodic  region,  just  barely  produces  a  contraction  of  the  muscle,  it 
can  easily  be  shown  that  this  same  stimulus  applied  to  the  anodic 
region,  fails  to  incite  a  reaction.  But  even  if  the  same  minimal 
stimulus  is  employed  for  both  regions,  a  comparison  of  the  amplitude 
of  the  contractions  then  resulting  will  show  immediately  that  the  one 
obtained  by  stimulating  at  the  cathode,  is  the  larger  of  the  two.     In 


THE    REACTION    OF   NORMAL   AND    ^VBNORMAL    NERVE        147 

this  connection  reference  should  also  be  niacki  to  the  work  of  Bethe"- 
who  has  shown  that  the  anodic  and  cathodic  rc^^ions  possess  different 
staining  (lualities.  At  the  anode,  the  neurofibrils  of  the  axis-cylinder 
lose  their  power  of  absorbing  methylene-blue,  while  those  situated  at 
the  cathode,  show  an  a])norinally  high  affinity  for  this  dye. 

The  relative  amplitudes  of  the  contractions  ol)tained  by  stimu- 
lating different  points  of  the  anodic  and  cathodic  areas,  have  been 
made  use  of  in  the  construction  of  a  curve  illustrating  the  manner 
in  which  the  excitability  of  nerve  is  changed  during  the  passage  of 
the  galvanic  current.  The  following  schema  of  Pfliiger-  (Fig.  87) 
shows  that  the  subthreshold  anode  and  suprathreshold  cathode  lines 


Fig.  87. — Electrotonic  Alterations  of  Irritability  Caused  by  Weak,  Medium, 
AND  Strong  Battery  Currents. 
A  and  B  indicate  the  points  of  application  of  the  electrodes  to  the  nerve,  A  being 
the  anode,  B  the  cathode.  The  horizontal  line  represents  the  nerve  at  normal  irrita- 
bility; the  curved  lines  illustrate  how  the  irritability  is  altered  at  different  parts  of  the 
nerve  with  currents  of  different  strengths.  Curve  y'^  shows  the  effect  of  a  weak  current, 
the  part  below  the  line  indicating  decreased,  and  that  above  the  line  increased  irrita- 
bility, at  xi  the  curve  crosses  the  line,  this  being  the  indifferent  point  at  which  the 
catelectrotonic  effects  are  compensated  for  by  anelectrotonic  effects;  y''-  gives  the  effect 
of  a  stronger  current,  and  2/\  of  a  still  stronger  current.  As  the  strength  of  the  current 
is  increased  the  effect  becomes  greater  and  extends  farther  into  the  extrapolar  regions. 
In  the  intrapolar  region  the  indifferent  point  is  seen  to  advance  with  increasing  strengths 
of  current  from  the  anode  toward  the  cathode.      (American  Text-hook  of  Physiology.) 

must  vary  in  their  position  with  the  irritability  of  the  nerve  experi- 
mented upon  and  the  strength  of  the  constant  (polarizing)  current. 
This  implies  first  of  all  that  the  polarization,  or  rather,  the  effect  of 
the  polarizing  current  must  increase  with  the  irritability  of  the  nerve, 
and  secondly,  that  the  length  of  nerve  so  affected  must  increase  with 
the  strength  of  the  current.  At  the  point  of  confluency  of  these  anodic 
and  cathodic  fields  in  the  intrapolar  region,  a  conflict  arises  in  conse- 
quence of  which  the  irritability  remains  unchanged.  With  a  weak 
polarizing  current,  this  indifferent  point  lies  near  the  anode,  while  with 
stronger  currents  it  is  shifted  more  and  more  toward  the  cathode. 
This  fact  implies  that  strong  currents  are  more  depressant  than  weak 
currents,  and  hence,  a  point  will  eventually  be  reached  when  the 
depression  also  involves  the  cathode.     The  making  increase  in  excita- 

^  AUg.  Anat.  und  Physiol,  des  Nervensystemes,  Leipzig,  1903. 
^  Unters.  tiber  die  Physiol,  des  Elektrotonus,  Berlin,  1859. 


148 


THE    PHYSIOLOGY    OF    NEEVE 


bility  at  the  cathode  is  then  much  diminished.  Strong  currents, 
therefore,  cause  a  depression  at  both  poles  but  the  cathodic  depression  is 
always  less  than  that  developed  at  the  anode.  Werigo^  expresses  this 
fact  by  saying  that  the  cathodic  depression  is  initiated  by  a  brief 
period  of  excitation.  It  is  to  be  remembered,  however,  that  Fig.  87 
represents  the  conditions  prevailing  during  the  passage  of  the  constant 
current,  when  the  term  anelectrotonus  is  synonymous  with  depres- 
sion and  the  term  catelectrotonuswith  excitation,  and  does  not  portray 
the  conditions  existing  subsequent  to  the  breaking  of  the  current. 
The  post-anelectrotonic  and  post-catelectrotonic  effects  are  the  reverse 
of  those  just  described,  i.e.,  while  strong  currents  cause  a  depression 
at  both  poles,  the  cathodic  region  is  now  more  highly  depressed. 
At  this  time,  the  stimulus  is  derived  from  the  anodic  excitation  still 
remaining. 

These  electrotonic  differences  are  responsible  for  the  occurrence 
of  the  phenomenon  known  as  "secondary  tetanus  of  nerve."  If  a 
long  piece  of  the  sciatic  nerve  of  a  frog  (^4)  is  placed  beside  the  nerve 
of  a  nerve-muscle  preparation  {B),  as  is  indicated  in  Fig.  81,  the 
excitation  of  the  central  end  of  nerve  {A)  with  a  constant  current 
invariably  results  in  a  contraction  of  the  muscle.  By  making  and 
breaking  the  current  more  rapidly,  the  muscle  may  be  thrown  into 
a  complete  state  of  tetanus.  In  this  case,  it  is  the  electrotonic  current 
in  nerve  {A)  which  produces  the  nerve  impulse  in  {B)  and  the  subsequent 
muscular  reaction.  It  will  be  remembered  from  the  previous  discus- 
sion that  this  result  may  also  be  obtained  with  the  aid  of  an  ordinary 
action  current. 

It  has  been  found  by  Pfliiger  that  the  making  and  breaking  of  a 
weak  galvanic  current  gives  rise  to  a  contraction  only  on  the  make.  In 
this  case,  it  is  immaterial  whether  the  anode  be  situated  near  to  or  far 
away  from  the  muscle,  i.e.,  the  results  are  the  same  whether  the  current 
be  ascending  or  descending.  With  a  medium  current  a  contraction 
is  produced  on  the  make  as  well  as  on  the  break,  and  this  holds  true 
for  the  ascending  as  well  as  for  the  descending  current.  With  a 
strong  current,  the  results  are  more  complex,  because  the  ascending 
current  gives  a  contraction  only  on  the  break,  and  the  descending 
current  only  on  the  make.  These  effects  have  been  formulated  into 
what  is  known  as  Pfltiger's  Law  of  Contraction  which  may  be  summar- 
ized as  follows: 


Current 

Ascending 

Desce 

nding 

Make 

Break 

Make 

Break 

Weak                   

c 
c 

c 

c 

c 
c 

c 

c 

Strong .  .  . 

'  Werigo,  Pfliiger's  Archiv,  Ixxxiv,  1901,  547. 


THE   REACTION    OF    NORMAL    AND    ABNORMAL    NERVE         149 

Clearly,  this  law  is  applicable  only  to  excised  nerve  and  muscle 
when  tested  under  experimental  conditions,  but  its  practical  value 
will  become  apparent  later  on  in  connection  with  the  stimulation  of 
normal  and  degeneratinp;  human  muscle  and  nerve.  Its  explanation 
will  present  no  difficulties  if  the  following  three  fundamental  data  are 
borne  in  mind,  namely: 

(a)  When  a  nerve  is  .stiniulatcd  with  a  jralvauic  current,  an  excitatory  process  is 
set  up  at  the  cathode  on  the  making  and  at  the  anode  on  the  breaking  of  the 
current. 

(b)  The  excitatory  condition  developed  at  the  cathode  on  the  making,  is 
stronger  than  the  one  generated  at  the  anode  on  the  breaking  of  the  current. 

(c)  The  passage  of  a  galvanic  current  through  a  nerve  entails  a  decrease  in  its 
power  of  conduction  which,  although  discernible  at  both  poles,  is  most  strongly 


It      1;  ii      ti 


in 


s 


■*■ 


if       I;  \i      ^ 


Fig.  88. — Diagram  Illustrating  Pfluger's  Law. 
j4.sc,   ascending  current;  Z)esc,   descending  current;   W,   M,   S,  weak,  medium  and 
strong  current.     The  effective  stimulus  is  indicated  in  each  case  by  cross  marks. 

marked  in  the  region  of  the  anode.  Immediately  upon  the  breaking  of  the  current; 
the  anodic  conductivity  returns  to  near  normal,  while  the  cathodic  conductivity  is 
diminished.  With  strong  currents  this  anodic  depression  on  the  making  becomes 
so  powerful  that  it  actually  blocks  the  nerve  impulse  and  thus  prevents  it  from 
reaching  its  destination.  The  same  holds  true  of  the  cathodic  depression  resulting 
after  the  breaking  of  the  strong  constant  current. 

With  a  weak  ascending  or  descending  current,  only  the  two  making 
stimuli  are  effective,  because  in  this  case  the  excitation  which  gives 
rise  to  the  nerve  impulse  is  developed  at  the  cathode  (Fig.  88).  The 
nerve  impulse  resulting  therefrom,  reaches  the  muscle,  because  the 
depression  at  the  anode  on  the  making  of  the  ascending  current  is  not 
sufficiently  intense  to  block  it.  The  same  holds  true  of  the  making 
of  the  descending  current,  and  besides,  the  stimulating  cathode  now 
lies  next  to  the  muscle,  so  that  nothing  can  prevent  the  passage  of 


150  THE    PHYSIOLOGY    OF    NERVE 

the  impulse  into  the  latter.  The  breaking  contractions  are  absent, 
because  both  anodic  stimulations  are  as  yet  too  weak.  As  the  strength 
of  the  current  is  increased  to  medium  (M),  the  l^reaking  contractions 
also  appear,  because  even  the  anodic  stimulations  have  now  attained 
a  strength  sufficient  to  generate  nerve  impulses.  The  making  con- 
tractions, however,  continue  to  be  larger  than  the  breaking,  because 
the  cathodic  stimuli  are  more  powerful  than  the  anodic.  With  medium 
currents  no  direct  ])locking  effects  are  obtained,  although  the  anodic- 
making  and  cathodic-breaking  depressions  are  now  more  powerful 
than  during  the  passage  of  weak  currents. 

With  a  strong  ascending  current  (*S) ,  no  reaction  is  obtained  on  the 
making,  because  the  anode  is  situated  next  to  the  muscle.  The  nerve 
impulse  generated  at  this  time  at  the  cathode  cannot  reach  the  end- 
organ,  because  the  strongly  depressed  and  non-conductile  anodic  region 
intervenes.  On  the  break  of  this  current,  however,  the  impulse  can 
reach  the  motor  organ  without  hindrance,  because  the  now  stimulating 
anode  is  situated  near  the  muscle  and  the  depressed  cathodic  area  far 
away  from  it.  With  a  strong  descending  current  a  contraction  is 
obtained  only  on  the  making,  because  the  stimulating  cathode  is 
now  situated  near  the  muscle  and  the  depressed  anode  far  away  from 
it.  On  the  breaking  of  this  current,  however,  the  impulse  developed 
in  the  anodal  region  cannot  reach  the  muscle,  because  the  non-conduc- 
tile cathode  is  interposed  between  it  and  the  end-organ. 

The  Law  of  Contraction  of  Normal  Human  Nerve  and  Muscle. — 
Pfliiger's  Law  as  such  cannot  be  applied  to  human  muscle  and  nerve, 
because  the  conditions  here  met  with  are  entirely  different  from  those 
presented  by  excised  muscle.  Living  human  muscle  is  covered  by 
skin,  adipose  tissue,  fascia  and  connective-tissue  envelopes,  and  the 
nerves  are  generally  so  deeply  placed  that  they  are  not  accessible  to 
stimulation  by  means  of  two  widely  separated  electrodes.  For  this 
reason,  their  excitation  is  usually  effected  with  a  single  electrode  ad- 
justed as  follows:  The  battery  consists  of  about  25  to  30  cells  which 
may  be  quickly  joined  in  series  so  as  to  be  able  to  increase  the  strength 
of  the  current  with  the  least  possible  loss  in  time.  In  this  circuit  is 
inserted  a  pole  changer  b}^  means  of  which  the  polarity  of  the  elec- 
trodes may  be  reversed  at  any  moment.  One  of  the  electrodes  con- 
sists of  a  broad  metal  plate  wrapped  in  a  bolster  of  cotton.  The  latter 
is  moistened  with  saline  solution  to  reduce  the  resistance  of  the  skin. 
The  other  electrode  is  pointed  and  is  equipped  with  a  key  which  may 
be  closed  and  opened  at  will.  If  a  current  of  a  certain  voltage  is  per- 
mitted to  pass  through  two  electrodes  of  this  construction,  it  will  be 
found  that  the  excitation  invariably  arises  at  the  pointed  one,  because 
the  current  attains  here  its  greatest  density  and  striking  force.  At 
the  broad  metal  plate,  on  the  other  hand,  it  is  able  to  scatter  more 
widely  through  the  tissues  without  actually  acquiring  a  high  stimu- 
lating intensity.  For  this  reason,  the  former  is  designated  as  the 
stimulating  and  the  latter  as  the  indifferent  electrode. 


THE    REACTION    OF    NORMAL    AND    ABNORMAL    NERVE        151 

This  procedure  is  commonly  called  the  unipolar  method  of  stimula- 
tion (Chaveau).  To  begin  with,  the  indifferent  electrode  is  firmly 
applied  to  some  part  of  the  body,  while  the  stimulating  electrode  is 
brought  in  contact  with  the  region  overlying  the  nerve  or  muscle  to 
be  tested.  The  accompanying  Fig.  89  may  serve  to  illustrate  the  ar- 
rangement generally  employed  in  stimulating  the  muscles  of  the  arm. 
But  practically  every  voluntary  muscle  in  our  Ijody  may  be  tested 
in  the  same  way,  although  its  excitation  is  usually  effected  through 
its  motor  nerve  by  applying  the  active  electrode  to  the  region  in  which 
its  nerve  becomes  most  superficial.  The  location  of  these  different 
motor  points  may  be  determined  with  the  help  of  Figs.  90  and  91. 


Fig.  89. — Schema  to  Show  the  Unipolab  Method  of  Stimulation  in  Man. 
The  anode,  +,  is  represented  as  the  stimulating  pole,  applied  over  the  median  nerve. 
The  cathode,  — ,  is  the  indifferent  pole.     (Howell.) 

If  the  stimulating  electrode  is  made  anodic,  it  will  be  found  that 
neither  the  making  nor  the  breaking  of  a  weak  galvanic  current  gives 
rise  to  a  contraction.  If  the  active  electrode  is  now  made  cathodic,  a 
contraction  will  be  obtained  on  the  making  of  this  current.  This  re- 
action is  usually  called  the  cathodic  closing  contraction  (C.C.C.).  On 
repeating  this  procedure  with  a  current  of  medium  strength,  it  will  be 
noted  that  the  anode  also  becomes  effective,  a  contraction  now  resulting 
both  on  the  making  and  breaking  of  this  type  of  current.  These  con- 
tractions are  designated  respectively  as  the  anodic  closing  (A.C.C.) 
and  anodic  opening  contraction  (A.O.C.).     The  cathodic  closure  con- 


152 


THE    PHYSIOLOGY    OF    NERVE 


traction  (C.C.C.)  already  obtained  with  the  weak  current,  is,  of  course, 
retained,  but  no  effect  is  as  yet  in  evidence  on  the  break  with  the 
cathode  presenting.  This  cathodic  opening  contraction  (C.O.C.)  ap- 
pears only  after  the  strength  of  the  current  has  been  materially  in- 
creased by  the  addition  of  several  cells.  Attention  should  also  be 
called  at  this  time  to  the  fact  that  strong  currents  frequently  give  rise 
to  contracture-like  reactions,  which  are  designated  as  galvanotonits. 
As  far  as  human  nerve  and  muscle  are  concerned,  it  will  be  seen,  there- 


M.  flexor  carpi  ol 


M-  flex:  digitor. 
muD,  profuod 


M.  flex,  digit,  subl 
(digit;  indicia  ' 
mioimi) 


M,palmari8brev. 
M,  abductor  digiii 

M.  flexor  digit,  min. 
M.  opponeos  digit. 


M,  lumbricales 


AVrr.  musculocutantut 
U*  bicopK  bracbii 
M.brach  Interna* 


flex.  poll.  brev. 
adductor  poUIa  biOT- 


FiG.  90. — Motor  Points  in  Upper  Extremity.      (Howell.) 

fore,  that  the  gradual  increase  of  the  constant  current  brings  forth 
these  contractions  in  the  order  indicated  in  the  succeeding  table: 

Galvanic  current 


Weak 

Medium 

Strong 

C.C.C. 

C.C.C. 
A.C.C. 
A.O.C. 

C.C.C. 
A.C.C. 
A.O.C. 
C.O.C. 

THE    REACTION    OF    NORMAL   AND    ABNORMAL   NERVE 


153 


In  the  same  manner  as  the  results  obtained  with  excised  muscle 
and  nerve,  have  been  formulated  into  Pfliiger's  law  of  polar  stimulation, 
so  may  the  present  results  upon  human  muscle  and  nerve  be  combined 
into  the  law  of  unipolar  Simulation.  But  inasmuch  as  these  laws  have 
a  different  experimental  basis,  they  cannot  really  be  compared  with 
one  another  unless  this  comparison  be  restricted  to  the  causes  under- 


Alsn'.  ischiadicus 

M.  biceps  fern.  (cap.  long.) 
M.  biceps  fern.  (cap.  brev.) 


N.  pcToneus 
M.  gastrocnem.  (cap.  extern.) 


M.  flexor  ,hallucis  longus 


M.  gluteus  maximus 


M.  adductor  magiius 
M.  seiuitendinosus 
M.  semimembranosus 


N.  tibialis 

M.  gastrocnem.  (cap.  int.) 
M.  soleus 

M.  flexor  digitor.  comm.  longus 
N.  tibialis 


Fig.  91. 


-Nerves   and    Motor  Points  in  Lower   Extremity. 
Peterson.) 


{Church    and 


lying  them.     A  clear  understanding  of  the  second  law  requires  first 
of  all  a  brief  recapitulation  of  the  following  three  fundamental  data : 

(a)  The  making  of  a  galvanic  current  gives  rise  to  an  excitation  at  the  cathode, 
and  its  breaking  to  an  excitation  at  the  anode. 

(6)  The  irritabihty  developed  at  the  cathode  on  the  make  of  the  current,  is 
always  greater  than  that  generated  at  the  anode  on  the  break. 

(c)  The  stimulating  power  of  this  current  is  greatest  in  its  area  of  greatest 
density. 


154 


THE    PHYSIOLOGY    OF    NERVE 


The  effects  of  unipolar  stimulation,  however,  are  complicated  by 
the  fact  that  the  electrodes  cannot  be  applied  directly  to  the  nerve 
but  only  to  the  skin  overlying,  and  hence,  a  number  of  peripolar  re- 
gions invariably  develop  around  the  actual  poles  upon  the  nerve.  If 
the  stimulating  electrode  is  anodic  and  the  indifferent  electrode  ca- 
thodic,  the  various  electrical  lines  enter  the  tissues  as  through  a  nar- 
row gate  and  then  spread  out  fan-like  underneath,  constantly  seeking 
paths  of  least  resistance.  At  the  cathodic  pole,  these  lines  again  con- 
verge and  are  finally  combined  into  a  number  of  smaller  bundles.  At 
every  point  where  these  lines  enter  the  nerve  there  is  established  a 
secondary  anode,  and  wherever  they  emerge,  a  secondary  cathode. 
In  this  way,  a  number  of  secondary  or  physiological  anodes  and  ca- 


FiQ.  92. — Rough  Schema  op  Activb  Threads  of  Current  by  the  Ordinary 

Application  of  Electrodes  to  the  Skin  over  a  Nerve  (Ulnar  Nerve). 

The  inactive  threads  are  given  in  dotted  lines  (after  Erb). 

thodes  are  developed  beneath  the  primary  or  physical  anode  as  well  as 
below  the  physical  cathode.  In  brief,  therefore,  it  may  be  stated  that 
the  results  of  the  stimulation  of  human  muscle  and  nerve  are  depen- 
dent upon  the  interaction  of  these  physical  and  physiological  poles. 

A  fuller  explanation  must  take  into  account  that  the  contraction, 
following  the  making  of  the  current,  is  developed  at  the  physiological 
cathode,  while  the  one  following  the  breaking  of  the  current,  is  devel- 
oped at  the  physiological  anode.  Now,  since  the  stimulating  electrode 
may  be  made  either  anodic  or  cathodic,  and  since  physiological  anodes 
and  cathodes  are  developed  in  either  case,  four  possibilities  arise, 
namely : 

(1)  Anodic  Stimulation : 

(a)  On  making  we  obtain  the  so-called  anodic  closing  contraction  in 
consequence  of  excitatory  changes  resulting  at  the  physiological 
cathode  beneath  the  physical  anode. 


THE    REACTION    OF    NORMAL   AND    ABNORMAL   NERVE        155 

(6)   On  breaking  we  obtain  the  so-called  anodic  opening  contraction  which 
is  due  to  the  excitatory  process  at  the  physiological  anode  beneath  the 
physical  anode. 
(2)   Cathodic  Stimulation: 

(a)  On  making  we  obtain  the  so-called  cathodic  closure  contraction  in 
consequence  of  the  excitation  developed  at  the  physiological  cathode 
beneath  the  physical  cathode. 

(b)  On  breaking  we  olatain  the  so-called  cathodic  opening  contraction 
which  is  caused  by  the  excitatory  alterations  at  the  physiological  anode 
beneath  the  physical  cathode. 

It  has  been  stated  repeatedly  that  the  cathodic  irritabihty  is 
stronger  than  the  anodic.  For  this  reason,  the  two  making  or  closure 
contractions  (C.C.C.  and  A.C.C.)  must  be  stronger  than  the  two  break- 


FiG.  93. — Diagram  Showing  Physical  and  Physiological  Anodes  and  Cathodes. 
A,  the  physical  anode,  or  positive  electrode;   K,  the  physical  cathode,  or  negative 
electrode;  a,  a,  a,  physiological  anodes;    k,  k,  k,  physiological    cathodes.     (American 
Text-book  of  Physiology.) 

ing  or  opening  contractions  (A.O.C.  and  C.O.C).  Thus,  it  only 
remains  for  us  to  see  why  the  cathodic  closure  contraction  precedes 
the  anodic  closure  contraction  and  why  the  anodic  opening  contrac- 
tion appears  before  the  cathodic  opening  contraction.  In  brief, 
this  sequence  of  the  reactions  is  dependent  upon  differences  in  the  den- 
sity of  the  current.  On  making,  the  current  acquires  a  greater  den- 
sity or  striking  force  when  the  physiological  cathode  coincides  with  the 
physical  cathode  than  when  it  lies  in  relation  with  the  physical  anode. 
In  the  first  case,  we  obtain  what  might  be  termed  a  sumn  ation  of 
effects  between  the  inner  physiological  cathode  and  the  outer  physical 
cathode.  The  same  explanation  may  be  given  for  the  fact  that  the 
anodic  opening  contraction  develops  before  the  cathodic  opening 
contraction.  The  excitation  on  breaking  being  developed  at  the 
physiological  anode,  this  stimulation  becomes  more  effective  if  the 
physiological  anode  and  physical  anode  coincide. 

The  Law  of  Contraction  of  Degenerated  Human  Nerve  and  Mus- 
cle.— When  called  upon  to  ascertain  the  functional  condition  of  a 
certain  muscle  and  its  nerve,  use  should  be  made  not  only  of  the  con- 
stant current  but  also  of  the  induced  current.     It  should  be  noted 


156 


THE    PHYSIOLOGY    OF    NERVE 


first  of  all  that  degenerating  muscle  and  nerve  is  very  sensitive  to  the 
galvanic  and  relatively  insensitive  to  the  induced  current,  so  that  even 
a  weak  constant  current  may  produce  an  exaggerated  contraction,  or 
galvanotonus,  while  strong  induction  shocks  may  fail  entirely  in  elicit- 
ing a  response.  This  fact  in  itself  is  suggestive  of  degeneration,  be- 
cause it  indicates  that  the  irritability  of  this  particular  muscle  and 
nerve  has  become  more  nearly  like  that  of  all  sluggishly  reacting  forms 
of  protoplasm.  A  further  means  of  differentiation  is  furnished  by  the 
so-called  law  of  degeneration  which  is  obtained  by  the  same  procedure 
as  the  law  of  unipolar  stimulation,  the  stimulating  electrode  being 
applied  either  to  the  region  of  the  muscle  or  to  that  of  the  nerve  in- 
nervating it  (Erb's  reaction).  For  reasons  not  clearly  understood,  de- 
generated muscle  reacts  first  on  the  making  of  the  galvanic  current 
when  the  anode  is  the  active  electrode,  while,  on  breaking,  the 
cathodic  opening  contraction  is  obtained  before  the  anodic  opening,^ 
In  advanced  cases  of  degeneration,  the  galvanic  excitability  is  also 
diminished,  only  the  first  contractions  remaining  in  evidence  until 
eventually  even  these  disappear.  The  law  of  degeneration  may  be 
tabulated  as  follows: 


Galvanic  current 


Weak 

Medium 

Strong 

A.C.C. 

A.C.C. 
C.C.C. 
C.O.C. 

A.C.C. 
C.C.C. 
C.O.C. 
A.O.C. 

Chilarducci  has  suggested  to  place  the  stimulating  electrode  at 
some  distance  below  the  degenerated  muscle,  because  a  contraction 
may  then  be  elicited  with  currents  three  or  four  times  weaker  than 
those  ordinarily  required  for  indirect  excitation.  Furthermore,  con- 
tractions may  then  be  evoked  long  after  the  direct  stimulation  has 
ceased  to  give  positive  effects.  This  phenomenon,  which  is  called 
"reaction  at  a  distance,  "  may  be  used  for  the  diagnosis  of  degeneration 
of  long  standing  and  unusual  obscurity. 

1  Babinski,  Compt.  rend.,  1899,  343. 


PART  IT 

THE  BLOOD  AND  LYMPH 
IMMUNITY 

SECTION  IV 
THE   BLOOD 


CHAPTER  XIV 
GENERAL  CHARACTERISTICS  OF  THE  BLOOD 

General  Consideration. — The  general  body  fluid  of  the  lowest 
organisms  possesses  the  simplest  possible  composition.  It  is  widely 
distributed  through  the  intercellular  spaces  and  is  separated  from  the 
surrounding  medium  by  a  very  permeable  membrane.  Being  thus 
fully  exposed  to  osmotic  influences  from  without,  different  nutritive 
substances  are  constantly  forced  into  the  organism,  while  its  waste 
products  are  made  to  pass  into  the  medium.  These  osmotic  condi- 
tions, however,  are  adjusted  in  such  a  way  that  the  general  fluid  of 
the  body  is  quite  unable  to  acquire  a  concentration  much  above  that 
of  the  surrounding  medium. 

Separate  circulatory  channels  are  not  present  in  the  lower  forms. 
Instead,  the  alimentary  canal  is  called  upon  to  perform  a  double  func- 
tion, namely,  that  of  serving  as  a  receptacle  in  which  the  nutritive 
substances  undergo  mechanical  and  chemical  reductions,  and  that  of 
distributing  the  assimilated  material  to  the  different  parts  of  the  body. 
A  much  higher  stage  of  development  is  attained  in  those  animals  in 
which  the  alimentary  tract  assumes  a  variegated  shape  and  in  which  its 
different  recesses  eventuall}'  become  disconnected  from  the  main  chan- 
nel to  form  the  beginnings  of  the  circulatory  system.  In  this  manner  a 
number  of  internal  reservoirs  are  developed,  from  the  contents  of  which 
the  tissue-cells  derive  their  nourishment  directly.  But,  while  the 
body-fluid  is  thus  more  thoroughly  protected  against  outside  influences, 
its  isolation  is  not  complete,  because  it  continues  to  be  exposed,  on  the 
one  hand,  to  the  osmotic  power  of  the  contents  of  the  alimentary 
canal  and,  on  the  other,  to  the  conditions  prevailing  in  the  cells  of  the 
tissues. 

With  increasing  cellular  differentiation,  this  fluid  of  the  celom 
gradually  assumes  the  characteristics  of  real  blood.  Moreover,  as  the 
interior  spaces  become  more  variegated,  certain  elementary  forces  are 

157 


158 


THE    BLOOD 


brought  into  play  which  cause  the  fluid  to  move  in  such  a  manner  that 
dehcate  streams  or  even  oscillatory  currents  are  produced.  The  more 
efficient  protection  against  outside  influences,  which  is  thus  afforded 
the  "blood,"  enables  it  to  maintain  a  much  greater  complexity  with- 
out materially  hindering  the  osmotic  interchanges. 

In  the  higher  animals,  the  blood  assumes  all  the  characteristics 
of  a  tissue,  but  in  order  that  the  cellular  units  of  the  body  may  be 
brought  into  relation  with  their  nutritive  source  in  the  shortest  pos- 
sible tine,  it  is  made  to  move  rapidly  through  a  system  of  intricate 
and  recurrent  tubes,  the  driving  force  being  furnished  by  a  central 
muscular  organ,  the  heart.  Besides,  these  animals  are  equipped  with 
a  fluid  known  as  the  lymph  ^  which  serves  the  purpose  of  a  medium 


/^' 

.  o(o  .  .|TT>v 

t/f-i- 

o  ^f,  .  .\o  .|.Y\ 

\\\:]-i4i^i» 

.»L,^ 

^<:j 

.iLiLiLl 

Fig.  94. — The  Development  of  the  Circulatory  System. 
Osmotic  interchanges  take  place  1,  between  the  medium  and  the  substance  of  the 
cell  through  the  cell  wall;  2,  between  the  contents  of  the  alimentary  canal  {AC)  and  the 
tissue  cells  (B) ;  .■^,  between  the  contents  of  the  alimentary  canal  {AC)  and  its  recesses, 
and  the  tissue  cells  {B  and  C),  and  4,  at  the  same  two  places  after  the  recesses  have 
become  separated  from  the  body  canal. 

for  the  osmotic  interchanges  between  the  blood  and  the  tissues.  Thus, 
as  the  amount  of  blood  present  in  the  body  is  relatively  small  whereas 
its  complexity  is  great,  it  must  be  evident  that  the  lymph  forms  an 
economic  factor  of  greatest  importance,  because  its  copiousness  and 
watery  consistency  enable  it  to  enter  the  smallest  spaces  and  to  come 
in  direct  contact  with  practically  every  cell  of  the  body.  The  cells, 
it  is  commonly  stated,  are  bathed  in  lymph,  while  the  blood  itself 
does  not  actually  touch  them.  This  statement,  however,  is  not  in- 
tended to  imply  that  these  nutritive  fluids  are  quite  independent  of 
one  another.  On  the  contrary,  the  lymph  is  derived  originally  from 
the  blood  in  accordance  with  physico-chemical  laws.  It  is  diluted 
plasma  which,  however,  is  not  lost  to  the  blood,  but  is  again  returned 

^  A  third  circulating  fluid  is  the  chyle,  but  as  this  is  merely  lymph  loaded  with 
the  products  of  digestion,  it  need  not  be  considered  separately.  The  same  holds 
true  of  the  intraocular  fluid  and  of  the  liquor  cerebrospinalis. 


GENERAL    CHARACTERISTICS    OF    THE    BLOOD  159 

to  it.  Outside  the  capillary  wall,  t  ho  lymph  serves  as  the  medium  with 
which  the  tissue  cells  intorchanse  their  material.  This  process  having 
been  completed,  it  then  moves  onward  through  the  special  channels 
constituting  the  lymphatic  system,  until  it  again  reaches  the  venous 
collecting  tubes  of  the  main  circulatory  system.  The  lymph,  so  to 
speak,  plays  the  part  of  a  middle  man  b(!tween  the  blood  and  the  cells. 
The  lymph  is  comparable  to  the  general  body-fluid  of  the  lower 
animals,  while  the  blood  forms  a  much  more  specialized  carrier.  Func- 
tionally, however,  these  media  roust  be  regarded  as  fulfilling  the  same 
purpose,  because  they: 

(a)  Equip  the  cells  of  the  tissues  with  the  material  necessary  for  their  existence, 
and  remove  from  them  the  substances  that  are  of  no  further  use  to  them; 

(6)  provide  the  tissues  with  oxygen  in  a  readily  assimilable  form,  and  relieve 
them  of  carbon  dioxid,  one  of  the  products  of  their  metabolism; 

(c)  help  in  the  equalization  and  regulation  of  the  body-temperature; 

(d)  protect  the  organism  against  microbic  infection  and  toxic  influences  of  differ- 
ent kinds,  and 

(e)  disseminate  the  products  of  the  ductless  glands,  known  as  atacoids. 

The  blood  is  a  thick  and  viscous  fluid,  containing  different  bodies 
and  substances  in  solution  and  suspension.  It  is  composed  of  a  fluid 
part,  commonly  designated  as  plasma,  and  a  relatively  large  amount 
of  solids.  The  latter  embrace  nutritive  particles  of  all  kinds,  as  well 
as  formed  elements,  or  corpuscles,  which  in  turn  are  made  up  of  red 
corpuscles  or  erythrocytes,  white  corpuscles  or  leukocytes,  and  blood 
platelets  or  thrombocytes. 


Blood 


Water Plasma 

'  Nutritive  particles, 
Blood  dust  (hemoconia) 


Solids 


f  red  (erythrocytes) 
Corpuscles  j  white  (leukocytes) 

[  platelets  (thrombocytes) 


Relative  Amount  of  Plasma  and  Corpuscles. — Two  methods  have 
been  devised  for  the  determination  of  the  amount  of  the  corpuscular 
material.  The  direct  method  possesses  the  advantage  of  being  easily 
executed.  The  sample  of  blood  to  be  examined  is  mixed  with  a  definite 
quantity  of  potassium  bichromate  and  is  centrifugalized  ^  until  the 
corpuscular  elements  have  been  forced  to  the  bottom  of  the  receptacle. 
Since  the  glass-tubes  used  in  this  test  are  calibrated,  the  amounts  of 
plasma  and  corpuscles  may  be  read  off  directly.  This  entire  procedure 
requires  no  special  aptitude  nor  complicated  apparatus  and  can  be 
completed  before  coagulation  has  set  in.  It  is  also  possible  to  ascer- 
tain the  corpuscular  content  by  measuring  the  electrical  conductivity 
of  the  serum  and  corpuscles.  This  method  depends  upon  the  fact 
that  the  latter  place  a  considerable  resistance  in  the  path  of  an  elec- 
trical current  which  is  directly  proportional  to  the  thickness  of  the 

1  For  clinical  purposes  a  small  centrifuge,  called  a  hematocrit,  is  commonly 
employed  (Blix  and  Hedin). 


160  THE    BLOOD 

layer  formed  by  them.  The  indirect  method,  suggested  by  Hoppe- 
Seyler,  is  analytical  in  its  nature  and  necessitates  the  following  pro- 
cedures. To  begin  with,  the  total  amount  of  proteins  in  a  definite 
quantity  of  defibrinated  blood  is  determined  and  secondly,  also  the 
total  protein  content  of  the  washed  corpuscles  contained  in  an  equal 
amount  of  the  same  blood.  It  must  be  evident 'that  the  value  ob- 
tained as  a  difference,  corresponds  to  the  amount  of  proteins  contained 
in  the  serum  of  this  sample  of  blood,  and  if  the  quantity  of  proteins 
in  a  special  sample  of  the  same  blood  is  now  ascertained,  the  propor- 
tion of  serum  in  the  blood  as  a  whole  can  readily  be  calculated. 

The  proportion  of  plasma  and  corpuscles  differs  widely  not  only 
in  animals  of  different  species  but  also  in  animals  of  the  same  group. 
As  a  rule,  the  volume  of  the  plasma  is  found  to  be  much  greater  than 
that  of  the  corpuscles,  a  relationship  of  2:1  having  been  observed  at 
times.  The  figures  for  human  blood  vary  between  48  and  54  per 
cent.,  the  average  value  for  the  corpuscles  being  about  50  per  cent, 
by  weight,^  or  35  to  40  per  cent,  by  volume.  In  the  dog,  the  corpus- 
cles constitute  36  per  cent,  and  in  the  horse  34.5  per  cent,  by  weight. 

Color  of  the  Blood. — When  present  in  larger  amounts,  the  blood 
exhibits  a  very  characteristic  color,  varying  between  scarlet  red  and 
purple.  Blood  free  from  oxygen  is  dichroitic,  dark  red  in  reflected 
light  and  green  in  transmitted  light.  The  color  impression,  actually 
derived  from  it,  is  in  accord  with  the  amounts  of  oxygen  and  carbon 
dioxid,  or,  more  correctly  speaking,  with  the  amounts  of  oxyhemo- 
globin and  reduced  hemoglobin  present  therein. 

The  blood,  or  rather,  the  body-fluid,  of  the  lower  forms  embraces 
pigments  of  different  color.  Red,  violet,  brown,  green,  and  blue 
blood  has  been  found.  Furthermore,  the  pigment  is  not  always  held 
in  the  corpuscular  elements,  but  may  also  occur  free  in  suspension 
in  the  plasma.  The  earthworm,  for  example,  possesses  colorless 
corpuscles,  while  the  blood-pigment,  called  hemerythrin,  floats  in  the 
plasma.  The  red  coloring  material  in  the  echinoderms  is  known  as 
echinochrome,  while  the  blue  pigment  of  the  molluscs  and  crusta- 
ceans is  called  hemocyamine,  and  the  green  pigment  of  worms, 
chlorocruorine. 

The  plasma  itself  is  a  clear,  amber-colored  liquid  and  does  not  impart 
a  distinct  color  to  the  blood  as  a  whole.  Moreover,  inasmuch  as  the 
leukocytes  and  platelets  are  colorless,  the  only  constituents  to  which  an 
influence  of  this  kind  may  be  attributed,  are  the  red  corpuscles.  It 
should  be  emphasized,  however,  that  single  red  cells  give  solely  a  sen- 
sation of  very  faint  yellow,  and  that  a  distinct  reddish  color  is  obtained 
only  when  many  of  them  are  grouped  together.  The  coloring  matter 
of  the  red  cells  is  the  pigment  of  the  hemoglobin. 

On  entering  the  lungs,  the  blood  exhibits  a  dark  red  color,  while 
that  leaving  them  is  much  lighter.     Obviously,  therefore,  its  passage 

1  Arronet,  Maly's  Jahresber. ;  xvii;  Schneider,  Zentralblatt  fiir  Phvsiol.,  v, 
1891,  362;  and  Stewart,  Jour,  of  Physiol.,  xxiv,  1899,  356. 


GENERAL    CHARACTERISTICS    OF   THE   BLOOD  161 

through  the  capillaries  of  this  organ  has  enabled  it  to  undergo  a 
chemical  change,  which,  as  will  become  (ivident  later,  consists  in  an 
absorption  of  oxj'gen  and  a  loss  of  carbon  dioxid.  As  far  as  the  color- 
ing substance,  hemoglobin,  is  concerned,  its  sojourn  in  the  lungs  ha^ 
permitted  it  to  acquire  a  certain  amount  of  oxygen  in  place  of  that 
which  has  previously  been  turned  over  to  the  tissues.  For  this  reason, 
the  color  of  the  blood  may  be  employed  as  in  index  betraying  the  ex- 
tent of  the  molecular  union  which  has  been  effected  between  the  hemo- 
globin and  the  oxygen  of  the  respired  air.  In  other  words,  it  betrays 
the  degree  of  aeration  or  oxygenation  of  the  blood. 

This  explanation  also  accounts  for  the  differences  in  the  color  of 
the  blood  in  different  parts  of  the  vascular  system.  The  most  decided 
contrast  is  noted  centrally  in  the  large  arteries  and  veins,  while  periph- 
erally all  intermediary  shades  between  crimson  and  purple  may  be 
observed  in  accordance  with  the  stateof  oxygenation  of  the  blood  in  the 
region  examined.  In  this  connection  mention  should  also  be  made  of 
the  fact  that  glandular  and  muscular  activity  is  always  associated 
with  a  greater  flow  of  blood  through  the  active  organ,  in  consequence 
of  which  its  venous  discharge  often  assumes  a  color  more  like  that  of 
its  arterial  supply.  Thus,  it  may  be  noted  at  times  that  the  blood 
returned  from  the  kidney,  is  much  lighter  than  that  of  the  inferior 
vena  cava  with  which  it  eventually  intermingles.  A  more  copious 
supply  of  arterial  blood  is  required  by  an  organ  or  tissue  when  acti- 
vated, because  it  needs  more  material  for  purposes  of  oxidation. 

The  appearance  of  the  different  exposed  regions  of  the  body,  such 
as  the  lips,  conjunctiva,  nails,  and  mucous  membrane  of  the  mouth, 
is  frequently  employed  as  an  index  of  the  degree  of  aeration  of  the 
blood.  Provided  that  the  capacity  of  the  blood-vessels  of  these  parts 
has  not  been  materially  altered,  a  pink  color  signifies  an  adequate 
supply  of  oxygen,  whereas  a  bluish  hue  suggests  a  poverty  in  oxygen 
and  a  superfluity  in  carbon  dioxid.  A  dark  blue  color  may  readily 
be  imparted  to  the  circulating  arterial  blood  by  temporarilj'  suspending 
the  respiratory  movements,  or  by  permitting  the  animal  to  breathe 
air  charged  with  carbon  dioxid.  Outside  the  body  similar  results  may 
be  obtained  by  removing  the  oxygen  from  the  arterial  blood  by  means 
of  an  air  pump,  or  with  the  help  of  a  reducing  agent.  During  asphyxia 
the  blood  assumes  an  almost  chocolate-brown  color.  This  change  can 
also  be  brought  about  locally  by  obstructing  the  venous  return  in  a 
mechanical  way.  As  the  oxygen  is  graduall}'  abstracted  from  the 
blood,  the  part  experimented  upon  assumes  a  much  darker  appear- 
ance. Marked  alterations  also  follow  the  administration  of  poisonous 
substances.  Thus,  carbon  monoxid  gives  rise  to  a  cherrj^-red  color, 
while  phenylhydrazin  produces  a  dark-brown  appearance.  Quite 
similarly,  venous  blood  may  be  made  to  assume  a  much  lighter  color 
by  instituting  vigorous  respirations,  or*  by  shaking  the  shed  blood 
in  atmospheric  air.  Obviously,  this  change  is  brought  about  by  an 
absorption  of  oxygen. 
11 


162  THE    BLOOD 

Even  in  thin  layers  blood  is  not  transparent,  because  much  of  the 
light  entering  it  is  reflected  from  the  surfaces  of  the  formed  elements. 
Its  opacity,  therefore,  is  caused  chiefly  by  the  red  corpuscles. 

Odor  and  Taste. — Blood  possesses  a  salty  taste  and  a  faint  odor. 
The  latter  is  caused  by  volatile  fatty  acids  held  in  solution,  and  be- 
comes more  distinct  when  concentrated  sulphuric  acid  is  added  to  the 
blood.  While  both  factors  vary  somewhat  even  in  animals  of  the 
same  species,  the  odor  of  blood  is  usually  sufficiently  strong  so  that 
an  animal,  when  wounded,  may  easily  be  followed  by  another  pos- 
sessing a  keen  sense  of  smell. 

The  Temperature. — The  factor  responsible  for  the  temperature  of 
the  blood  is  the  metabolism  of  the  tissues.  The  heat  given  off  by  the 
cells  is  retained  in  full  measure  by  the  blood  as  long 
as  it  traverses  well-protected  channels,  but  is  dissipated 
by  it  as  soon  as  it  reaches  the  more  exposed  parts  of 
the  body.  Thus,  it  is  found  that  the  highest  tempera- 
ture prevails  in  the  intrahepatic  veins  and  the  lowest 
in  the  blood-vessels  of  the  fingers,  nose  and  ears. 
Differences  between  36°  C.  (97.7°  F.)  and  39.7°  C. 
(103°  F.)  have  been  recorded;  a  fair  average  value  for 
the  blood  in  central  channels  is  38°  C.  (100°  F.). 

Specific  Gravity. — Tliis  factor  may  be  determined 

Pycxometer.  ^y  means  of  a  pycnometer.  A  small  flask  of  glass, 
large  enough  to  contain  from  3  to  5  c.c.  of  blood,  is 
weighed  when  empty  and  when  filled  with  distilled  water.  The 
value  so  obtained  is  compared  later  on  with  the  weight  of  this  flask 
when  filled  with  blood.  It  need  scarcely  be  mentioned  that  the 
temperature  must  be  the  same  for  the  two  weighings.  If  the 
amount  of  blood  is  very  small,  short  capillary^  tubes  of  glass  may 
be  employed,  and,  if  large,  flasks  of  a  greater  capacity  than  5  c.c. 
The  larger  pycnometers  are  equipped  with  a  thermometer  as  well  as 
with  an  extra  bulbular  enlargement  for  the  reception  of  that  portion 
of  the  blood  which  is  forced  out  when  the  flask  is  filled.  A  second 
method  consists  in  permitting  a  drop  of  blood  to  fall  into  a  fluid 
of  known  specific  gravity.  Various  mixtures  have  been  advocated  for 
this  purpose,  for  example,  glycerin  and  water,  or  benzol  and  chloro- 
form.^ To  begin  with,  the  specific  gravity  should  be  adjusted  at  about 
1.050.  The  procedure  consists  in  quickly  increasing  or  decreasing  the 
specific  gravity  of  this  medium  by  the  addition  of  a  certain  quantity 
of  one  or  the  other  of  these  liquids,  until  the  individual  droplets  of 
blood  are  held  in  the  central  mass  of  the  mixture.  At  this  moment 
their  densities  ma}^  be  said  to  be  practically  the  same.  It  is  then  only 
necessary  to  determine  the  specific  gravitj^  of  the  mixture  by  means  of 
an  ordinary  h^^drometer  corrected  to  the  mixture  used.  If  a  compara- 
tive study  is  made  with  diffefent  samples  of  blood,  care  must  be  taken 
to  make  the  collections  always  from  the  same  blood-vessel  and  under 
*  Hammershlag,  Zeitschr.  fiir  klin.  Med.,  xx,  1892,  444. 


GENERAL  CHARACTERISTICS  OF  THE  BLOOD        1G3 

as  nearly  identical  conditions  as  possible,  because^  inasmuch  as  the 
internal  friction  of  the  blood  varies  with  the  size  of  the  channel,  its 
content  in  solids  must  necessarily  be  subject  to  fluctuations. 

The  specific  gravity  of  the  blood  varies  considerably.  On  the  one 
hand,  it  is  found  that  the  general  ])ody-fluid  of  the  lower  forms  possesses 
a  density  only  slightly  greater  than  that  of  water,  and,  on  the  other, 
that  the  blood  of  the  higher  animals  represents  a  complex  fluid  of 
relatively  high  concentration.  Obviously,  therefore,  the  specific 
gravity  must  increase  steadily,  the  highest  values  being  present  in  the 
mammals.  It  is  true,  however,  that  the  density  of  the  blood  of  closely 
related  animals  is  subject  to  only  slight  variations,  so  that  a  rather 
definite  grouping  of  animals  in  accordance  with  this  factor  is  made 
possible.  Thus  we  find  that  the  specific  gravity  of  human  blood  ex- 
ceeds that  of  the  blood  of  the  dog  or  cat,  and  that  these  in  turn  surpass 
that  of  the  blood  of  the  rabbit.  The  density  of  turtle's  or  frog's 
blood  is  much  less  than  that  of  the  mammalian  blood.  It  must  be 
emphasized,  however,  that  individual  variations  do  occur,  as  may  be 
gathered  from  the  fact  that  the  specific  gravity  of  human  blood  varies 
between  1.054  and  1.066.  A  fair  average  value  is  1.060.  In  woman 
variations  between  1.054  and  1.061  have  been  noted.  Blood  serum 
shows  values  ranging  between  1.028  and  1.032.  The  red  corpuscles 
possess  a  much  greater  density  (1.090),  a  fact  which  accounts  for  the 
rather  quick  deposition  of  these  bodies  in  blood  to  which  an  anticoagu- 
lating  agent  has  been  added. 

It  is  also  of  interest  to  note  that  the  specific  gravity  of  the  blood 
of  the  fetus  is  usually  higher  than  that  of  the  blood  of  the  mother. 
Values,  such  as  1.066  for  the  former  and  1.054  for  the  latter,  are  not 
unusual.  During  the  first  few  days  after  birth  rapid  fluctuations 
between  1.060  and  1.080  are  the  rule,  which,  in  all  probability,  are 
caused  by  a  more  copious  production  of  tissue-fluid.  During  the  first 
few  months  variations  between  1.053  and  1.059  are  encountered;  a 
fair  average  value  at  this  time  being  1.056.  A  slightly  higher  figure, 
namely  1.058,  is  reached  after  the  second  and  before  the  fourth  year. 
Subsequent  to  the  sixth  year  the  average  value  is  1.061.  This  is  re- 
tained throughout  childhood. 

Similar  fluctuations  have  been  recorded  in  dogs,  cats,  rabbits,  and 
other  animals.  It  may  be  stated,  however,  that  the  average  value 
for  dog's  blood  is  somewhat  lower  (1.055)  than  that  of  the  blood  of 
man,  but  higher  than  that  of  the  blood  of  the  cat  (1.050)  or  rabbit 
(1.045).  On  the  whole,  therefore,  it  is  true  that  the  specific  gravity  in 
a  particular  group  of  animals  displays  a  certain  constancy  and  that  the 
minor  variations  just  alluded  to  are  dependent  in  a  large  measure  upon 
such  influences  as  age,  sex,  exercise,  intake  of  solid  food  and  water,  as 
well  as  loss  of  water  by  perspiration  and  otherwise.^ 

^  The  reader  is  reminded  of  the  fact  that  very  profound  changes  in  the  specific 
gravity  are  frequently  encountered  during  pathological  conditions.  Verj^  low 
values  are  noted  in  anemias,  and  very  high  values  in  diseases  which  are  character- 
ized by  an  increase  in  the  number  of  the  red  blood  cells  (polycythemia). 


164  THE    BLOOD 

Reaction. — The  reaction  of  the  blood  as  a  whole,  as  well  as  that  of 
the  plasma,  differs  with  the  indicator.  The  earlier  determinations, 
which  have  usually  been  made  with  glazed  litmus  paper,  have  given  an 
alkaline  reaction,  while  the  more  recent  determinations,  for  which 
phenolphthalein  has  been  emploj-ed,  have  shown  that  its  reaction  is 
acid.  Its  tendenc}^  in  either  direction,  however,  is  so  slight  that  it  is 
really  of  very  little  importance. 

Physicochemical  researches  have  shown  that  the  acidity  or  alkalinity  of  a  fluid 
is  dependent  upon  its  content  in  hydrogen  ions  (  +  )  and  hydroxyl  ions  (  — ).  This 
impUes  that  acids  are  dissociated  with  a  liberation  of  H  ions,  while  bodies  which 
give  rise  to  OH  ions,  behave  like  alkalies.  In  illustration  of  this  statement  might  be 
mentioned  the  dissociation  of  HCl  into  H  (+)  and  CI  (  — ),  and  the  dissociation  of 
NaOH  into  Na  (  +  )  and  OH  (  — ).  Besides,  the  acidity  or  alkalinity  of  the  aqueous 
solutions  of  these  substances  is  directly  proportional  to  the  number  of  H  ions  or 
OH  ions  contained  therein. 

The  number  of  OH  ions  contained  in  the  blood  and  lymph  has  been  determined 
by  an  electrical  process^  and  has  been  found  to  be  very  small,  and  hence,  as  they  do 
not  exceed  the  H  ions,  the  reaction  cannot  be  decidedly  alkaline,  nor  can  it  be  acid 
for  the  same  reason.  The  number  of  the  H  ions  in  the  blood  remains  very  constant, 
presumably  on  account  of  the  presence  in  the  plasma  of  the  salts  of  carbonic  acid, 
phosphoric  acid  and  protein  which  are  all  very  weak  in  their  action.  When  acid 
is  added  to  the  blood,  it  reacts  with  the  carbonates  and  phosphates.  Carbonic 
acid  and  acid  phosphates  are  produced  which  leave  the  bodj',  in  the  first  case, 
through  the  lungs  and,  in  the  second,  through  the  kidneys.  The  tendency, 
therefore,  is  to  establish  a  faint  degree  of  alkalinity  as  quickly  as  possible. 

Litmus  paper  gives  a  distinct  alkaline  reaction,  because  litmus  acid  which  is  the 
indicator  in  this  particular  case,  unites  with  the  Na  of  the  XaHCOs  present  in  the 
blood,  and  leaves  the  carbon  dioxid  uncombined.  The  subsequent  dissociation  of 
the  Xa  and  litmus  acid  enables  the  litmus  acid  to  generate  the  blue  color.  Phenol- 
phthalein is  not  sufficiently  strong  to  cause  such  a  displacement  of  the  carbon 
dioxid.  For  this  reason,  the  titration  methods  cannot  give  accurate  results 
concerning  the  reaction  of  the  blood,  but  solely  regarding  the  amount  of  alkalies 
available  for  titration. 

In  addition  to  such  neutral  salts  as  sodium  and  potassium  chlorid  and  the 
alkali  salts  of  the  proteins  of  the  corpuscles  and  plasma,  the  blood  also  contains  a 
considerable  quantity  of  sodium  carbonate.  This  substance,  however,  cannot 
give  riseto  a  decided  alkaline  reaction,  because  it  is  continuously  charged  with  the 
carbon  dioxid  of  the  tissues.  In  this  way,  the  sodium  carbonate  is  retained  in  the 
form  of  the  bicarbonate,  during  the  dissociation  of  which  OH  ions  arc  not  formed, 
as  is  evident  from  the  formula:  XaHCOs  =  Xa  and  HCO3. 

Like- other  living  tissues,  blood  is  practically  neutral  in  reaction  and  performs  its 
function  best  when  only  very  faintly  alkaline,  but  naturally,  as  it  serves  as  the 
reservoir  for  the  products  of  metabolism,  large  amounts  of  carbon  dioxid  and  other 
acids  are  constantly  added  to  it.  Lender  normal  conditions,  however,  any  tendency 
on  its  part  toward  an  acid  reaction  is  quickly  counteracted  in  the  manner  indi- 
cated. This  property  of  the  blood  to  neutralize  acids  without  acquiring  an  acid 
reaction  to  litmus,  is  designated  as  its  total  alkalinity. 

Osmotic  Pressure. — As  the  osmotic  pressure  is  the  chief  regulatory 
mechanism  by  means  of  which  the  water  content  of  the  tissues  is 
safeguarded,  it  constitutes  one  of  the  most  important  properties  of  the 
blood.     Obviously,  the  normal  concentration  and  composition  of  the 

1  Hober,  Pfliiger's  Archiv,  Ixxxi,  1900,  522;  P.  Franckel,  ibid.,  xciv,  1903,  601; 
Henderson,  Am.  Jour,  of  Physiol,,  xxi,  1908,  427,  and  Michaelis  and  Davidoff,  Bioch. 
Zeitschrift,  xlvi,  1912,  131. 


GENERAL    CHARACTERISTICS    OF   THE   BLOOD  165 

cells  can  only  ho  retained,  if  water  and  nutritive  materials  are  made  to 
move  into  them,  while  th(>ir  waste-products  are  made  to  enter  the 
lymph  and  blood.  Osmotic  streams  are  produced,  the  intensity  of 
which  is  directly  proportional  to  the  difference  in  the  osmotic  pressures 
between  the  lilood  and  the  tissue-fluid.  As  these  pressures  are  dep<'n- 
dent  in  turn  upon  differences  in  the  concentration  of  the  fluids  just 
mentioned,  it  is  of  greatest  importance  that  these  differences  be 
retained  without  allowing  them  to  become  too  great.  This  condition, 
however,  is  not  attained  without  certain  changes,  because  the  body  is 
the  frequent  recipient  of  large  quantities  of  water  and  salts  and  also 
loses  much  water  and  other  material  through  the  secretions  and 
excretions. 

The  osmotic  pressure  of  the  blood  is  determined  chiefly  by  its  content  in  crystal- 
loids, namely  th(>  inorganic  salts,  sugar,  uroa,  and  other  substances.  The  pro- 
teids,  however,  cannot  bo  said  to  be  without  influence.  The  most  convenient 
method  of  measuring  the  osmotic  pressure  consists  in  a  comparison  of  the  freezing 
point  of  the  blood  with  that  of  water  (value  =  A).  A  0.1  molecular  solution 
depresses  the  freezing  point  of  w^ater  0.186°;  and  hence,  if  the  depression  which  a 
certain  solution  is  capable  of  producing,  amounts  to  0.093°,  its  concentration 
must  be  0.05  molecular.  Again,  as  the  former  possesses  an  osmotic  pressure  of 
2.24  atmospheres  at  zero,  the  latter  must  exert  a  pressure  of  1.12  atmospheres. 
For  ordinary  purposes,  therefore,  the  osmotic  pressure  of  the  blood  may  be  meas- 
ured in  a  simple  manner  by  determining  its  freezing  point  with  an  apparatus  such  as 
has  been  described  by  Bartley.^  The  freezing  point  of  mammalian  blood  is  about 
—0.6°  C,  which  figure  implies  that  its  osmotic  pressure  equals  0.6/1.8.5  X  22.4  =  7.3 
atmospheres.  Under  normal  conditions  only  slight  variations  are  observed,^  the 
values  for  human  blood  ranging  between -0.52  and -0.60,  those  for  the  dog  between 
-0.55  and  -0.64,  and  those  for  the  rabbit  between  -0.55  and  -0.62. 

Curiously  enough,  some  animals  are  well-protected  against  the 
osmotic  pressure  of  the  medium  in  which  they  live.  The  bony  fish, 
for  example,  possess  an  osmotic  pressure  of  their  body  fluids  which, 
in  the  salt  water  fish,  is  lower  than  that  of  the  sea  water  and,  in  the 
fresh  water  fish,  higher  than  that  of  the  fresh  water.  This  protection 
which  must  be  ascribed  to  a  peculiar  impermeability  to  water  of  the 
lining  cells  of  the  gill-plates,  enables  these  animals  to  migrate.  As  a 
typical  example  of  this  kind  might  be  mentioned  the  salmon  which 
enters  the  fresh  water  during  the  spawning  period  without  suffering 
injury. 

Electrical  Conductivity. — This  factor  depends  upon  the  amount  of 
salts  present  in  the  blood,  because  the  passage  of  an  electric  current 
necessitates  the  presence  of  dissociated  ions.  Moreover,  as  the  con- 
centration of  the  blood  varies  only  within  very  narrow  limits,  its  con- 
ductivity must  remain  almost  the  same.  It  should  be  emphasized, 
however,  that  the  corpuscles  do  not  permit  the  current  to  pass  very 
readily,  because  they  tend  to  prevent  the  ions  of  the  salts  carrying  the 

^  Archives  of  Diagnosis,  1913. 

^  Hamburger,  OsmotLscher  Druck  und  Jonenlehre,  Wisbaden,  1902,  456; 
Hober,  Physik.  Chernie  der  Zelle,  1902,  26;  also  see :  Handb.  der  Physik.  Chemie  u. 
Medizin  by  Koranyi  u.  Richter  i,  1907,  338. 


IGG  THE   BLOOD 

electric  charges,  from  escaping  from  the  plasma.  For  this  reason,  the 
conductivity  of  the  blood  must  be  attributed  largely  to  the  plasma. 
This  is  proven  Ijy  the  fact  that  clear  plasma  possesses  a  greater  con- 
ducting power  than  plasma  to  which  corpuscles  have  been  added.  ^ 
Viscosity. — When  a  fluid  traverses  a  straight  tube  of  sufficient 
length,  its  different  constituents  arrange  themselves  eventually  paral- 
lel to  the  long  axis  of  the  tube.  It  is  also  to  be  noted  that  the  fluid 
does  not  advance  as  a  uniform  whole,  but  unevenly,  so  that  its  central 
core  attains  a  very  great  speed,  while  its  more  external  layers  progress 
with  a  velocit}'  which  steadily  decreases  from  within  outward.  For 
this  reason,  the  layer  next  to  the  wall  must  remain  perfectly  stationary 
provided,  of  course,  that  it  moistens  the  internal  surface  of  the  tube. 
In  the  second  place,  it  should  be  noted  that  the  individual  molecules 
of  the  fluid  rub  against  one  another,  because  as  the  elements  in  neigh- 
boring layers  move  at  different  speeds,  some  of  them  must  be  brought 


Fig.  96. — Friction  of  Blood. 
E,  external  friction;  iT,  internal  friction. 

in  contact  with  one  another,  while  others  are  separated  from  one 
another.  Hence,  the  movement  of  a  fluid  is  associated  first  of  all 
with  an  external  friction  arising  between  its  outermost  layer  and  the 
internal  surface  of  the  vessel  wall,  and  secondly,  with  an  internal  or 
intermolecular  friction,  which,  as  the  name  indicates,  results  between 
the  different  bodies  held  in  solution  or  suspension. 

If  several  different  fluids  are  forced  through  a  narrow  tube  under 
a  constant  pressure  and  temperature,  the  quantities  obtained  of  each 
dm-ing  a  given  period  of  time,  varies  considerably.  For  example,  if 
glycerin,  water  and  ether  are  used,  the  quantity  of  ether  collected  is 
much  larger  than  that  of  either  water  or  glycerin.  This  difference  in 
the  readiness  with  which  liquids  are  capable  of  traversing  a  capillary 
tube,  is  ascribed  to  differences  in  their  internal  friction.  Quite  simi- 
larly, if  blood  and  water  are  employed,  the  former  displays  a  much 
slower  movement  than  the  latter.  As  can  readily  be  surmised,  this 
tardiness  is  dependent  upon  its  greater  content  in  solids.  Fluids  are 
commonly  described  as  "thick"  and  "thin,"  and  clearly,  the  thinner  the 
fluid,  the  less  must  be  its  internal  friction.  But,  besides  these  purely 
quantitative  differences,  fluids  also  possess  certain  qualitative 
peculiarities  which  impart  to  them  either  a  "sticky"  or  a  "non-sticky" 
character.     The  latter  kind  of  fluid,  very  naturally,  possesses  a  shghter 

1  G.  N.  Stewart,  C.  Phys.,  xi,  1897,  332. 


GENERAL   CHARACTERISTICS    OF   THE   BLOOD  167 

internal  friction,  or  viscosity.  While  frequently  used  as  a  synonym 
for  the  general  term  of  internal  friction,  the  term  viscosity  should  in 
reality  be  restricted  to  that  tj'pe  of  friction  which  has  its  origin  in  the 
qualitative  peculiarity  of  a  fluid. 

It  has  been  shown  by  Burton-Opitz^  that  the  viscosity  of  the 
blood  differs  greatly  in  different  animals,  but  remains  rather  constant 
in  the  same  group  of  animals.  When  comi)ared  with  distilled  water 
at  37°  C.,2  the  viscosity  of  human  blood  is  found  to  be  5.1  times  greater, 
while  that  of  dog's  blood  is  5.0  times  greater.  The  coefficient  for 
cat's  blood  is  4.1,  for  rabbit's  blood  3.1,  and  for  the  blood  of  the  frog 
and  turtle  2.5.  It  is  evident,  therefore,  that  the  viscosity  increases  with 
the  complexity  of  the  blood,  and  thus,  it  may  also  be  inferred  that  the 
viscous  resistance  of  the  plasma  or  serum  is  very  much  less  than  that 
of  whole  blood.  In  fact,  it  is  possible  to  establish  perfectly  normal 
degrees  of  viscosity  by  simply  adding  definite  numbers  of  washed  red 
cells  to  clear  serum. 

The  fact  that  the  viscosity  of  the  blood  is  subject  to  variations  is 
shown  by  the  observation  that  warm  baths  decrease  it,  whereas  cold 
baths  and  exposure  of  the  body  to  hot  air  increase  it.  It  is  also  les- 
sened by  hemorrhage  and  the  injection  of  small  quantities  of  normal 
saline  solution.  Arterial  blood  is  less  viscous  than  venous  blood;  and 
hence,  if  a  venous  character  is  imparted  to  the  former  either  by  tempo- 
rarily obstructing  the  trachea  or  by  permitting  the  animal  to  inhale 
carbon  dioxid,  its  viscous  resistance  becomes  greater  than  normal.  In 
dyspnea  it  is  increased  and  also  during  ether  and  chloroform  narcosis, 
as  well  as  after  the  administration  of  alcohol.  It  is  diminished  by 
starvation  and  increased  by  feeding,  more  especially  by  the  ingestion 
of  proteid  material.^ 

^  Pfliiger's  Archiv,  Ixxxii,  1900;  cxii,  1906;  and  cxix,  1908;  also  Jour,  of  Physiol., 
xxxii,  1904  and  1905;  Amer.  Jour,  of  Physiol.,  vii,  1902;  and  Jour.  Exp.  Med.,  viii, 
1906. 

^  The  coefficient  of  the  viscosity  for  distilled  water  at  37°  C.  has  been  determined 
by  Poiseuille  (Ann.  de  Chem.  et  de  Phys.,  Paris,  1843,  Sec.  3,  p.  7).  Its  value  is 
4700. 

'  For  clinical  purposes  the  viscosity  of  the  blood  is  determined  with  the  help 
of  a  simple  instrument,  known  as  a  viscosimeter.  An  instrument  of  thi.s  kind  was 
first  devised  by  Burton-Opitz  (1903).  Modifications  have  been  presented  more 
recently  by  Hirsch  and  Beck,  Hess  and  Miinzer,  and  Bloch. 


CHAPTER  XV 


THE  CHEMICAL  COMPOSITION  OF  THE  BLOOD 

The  Composition  of  Whole  Blood.  ^ — It  must  be  admitted  that  it 
is  almost  impossible  at  the  present  time  to  obtain  exact  analytical 
data  regarding  the  composition  of  the  blood  on  account  of  its  tendency 
to  coagulate,  and,  because  its  composition  varies  not  only  in  different 
species,  but  also  in  animals  of  the  same  group.  Besides,  considerable 
divergences  may  be  encountered  in  one  and  the  same  animal,  in  accord- 
ance with  the  location  or  functional  importance  of  the  vessels  from 
which  the  blood  is  withdrawn.  Lastly,  it  is  entirely  probable  that  the 
methods  used  at  the  present  time  are  altogether  too  crude  to  allow 
us  to  detect  its  more  intricate  chemical  peculiarities. 

Under  ordinary  conditions,  human  blood  contains  77  to  82  per  cent,  of  water, 
and  18  to  23  per  cent,  of  solids.  The  latter  include  17.3  to  22.0  per  cent,  of  organic 
and  0.6  to  1.0  per  cent,  of  inorganic  material.  Proteins  and  hemoglobin  form  by 
far  the  largest  amount  of  the  organic  mass;  13  to  15  per  cent,  being  the  value  for 
hemoglobin  alone.  In  the  ox,  sheep,  goat,  and  rabbit  the  hemoglobin  content  is 
lower  than  in  man,  while  in  the  dog,  horse,  cat  and  pig  it  is  equal  to  it.     The 


THE  COMPOSITION  OF  DOG'S  BLOOD 

1000  Parts,  by 

weight,  of  blood 

contain 

1000  Parts,  by 

weight,  of  serum 

contain 

1000  Parts,  by 
weight,  of  corpus- 
cles contain 

Water 

810.050 
189 . 950 
133 . 400 
39.680 
1.090 
1.298 
2.052 
0.631 
0.759 
0.054 
3 .  675 
0.251 
0.641 
0.062 
0.052 
2.935 
0.809 

0.576 

923.980 
76.020 

60.140 
1.820 
0.709 
1.699 
1.051 
1.221 
0.016 
4.263 
0.226 

0.113 
0.040 
4.023 
0.242 

0 .  OSO 

644  260 

Solids 

355.750 

Hemoglobin 

327  520 

Protein 

9.918 

Sugar 

Cholesterin 

Lecithin 

2.155 
2.568 

Fat 

Fatty  acids 

Phosphoric  acid:  as  nuclcm 

Na20 

0.088 
0.110 
2.821 

K2O 

0.289 

Fe203 

1.573 

CaO 

MgO 

0.071 

CI 

1.352 

P2O5 

1.635 

Inorganic : 

P2O5 

1.298 

*  Oppenheimer  Handb.  der,  Biochemie,  Jena,  1909. 
168 


THE    CHEMICAL    COMPOSITION    OF    THE    BLOOD 


169 


accompanyinR  table  shows  the  composition  of  dog's  blood  as  determined   by 
Abdorhaldon.*     In  another  table  are  given  the  values  for  the  blood  of  the  horse. 

THE  COMPOSITION  OF  HORSE'S  BLOOD 


1000  Tarts  of  blood 
contain  by  weight 


1000  Parts  of  serum 
contain  by  weight 


1000  Parts  of  corpusclca 
contain  by  weight 


Water 749.020 

Solids 250.980 

Hemoglobin 16G.900 

Protein 69.700 

Sugar 0.526 

Cholesterin 0.346 

Lecithin 2.913 

Fat 0.611 

Phosphoric  acid  as 

nuclein 0 .  060 

Soda 2.091 

Potash 2.738 

Iron  oxid 0.828 

Lime 0.051 

Magnesia 0.064 

Chlorin 2.785 

Phosphoric  acid  .  .  1 .  120 
Inorganic       phos- 
phoric acid 0 .  806 


Water 902.050 

Solids 97.950 

Protein 84 .  240 

Sugar 1.176 

Cholesterin 0 .  298 

Lecithin 1.720 

Fat 1 .  300 

Phosphoric  acid 

as  nuclein 0 .  020 

Soda 4 .  434 

Potash 0 .  263 

Iron  oxid 

Lime 0.1113 

Magnesia 0.045 

Chlorin 3.726 

Phosphoric  acid.  0 .  240 
Inorganic   phos- 
phoric acid .. .  0.0715 


Water 613.150 

Solids 386 .  840 

Hemoglobin....  315.080 

Protein 56  780 

Sugar 

Cholesterin 0 .  388 

Lecithin 3 .  973 

Fat 

Phosphoric  acid 

as  nuclein ...        0 .  095 

Soda 

Potash 4.935 

Iron  oxid 1 .  563 

Lime 

Magnesia 0.0S09 

Chlorin 1 .  949 

Phosphoric  acid        1.901 
Inorganic  phos- 
phoric acid  . .        1 . 458 


Sodium  chlorid  is  the  chief  salt  of  the  serum.  It  forms  60  per  cent,  of  the  ash, 
while  sodium  carbonate  constitutes  about  30  per  cent,  of  it.  Traces  of  the  chlo- 
rids  and  phosphates  of  potassium,  sodium  and  calcium  are  also  present.  The  chief 
salt  of  the  corpuscles  is  potassium  phosphate,  while  that  of  the  plasma  is  sodium 
chlorid.  In  fact,  it  has  been  stated  that  the  latter  is  entirely  wanting  in  the  cor- 
puscles of  some  animals.  The  potassium  content  of  different  corpuscles  fluctuates 
considerably.  Chlorin  exists  in  all  types  of  blood,  but  in  greater  amounts  in  the 
serum  than  in  the  corpuscles.  lodin  is  found  only  in  the  serum,  while  iron  appears 
principally  in  the  erythrocytes,  but  in  small  quantities  also  in  the  leukocytes. 
Traces  of  manganese,  lithium,  copper,  and  lead  have  also  been  obtained. 

Traces  of  fats,  cholesterin,  lecithin,  dextrose,  urea,  and  other  nitrogenous 
extractives  are  also  present  in  the  serum.  The  fats  in  the  corpuscles  average 
0.6  per  cent.,  but  this  figure  may  be  decreased  or  increased  by  feeding.  Thus,  an 
increase  of  ten  times  the  normal  value  has  been  obtained  by  this  means  in  geese, 
while,  in  diabetic  lipemia,  as  high  a  value  as  18  per  cent,  has  been  found.  The 
fats  circulate  in  the  blood  in  very  fine  subdivision,  the  individual  globules  becom- 
ing so  numerous  at  times  that  a  distinct  oily  or  milky  appearance  is  imparted  to 
the  blood  or  to  the  serum  derived  from  it. 

Cholesterin  and  lecithin  are  found  chiefly  in  the  erythrocytes,  nine-tenths  of 
the  solids  of  these  cells  being  formed  by  hemoglobin  and  one-tenth  by  the  stroma. 
In  addition  to  these  two  substances,  the  stroma  also  embraces  proteins  and  salts. 

The  amount  of  sugar  in  the  blood  varies  between  0.1  and  0.15  per  cent,  and, 
although  somewhat  independent  of  the  character  of  the  food  ingested,  maj'  be 
greatly  increased  by  feeding.     As  has  been  pointed  out  by  Claude  Bernard,^  sugar 


1  Zeitschr.  fiir  Physiol.  Chemie,  xxv,  1898, 
^  Lecons  sur  la  diabete,  Paris,  1877. 


170  THE    BLOOD 

makes  its  appearance  in  the  urine  (glycosuria),  when  present  in  the  blood  in  larger 
amounts  than  0.3  per  cent.'     Sugar  is  not  a  constituent  of  the  corpuscles. 

The  urea  content  of  the  blood  varies  between  0.02  and  0.15  per  cent.  It 
increases  after  the  ingestion  of  meat  and  decreases  during  starvation.^  In  normal 
human  blood,  von  Jaksch,'  found  this  body  in  amounts  of  0.05  to  0.06  per  cent. 
An  augmented  protein  metabolism  or  a  retarded  elimination  of  urea  leads  to  an 
accumulation  of  these  substances  in  the  blood.  Traces  of  ammonia  are  also  present. 
The  quantity  of  lactic  acid  varies  considerably;  as  much  as  0.071  per  cent,  has 
been  found. 

The  Constituents  of  the  Blood  Plasma. — ^The  liquid  which  serves 
as  the  medium  for  the  corpuscles,  may  be  obtained  by  rapid  centrifu- 
galization,  or  by  rendering  the  blood  non-coagulable  and  permitting 
the  formed  elements  to  settle.  The  supernatant  portion  of  the  blood 
may  be  made  to  clot  at  any  time  by  the  addition  of  an  agent  possessing 
the  power  of  inciting  coagulation.  The  clotting  of  the  blood  may  be 
said  to  be  chiefly  dependent  upon  the  plasma,  because  the  latter  con- 
tains all  the  substances  essential  for  this  process. 

The  plasma  is  yellowish  in  color,  alkaline  in  reaction,  and  possesses 
a  specific  gravity  of  about  1.026  to  1.029.  Its  composition  per  1000 
parts  is  as  follows: 

Water 902.90 

Solids 97 .  10 

Proteins : 

Fibrin 4.05 

Other  proteins 78 .  84 

Extractives  (including  fat) 5 .  66 

Inorganic  salts 8 .  55 

Sodium  chlorid  is  most  abundant  in  human  blood  plasma.  It  forms  60  to  90 
per  cent,  of  the  total  mineral  matter.  Schmidt  gives  the  following  table  for  each 
1000  parts  of  plasma : 

Mineral  matter 8 .  550 

Chlorin 3 .  640 

SO, 0.115 

PjOs 0.191 

Potassium 0 .  323 

Sodium 3 .  341 

Calcium  phosphate 0.311 

Magnesium  phosphate 0 .  222 

In  general,  it  may  be  said  that  plasma  contains  10  per  cenk  of 
solids  of  which  8  per  cent,  are  in  the  form  of  proteins.  The  latter  are 
classified  as  fibrinogen,  serum-globulin,  paraglobulin  and  serum- 
albumin.  Albumoses  or  peptones  are  not  present.  Inasmuch  as  the 
plasma  of  coagulating  blood  separates  into  fibrin  and  serum,  the  pro- 
teins contained  therein,  may  be  divided  into  those  apportioned  to  the 
fibrin  and  those  contained  in  the  serum.  Among  the  former  we  have 
fibrinogen,  thrombogen,  and  kinase.     The  serum  embraces  proteins, 

1  E.  L.  Scott,  Am.  Jour,  of  Physiol.,  xxxiv,  1914,  271.     (Literature.) 
*  Schondorff,  Pfluger's  Archiv,  liv,  1893,  and  Ixiii,  1896,  192. 
'  Festschrift  fiir  v.  Leyden,  i,  1901. 


THE    CHEMICAL   COMPOSITION    OF    THE   BLOOD  171 

extractives,  and  salts.     The  first  of  these  embrace  serum-globulin, 
serum-alt )uiniii,  fibrin-ferment  and  nuclcoprott'in. 

Blood  Serum. — The  serum  is  a  sticky  liquid,  the  specific  gravity 
of  which  varies  between  1.027  and  1.032;  its  average  value  is  1.028. 
Toward  litmus  it  exhibits  an  alkaline  reaction  which  is  somewhat 
greater  than  that  of  the  plasma.  Its  color  is  faintly  yellow,  shading 
into  green.  While  clear  under  ordinary  conditions,  it  may  become 
cloudy  or  milky  in  consequence  of  its  admixture  with  varying  amounts 
of  fat.  The  yellowish  coloring  material  ordinarily  present  in  fats,  to 
which  the  appearance  of  the  serum  is  due,  is  generally  called  lutein 
or  lipochrome. 

The  quantity  of  the  cellular  material  ordinarily  found  in  serum,  varies  between 
7.0  and  9.7  per  cent.  The  bulk  of  the  latter  is  formed  by  proteins  in  amounts  of 
5.5  to  8.4  per  cent.  The  average  depression  of  the  freezing  point  of  blood-serum  is 
given  as  A  =  -0.526°,  as  against  that  of  whole  blood  which  is  A  =  -0.537°.  The 
following  analytical  data  pertaining  to  serum  have  been  supplied  by  Abderhalden: 

Water : 913.64 

Solids 86.36 

Protein 72 .  50 

Sugar 1.05 

Cholesterol 1 .  238 

Lecithin 1 .  675 

Fat 0 .  926 

Phosphoric  acid  as  nuclein 0 .  0133 

Soda 4.312 

Potash 0 .  255 

Iron  o.xid 

Lime 0.1194 

Magnesia 0 .  0446 

Chlorin 3 .  69 

Phosphoric  acid 0 .  244 

Inorganic  phosphoric  acid 0.0847 

The  Proteins  of  the  Blood. — Fibrinogen,  the  mother-substance  of 
fibrin,  is  associated  with  serum-globulin  and  serum-albumin  (page  216). 
Serum-globulin  is  also  called  paraglobulin,  serum-casein,  or  fibrino- 
plastic  substance.  Besides  being  present  in  plasma  and  serum,  it  is 
also  found  in  lymph,  transudates  and  exudates,  as  well  as  in  the 
corpuscles  and  several  tissues  of  the  body.  The  probability  is  that 
serum-globuhn  is  not  a  separate  substance,  but  consists  of  several 
protein  bodies.  Their  complete  separation,  however,  has  not  been 
effected  as  yet.  Hammarsten  states  that  its  average  composition  is : 
C  52.71,  H  7.01,  N  1.585,  S  1.11,  O  23.02.  According  to  Schmiede- 
berg,  its  molecular  composition  is:  Cii7Hi82N3oS038+/^H20.  The 
blood  of  different  animals  contains  different  amounts  of  this  substance ; 
for  example,  that  of  the  rabbit  1.78  per  cent.,  that  of  man  3.10  per 
cent.,  and  that  of  the  horse  4.56  per  cent.  Serum  is  said  to  contain  a 
larger  amount  of  this  substance  than  plasma,  the  surplus  being  derived 
from  disintegrated  leukocytes. 

The  globulins  are  usually  obtained  by  half-saturation  of  the  serum 


172  THE    BLOOD 

with  ammonium  sulphate.  They  may  also  be  gotten  by  dialysis  with 
distilled  water.  As  globulin  is  insoluble  in  distilled  water,  it  is  pre- 
cipitated. The  latter  method  yields  a  smaller  quantity  than  the  for- 
mer, and  hence,  two  types  of  globulins  have  really  been  isolated, 
namely  euglobulin,  and  pseudoglobulin.  The  latter  is  the  one  that  is 
thrown  down  during  half-saturation  with  ammonium  sulphate. 

Serum-albumin  is  found  in  plasma,  serum,  lymph,  transudates, 
exudates,  and  other  animal  fluids.  It  remains  in  the  serum  after 
half-saturation  with  ammonium  sulphate,  but  is  precipitated  by  com- 
plete saturation.  It  may  also  be  prepared  in  crystalline  form  by  the 
method  of  Giirber.  From  neutral  or  acid  solutions  it  is  isolated  by 
heating  to  70°-75°  C;  in  fact,  it  has  been  stated  that  three  heat  pre- 
cipitations occur,  namely  one  at  73°,  one  at  77°  and  one  at  84°C. 
This  fact  has  been  thought  to  prove  that  serum-albumin  is  a  mixture 
of  three  proteins.  However  that  may  be,  it  may  be  assumed  for  the 
present  that  two  protein  bodies  enter  into  its  formation.  According 
to  Michel,!  its  composition  is:  C  53:08,  H  7.10,  N  15.93,  S  1.90, 
O  21.96,  and  its  molecular  composition,  as  represented  by  Schmiede- 
berg:^  C78H122N20SO24.  The  amount  of  this  body  ordinarily  found  in 
the  blood  of  the  horse  equals  3.67  per  cent,  and  in  human  blood  4.52 
per  cent. 

Thromhogen,  or  inactive  thrombin,  is  prepared  by  adding  an  excess 
of  alcohol  to  serum.  A  precipitation  of  the  proteins  and  thrombin 
results;  the  latter,  however,  is  not  so  easily  coagulated  by  alcohol 
as  the  proteins. 

The  extractives  embrace  nitrogenous  and  non-nitrogenous  material. 
The  former  consists  of  urea  and  small  quantities  of  uric  acid,  creatin, 
creatinin,  xanthin,  hypoxanthin,  and  amino  acids.  The  latter  com- 
prises fats,  soaps,  cholesterin,  and  sugar. 


CHAPTER  XVI 

THE  RED  BLOOD  CORPUSCLES 
A.  PHYSICAL  CHARACTERISTICS 

Shape,  Size  and  Color. — With  the  exception  of  the  camelidae,  the 
mammalian  red  corpuscle,^  when  placed  flat  upon  the  slide,  possesses 
the  shape  of  a  circular  platelet,  and,  when  turned  on  edge,  that  of  a 

^  Verh.  der  phys.  med.  Gesellsch.  zu  Wurzburg,  xxix.  No.  3. 

*  Archiv  fiir  Exp.  Path,  und  Pharm.,  xxxix,  1897,  1. 

3  The  red  corpuscles  of  the  frog  were  first  observed  by  Swammerdam  in  1658 
and  those  of  the  mammal  by  Malpighi  in  1661.  They  were  first  described  by 
van  Loewenboek  in  1673. 


THE    RED  BLOOD    CORPUSCLES 


173 


dumb-bell.'  Its  thin  central  area  is  surrounded  by  a  thick  marginal 
zone.  When  tiie  latter  is  brought  into  focus,  the  center  appears  dark, 
because  its  focal  point  lies  at  this  time  at  a  lower  level.     When  cir- 


Fia.  97a. — Human  Red  Corpus- 
cle Placed  Flat  and  on  Edge. 


Fig.  977). — Red  Corpuscle  of  Frog 
Placed  Flat  and  on  Edge. 


culating  through  the  vascular  channels,  the  fully  developed  red  cell 
does  not  contain  a  nucleus;  in  fact,  the  loss  of  this  constituent  very 
shortly  after  the  cell  has  entered  the  blood-vessels,  is  generally  con- 


FiG.  98. — Area  of  Capillaries. 
Showing  tubules  of  different  diameter,  some  so  small  that  the  red  cells  cannot  enter 
at  all  and  others  through  which  they  can  only  pass  by  assuming  an  elliptical  outline. 

sidered  as  the  cause  of  the  central  depression.     In  the  camels,  the  red 
corpuscle  presents  an  elliptical  outline,  but  resembles  the  preceding 

1  Weidenreich,  Lewis,  Radasch  and  others  hold  that  the  red  corpuscles  assume 
this  shape  only  in  shed  blood  and  are  cup-shaped  or  bell-shaped  while  circulating. 
This  change  is  said  to  be  caused  by  cooling  and  evaporation.  Jordan,  who  has 
reinvestigated  this  subject  more  recently,  states  that  a  freely  moving  corpuscle 
always  shows  a  central  depression.  (Proc.  Soc.  Exp.  Biol,  and  Med.,  xii,  1915.) 
Viewed  from  the  side,  however,  these  biconcave  discs  give  the  impression  of  shallow 
cups,  because  the  pressure  tends  at  times  to  cause  them  to  bulge  out  centrally. 


174 


THE    BLOOD 


type  in  all  other  particulars.  In  other  vertebrates,^  it  is  ellipticaP 
and  contains  a  very  conspicuous  nucleus.  It  is  soft  and  very  elastic, 
peculiarities  which  enable  it  to  traverse  capillary  channels  of  smaller 
diameter  than  its  own.  In  these  minute  tubules  the  otherwise  circular 
discs  often  assume  a  shape  approximating  the  elliptical. 

The  size  of  the  red  cell  differs  greatly  in  different  animals,  but 
varies  only  very  slightly  in  animals  of  the  same  group.  In  man  it 
measures  7.5^^  in  diameter  (7.1  to  7.8ai)  and  1.6/i  in  thickness.  Its 
volume  equals  0.000,000,072  c.  mm.  Variations  in  size  between  6.5 
and  9.3/i  have  been  noted  even  in  normal  persons.  Elliptical  cor- 
puscles have  been  found  in  a  few  individuals.  The  following  compila- 
tion will  show  that  red  corpuscles  are  in  existence  which  are  either 
very  much  smaller  or  larger  than  the  human.* 


Elliptical  corpuscles 

Lama 7 . 5  X    4 .  2^ 

Pigeon 14.7  X    6.5/x 

Frog 23 . 0  X  16 .  3m 

Triton 29.5  X  19.5m 

Proteus 58.2  X  35.6m 

Amphiuma 77.0  X  58.0m 


Circular  corpuscles 

Musk-deer 2 .  3m 

Goat 4.25m 

Sheep 5 .  Om 

Horse 5 .  5m 

Pig 6.0m 

Cat 6 .  2m 

Rabbit 7.1m 

Dog 7.2m 

Man 7.5m 

Ox 8 .  Om 

Elephant 9 .  4m 

If  observed  under  the  microscope,  a  single  mammalian  red  corpus- 
cle possesses  a  yellowish,  or  even  green- 
ish color,  but  if  many  of  them  are 
grouped  together,  a  distinct  sensation  of 
red  is  obtained.  In  shed  blood,  these 
bodies  frequently  arrange  themselves  in 
the  form  of  rolls,  but  since  these  rouleaux 
formations  are  not  found  in  circulating 
blood,  and  rarely  in  defibrinated  blood, 
it  is  assumed  that  their  surfaces  must 
first  be  rendered  sticky  before  this  ag- 
glutination can  take  place.  The  agent 
which  produces  this  change,  must  be 
derived  from  the  fibrin  or  its  precursor, 
because  the  agglutination  may  be  dimin- 
ished or  prevented  altogether  by  adding  normal  saline  solution,  or 
some  other  non-destructive  medium  to  the  blood. 

1  In  lamprey  eels  the  corpuscles  are  round,  biconcave  and  nucleated. 

^  Not  oval,  because  this  term  implies  that  one  of  the  ends  is  more  pointed 
than  the  other. 

'  1m  (micron)  equals  0.001  mm. 

*  Monassein,  Dissertation,  Berlin,  1872;  and  Schilling — Torgau,  Folia  hema- 
tologica,  i,  1912. 


Fig.  99. — Circular   Red  Cor- 
puscles Drawn  to  Scale. 
M,  musk-deer;  G,  goat ;  P,  pig;  Mi, 
man;  0,  ox;  E,  elephant. 


THE    RED   BLOOD    CORPUSCLES 


175 


Variations  in  Shape. — Although  it  is  claimed  by  Schultze^  that  the 
erythrocytes  of  the  chick  possess  active  motion,  it  seems  that  the  red 
blood  cells  of  the  mammals  remain  perfectly  passive  as  long  as  the 
fluid  in  which  they  are  kept,  retains  its  normal  character.  But 
their  form  may  be  changed  at  any  time  by  varying  the  temperature  or 
the  carbon  dioxid  content  of  the  medium,  or  by  permitting  an  elec- 
trical current  to  pass  through  them.     Most  generally,  they  react  to 


Fig.   100. — Human  Blood-Corpuscles  Arranged  in  Rouleaux.     (Funke.) 

these  changes  by  increasmg  their  volume.  Moreover,  Cavazzani 
has  shown  that  if  blood  is  collected  in  an  isotonic  or  hypotonic  solution 
of  sodium  chlorid  to  which  potassium  ferrocyanid  has  been  added,  the 
red  corpuscles  of  man  and  other  annuals  send  out  delicate  protoplasmic 
processes,  the  rapid  motion  of  which  enables  them  to  move  about 
from  place  to  place.  If  a  drop  of  cocain  hydrochlorid  is  then  added  to 
this  solution,  these  filaments  are  retracted  within  a  few  moments. 


I  %  Ji  H^ 

Fig.   101. — PoiKiLOCYTES. 
1  and  2,  Mulberry  shape;  3,  prickly  pear  shape;  4,  shadow. 

Changes  in  the  size  of  the  red  corpuscles  are  frequently  observed 
in  disease.  Cells  possessing  a  diameter  of  about  Qn  are  found  in 
anemia,  while  cells  with  a  diameter  of  lO^u  and  over  are  encountered  in 
persons  suffering  from  pernicious  anemia,  leukemia,  chlorosis  or  cir- 
rhosis of  the  liver.  The  former  are  known  as  microcytes  and  the  latter 
as  megalocytes  or  macrocytes.     When  both  their  size  and  shape  are 

^  Archiv  flir  mikr.  Anat.,  i,  18. 


176 


THE    BLOOD 


altered,  they  are  designated  as  poikilocytes.  The  latter  usually 
exhibit  pointed  projections,  like  burs,  or  surfaces  beset  with  rounded 
elevations. 

Number  of  the  Red  Blood  Corpuscles. — While  the  method  for  the 
counting  of  the  red  cells,  devised  by  Vierordt^  and  Welker^  has  been 
modified  by  different  authors,  the  principle  involved  in  it  has  remained 
the  same.     The  instrument  most  commonly  used  to-day  is  the  hemo- 


W 


c 


o%oo'ol 


Fig.   102. — Hemocytometer.      (Thoma-Zeiss.) 
A,  pipet;  B,  glass  bead;  C,  counting  chamber  seen  from  side;  D,  counting  chamber 
seen  from  above;  E,  field  as  seen  under  microscope. 


cytometer  of  Thoma-Zeiss.^  It  consists  of  a  pipet  (A),  originally 
devised  by  Potain,  and  a  counting  chamber  (C).  Having  thoroughly 
cleansed  the  skin  upon  the  tip  of  the  finger  or  upon  the  lobule  of  the  ear, 
a  small  wound  is  made  with  a  lanzette  or  needle.  A  portion  of  the 
blood  collected  upon  the  integument  is  then  quickly  drawn  into  the 

1  Arch,  fiir  physiol.  Heilkunde,  xiii,  1854,  259. 

^  Prager  Viertalj.  fiir  prakt.  Heilkunde,  iv,  1854, 

^  See  Abb^:  Sitzungb.  d.  Jenaischen  Gesellsch.  f.  Med.,  1878;  also  see:  Biirker, 
Handworterb.  der  Naturw.,  Jena,  1912;  and  Hayem,  in  Sahli's  Lehrb.  d.  klin. 
Untersuchungsmethoden,    Leipzig,  1909. 


THE    IlED   BLOOD    CORPUSCLES  177 

pipet  until  either  point  0.5  or  1  has  been  reached.  The  end  of  the 
pipet  is  then  dried  with  filter  pap(>r  and  ininiediat(>ly  (hpped  into 
an  isotonic  solution'  which  is  intended  to  dilute  the  blood  previously- 
drawn  in.  The  tube  is  then  filled  to  point  101  above  its  bulbular 
enlargement.  Upon  its  withdrawal  from  the  fluid  it  is  again  dried 
with  filter  paper  and  gently  shaken  until  the  blood  and  the  solution 
have  become  thoroughly  mixed.  The  marks  upon  the  tube  signify  that 
if  the  blood  is  drawn  in  as  far  as  point  1  and  the  diluting  fluid  as  far  as 
point  101,  the  original  sample  of  blood  is  diluted  100  times,  whereas, 
if  the  marks  0.5  and  101  are  used,  a  dilution  of  200  times  is  the  result. 

Having  thoroughly  mixed  the  contents  of  the  pipet,  a  drop  or  two 
are  permitted  to  escape  from  the  tube  without  being  used.  The  next 
droplet,  however,  is  collected  upon  the  stage  of  the  counting  chamber 
(C)  and  in  such  a  manner  that  it  does  not  overflow  into  the  space 
next  to  it.  The  entire  compartment  is  then  closed  by  placing  a  cover- 
glass  over  it.  The  surface  of  the  stage  is  exactly  0.1  mm.  below  the 
lower  surface  of  the  cover-glass.  A  series  of  20  squares  are  engraved 
upon  the  former,  the  sides  of  which  measure  3^^o  ^^-  in  length,  and 
hence,  each  possesses  an  area  of  i^oo  sq.  mm.  and  a  capacity  of 
3^^ 00  X  0.1  =  /^ooo  cu.  mm.  Having  counted  the  number  of  cor- 
puscles in  many  of  these  small  squares,  a  fair  average  value  is 
obtained  from  these  figures.  The  value  so  obtained  is  then  multi- 
plied by  the  degree  of  dilution  and  by  4000. 

It  is  only  natural  to  suppose  that  the  size  and  number  of  the  red 
corpuscles  must  preserve  an  indirect  relationship  to  one  another. 
That  this  is  true,  is  borne  out  by  the  following  table ^  which  should  be 
compared  with  the  one  containing  the  data  pertaining  to  the  size  of 
the  different  red  cells. 

1  Various  preserving  solutions  have  been  recommended,  for  example: 

(a)  Hayem's  fluid: 

Hydrarg.  bichlor 0.5  gram. 

Sodii  sulphat 5.0  grams. 

Sodii  chlorid 2.0  grams. 

Aq.  distill 200 . 0  c.c. 

(6)  Gower's  fluid: 

•  Sodii.  sulphat.  gm lOi .  0 

Acid  acetic 3i 

Aq.    destill g.  s.  ad.  5iv 

(c)  Toisson's  fluid: 

Aq.  destill 160 . 0  c.c. 

Glycerin 30. 0  c.c. 

Sodii  sulphat 8.0  grams. 

Sodii  chlorid 1.0  gram. 

Methyl  violet 0 .  025  gram. 

2  Storch,  Unters.  iiber  den  Blutkorperchengehalt  des  Blutes,  etc.  Disserta- 
tion, Bern,  1901;  Musser  and  Krumbhaar,  Folia  hematologica,  xviii,  1914,  576, 
and  Wells  and  Sutton,  Am.  Jour,  of  Physiol.,  xxxix,  1915,  31. 

12 


178  THE    BLOOD 

Mill,  per  cmm. 

Goat. 14-19 

Lama 13-13 . 2 

Sheep.-. 10.3 

Cat 9.1 

Horse 7.8 

Monkevs 6.2 

Rabbit". 6.8 

Dog G.7 

Birds 2.3 

Fish  (bonv) 1.2 

Reptilia 0.5-1.6 

Amphibia :  frog 0.5 

Salamander 0 .  09 

The  average  number  of  red  corpuscles  in  one  cubic  millimeter  of 
human  blood  is  given  as  5,000,000;  in  woman,  however,  their  number 
is  somewhat  smaller,  namely,  about  4,500,000.  In  infants  a  higher 
count  is  usually  obtained  than  in  adults.  During  the  first  weeks  it 
averages  about  5,580,000,  during  the  first  and  second  years  5,680,000, 
and  from  the  second  to  the  sixth  year  seldom  under  5,900,000.  Since 
the  volume  of  a  red  cell  measures  0.000000072  cu.  mm.  and  its  surface 
0.000128  sq.  mm.,  the  total  surface  of  the  red  blood  corpuscles  present 
in  1.0  cu.  mm.  of  blood,  must  equal  640  sq.  mm.  IMoreover,  if  the 
blood  contained  in  a  mammal  is  calculated  at  i-fa  of  its  body  weight,  an 
individual  weighing  70  kg.  must  contain  about  5  kg.  of  blood.  The 
body  as  a  whole,  therefore,  gives  lodgment  to  about  25,000,000,000,000 
red  cells,  possessing  a  total  surface  of  3200  sq.  mm.  which  equals  an  area 
1500  times  greater  than  that  of  the  surface  of  the  body.^  These  figures 
clearly  betray  the  surprisingly  large  size  of  the  "breathing  surface" 
which  the  red  corpuslces  present  to  the  air  in  the  lungs  or  to  the  cells 
of  the  tissues. 

Variations  in  the  Number  of  the  Red  Blood  Corpuscles. —  While 
the  value  of  5,000,000  cells  to  the  cubic  millimeter  of  blood  remains 
fairl}'  constant  under  normal  conditions,  it  is  subject  to  certain  minor 
fluctuations.  Ordinary  physical  influences,  for  instance,  possess 
the  tendency  of  diverting  the  corpuscles  into  the  larger  vascular  chan- 
nels, while  the  blood  in  the  peripheral  vessels  contains  them  in  some- 
what smaller  numbers.  This  fact  should  be  taken  into  account  when- 
ever these  bodies  are  counted  in  accordance  with  the  method  previously 
described.  It  is  also  to  be  remembered  that  a  diminution  in  the  quan- 
tity of  the  body-fluids  may  result  at  any  time  in  consequence  of  a 
lessened  intake  of  water,  or  on  account  of  a  more  copious  discharge  of 
it  in  the  sweat,  stools  or  transudations.  In  either  case,  the  number  of 
corpuscles  per  unit  of  blood  must  become  greater.  The  reverse  result 
is  obtained  if  large  quantities  of  water  are  taken  in,  or  if  smaller 
amounts  are  excreted.     In  early  fetal  life  the  red  cells  are  fewer  in 

1  Recent  investigations  have  shown  that  in  man  the  total  amount  of  blood 
should  be  calculated  at  one-twentieth  of  the  body  weight.  The  total  surface  of 
the  red  cells,  therefore,  measures  1700  sq.  mm. 


THE  RED  BLOOD  CORPUSCLES  179 

number;  namely,  only  0.5  to  1.0  million  per  cubic  millimeter.  Their 
number  increases  later  on  so  that  infants  pres(mt  higher  values  than 
the  average  for  adults.  Pregnancy  causes  a  slight  increase  and  men- 
struation a  decrease.  Physical  exertion  at  low  altitudes  causes  a  con- 
centration of  the  blood  which  Schneider  and  Havens^  attribute  to  the 
sudden  passage  into  the  blood  of  a  large  number  of  red  corpuscles 
which  have  been  lying  dormant  in  the  body,  chiefly  in  the  splanchnic 
area.  Scott-  beheves  this  concentration  to  be  effected  by  a  passage 
of  fluid  from  the  blood  to  the  tissues,  in  consequence  of  the  higher 
blood-pressure  coincident  with  muscular  exercise.  Massage,  and 
especially  massage  of  the  abdomen,  produces  a  similar  effect  for  the 
same  reason.  During  hibernation  the  number  of  the  red  corpuscles 
is  not  materially  changed.  Neither  is  the  specific  gravity  of  the  blood, 
whereas  the  number  of  the  white  cells  is  decreased  to  about  one-half 
of  normal.^ 

A  very  interesting  phenomenon  is  the  increase  in  the  number  of 
the  erythrocytes,  resulting  whenever  high  altitudes  are  attained. 
Bert^  and  Viault,^  who  first  studied  this  change,  have  found  that  the  in- 
habitants of  low  lands  show  this  increase  whenever  they  ascend  a  high 
mountain  and  that  persons  permanently  residing  in  a  mountainous 
country,  constantly  give  counts  above  normal.  It  is  then  not  unusual 
to  obtain  increases  to  as  much  as  7,000,000  or  8,000,000  per  cu.  mm., 
but  in  most  cases  the  maximal  value  is  not  attained  until  about  twenty- 
four  hours  have  been  spent  at  the  high  altitude.  According  to  Kemp,^ 
the  number  of  the  platelets  is  also  increased,  but  the  leukocyte  count 
remains  the  same. 

Two  possibilities  present  themselves,  namely,  it  is  conceivable 
that  this  increase  is  dependent  upon  a  greater  formation  of  red  cells 
by  the  hematopoietic  tissues  or  secondly,  that  it  is  due  to  changes  in 
the  quantity  of  the  blood  plasma.  The  second  view,  originally  ex- 
pressed by  Grawitz,^  embodies  the  possibility  that  the  sojourn  in 
mountainous  regions  leads  to  a  concentration  of  the  blood,  because 
the  greater  respiratory  activity  coincident  with  muscular  exertion  and 
sweating,  occasions  a  loss  of  a  considerable  quantity  of  water. 
Gaule,  Hallion  and  Tissot,  however,  have  shown  that  an  increase  in 
the  number  of  the  red  cells  also  appears  during  balloon  ascensions, 
and  hence,  muscular  efforts  cannot  be  considered  as  the  cause  of  this 
phenomenon.  Abderhalden^  and  Bunge,^  who  also  believe  that  the 
increase  is  only  an  apparent  one,  assert  that  the  blood  is  really  made 

1  Am.  Jour,  of  Phvsiol.,  xxxvi,  1905,  239. 

2  Ibid.,  xliv,  1917,  298. 

3  Rasmussen,  Ibid.,  xli,  1916,  465. 

*  La  pression  barometrique,  Paris,  1878,  or  Compt.  rend.,  xciv,  1882,  805. 

*Compt.  rend.,  cxi,  1890,  917. 

«  Am.  Jour,  of  Physiol,  x,  1904,  34. 

^  Berliner  klin.  Wochenschr.,  xxxii,  1895,  743. 

«  Zeitschr.  fiir  Biol.,  xliii,  1902,  423. 

'  Verhandl.  des  Kongr.  f.  innere  Med.,  xiii,  1895,  192. 


180  THE    BLOOD 

"plasma-poor,"    because    a    considerable    portion    of    its  fluid  mass 
is  transferred  into  the  perivascular  lymph-spaces.^ 

The  first  view,  that  the  increase  is  real  and  is  caused  by  a  greater 
formation  of  red  cells,  possesses  the  advantage  of  being  more  closely 
in  keeping  with  physiological  facts,  but  it  must  be  admitted  that  it 
has  not  been  possible  so  far  to  ascertain  the  stimulus  which  gives  rise 
to  the  greater  activity  of  the  corpuscle-forming  organs.  Indeed,  it 
is  entirely  probable  that  several  factors  unite  in  bringing  this  change 
about.  2  The  most  interesting  of  these  is  the  influence  which  the 
barometric  pressure  exerts  upon  the  interchange  of  the  gases  in  the 
lungs.  As  the  high  altitude  is  reached,  the  tension  of  the  gases  is  dimin- 
ished and  particularly,  the  pressure  which  ordinarily  forces  the  oxj^gen 
to  combine  with  the  hemoglobin  of  the  red  corpuscles.  The  oxygen 
poverty  of  the  tissues  resulting  in  consequence  of  the  deficiency  in  the 
tension  of  this  gas,  eventually  serves  as  a  stimulus  to  intensify  the 
production  of  these  corpuscles.  Thus,  while  each  cell  is  charged  with 
a  somewhat  smaller  quantity  of  oxygen  than  normal,  the  total  amount 
of  this  gas  in  the  body  must  remain  practically  the  same,  because  the 
number  of  its  carriers  has  been  augmented.  In  substantiation  of  this 
explanation,  it  might  be  mentioned  that  Dallwig,  Kolls  and  Loeven- 
hart^  have  succeeded  in  demonstrating  that  considerable  increases 
in  the  number  of  the  erythrocytes  also  occur  in  dogs,  rabbits,  and  cats, 
when  kept  in  an  atmosphere  of  low  oxygen  concentration  even  at 
atmospheric  pressure  and  under  conditions  v/hich  do  not  require 
physical  efforts. 

A  decrease  in  the  number  of  the  red  corpuscles  is  frequently  encountered  in 
disease  (oligocythemia).  Anemias  from  all  causes  are  characterized  by  a  change 
of  this  kind,  and  clearly,  this  decrease  must  be  due  either  to  a  greater  destruction 
or  to  a  lessened  formation  of  these  cells,  or  both.  A  very  pronounced  diminution 
in  the  number  of  the  erythrocytes  is  frequently  observed  in  pernicious  anemia, 
counts  of  300,000  to  400,000  per  cu.  mm.  being  not  uncommon.  Great  numbers  of 
red  corpuscles  are  lost  in  hemorrhage,  which  it  may  take  days  and  weeks  to  replace. 
Naturally,  an  acute  hemorrhagic  anemia,  or,  more  correctly  speaking,  an  oligemia, 
is  followed  by  a  greater  production  of  red  cells,  but  the  activity  of  the  corpuscle- 
forming  organs  has  its  natural  limits  and  is  therefore  relatively  slow.  The  fluid 
parts  of  the  blood,  on  the  other  hand,  are  replaced  very  quickly,  this  end  being 
attained  by  a  lessened  discharge  of  fluid  from  the  body  and  a  transfer  of  l.ymph 
into  the  chief  circulatory  system.  In  this  way,  an  initial  hydremia  is  frequently 
developed.  Furthermore,  even  if  the  number  of  the  red  cells  has  again  risen 
to  normal,  their  hemoglobin  content  may  remain  below  normal  for  some  time 
to  come.  A  chlorotic  condition  of  a  temporary  kind  may  thus  be  developed. 
Marked  increases  in  the  number  of  the  red  cells  are  noted  at  times  in  active  patho- 
logical conditions,  but  the  hemoglobin  content  need  not  be  augmented  in  a  corre- 
sponding measure.  This  condition  in  which  counts  of  7,000,000  to  8,000,000  per 
cu.  mm.  are  encountered,  is  designated  as  polycythemia. 

1  The  assumption  that  changes  in  barometric  pressure  incite  variations  in 
the  capacity  of  the  counting  chamber,  has  been  disproved  by  Biirker. 

^  As  additional  exciting  causes  are  regarded  changes  in  temperature  and  cuta- 
neous stimuli  (Schumburg  and  Zuntz;   Pfliiger's  Archiv,  Lxiii,  1896,  461). 

^  Am.  Jour,  of  Physiol.,  xxxix,  1915,  77. 


THE    RED  BLOOD    CORPUSCLES  181 


B.  CHEMICAL  PROPERTIES 


The  Composition  of  the  Red  Corpuscles. — Different  varieties  of 
red  cells  contain  between  57  and  65  per  cent,  of  water  and  between 
35  and  43  per  cent,  of  solids.  It  may  be  said  in  general  that  they 
yield  05  per  cent,  of  water  and  35  per  cent,  of  solids.  The  latter  con- 
sist of  hemoglobin,  33  per  cent.,  protein,  0.9  per  cent.,  cholesterin  and 
lecithin,  0.46  per  cent.,  and  inorganic  salts,  such  as  potassium  phos- 
phate and  chlorid  and  sodium  chlorid,  1.4  per  cent.  Hence,  the  hemo- 
globin forms  by  far  the  largest  portion  of  the  total  solids,  namely, 
94  per  cent. 

Each  red  corpuscle  is  composed  of  a  reticular  network,  or  stroma, 
and  a  fluid  or  semifluid  portion.  The  former  appears  as  a  delicate 
spongy  and  colorless  ground  substance,  in  the  spaces  of  which  is 
deposited  the  hemoglobin,  together  with  a  small  quantity  of  water  and 
salts.  The  hemoglobin  exists  here  in  a  peculiar  amorphous  condition 
and  is  not  held  in  solution,  nor  is  it  deposited  in  crystalline  form. 

Separation  of  the  Stroma  and  Hemoglobin.  Hemolysis. — The 
procedures  usually  employed  to  isolate  the  hemoglobin  are  quite 
simple.  The  blood  may  be  frozen  and  thawed  several  times  in  suc- 
cession, or  it  may  be  diluted  with  a  small  quantity  of  distilled  water. 
It  also  suffices  to  add  to  it  a  small  amount  of  ether,  chloroform,  solanin, 
saponin,  alkalies  or  bile  acids.  Of  special  interest  are  those  bodies 
which  are  normally  present  in  some  animals  and  plants  and  which, 
when  brought  in  contact  with  blood,  cause  a  destruction  of  the  red 
cells  and  a  liberation  of  their  hemoglobin.  This  process  is  known  as 
hemolysis,  while  the  agents  concerned  in  it  are  designated  as  hemoly- 
sins. These  bodies  are  found  in  the  products  of  bacteria,  as  well  as  in 
the  venoms  and  irritating  secretions  of  snakes,  toads,  bees,  and  spiders. 
They  also  exist  in  the  normal  blood-sera  of  the  higher  animals  in  which 
they  play  an  important  part  in  the  production  of  immunity.  The 
hemoglol^in  is  liberated  by  them  either  by  causing  the  corpuscles  to 
rupture  or  by  abstracting  this  substance  from  them  withovit  marked 
injury  to  their  framework.  The  former  change  may  be  produced  by 
placing  the  corpuscles  in  water,  and  the  latter  by  adding  such  solvents 
as  ether  or  chloroform  to  the  medium  in  which  they  are  kept.  A  very 
rapid,  almost  explosive,  destruction  is  had  if  they  are  brought  in 
contact  with  bile.  When  subjected  to  any  one  of  these  agents,  the 
blood  gradually  assumes  a  much  darker  color  and  becomes  more 
transparent,  this  change  in  its  appearance  being  indicative  of  the 
escape  of  the  hemoglobin  and  its  free  dissemination  through  the  plasma. 
The  stromatic  remnants  of  the  corpuscles  are  then  designated  as 
"shadows, "  and  the  blood  as  a  whole  as  "laked"  blood. 

In  order  to  retain  the  volume  and  shape  of  the  red  cells  for  a  long  period  of  time, 
it  is  necessary  to  place  them  in  a  medium  which  is  absolutely  isotonic  to  them,  or, 
in  other  words,  in  a  solution  which  possesses  the  same  concentration  and,  therefore, 
also  the  same  osmotic  pressure  as  the  blood-serum.     The  fluid  most  commonly 


182  THE    BLOOD 

employed  for  this  purpose  is  a  solution  of  sodium  chlorid,  the  strength  of  which 
must  be  varied  somewhat  in  accordance  with  the  type  of  the  red  cell  to  be  pre- 
served. Thus,  it  is  best  to  employ  it  in  strengths  of  0.85  to  0.9  percent,  for  the 
corpuscles  of  human  blood  and  in  a  strength  of  0.8  per  cent,  for  those  of  ox  blood", 
in  fact,  the  erythrocytes  of  the  frog  require  an  even  weaker  solution,  namely,  0.70 
to  0. 75  per  cent.  It  should  not  be  forgotten,  however,  that  it  is  difficult  to  keep  a 
medium  of  this  kind  in  a  perfectly  isotonic  condition  for  any  length  of  time,  be- 
cause a  certain  loss  of  water  by  evaporation  cannot  be  avoided,  and  naturally,  as 
the  solution  becomes  more  concentrated,  it  incites  such  alterations  as  are  usually 
produced  by  hypertonic  solutions  of  any  kind. 

For  purposes  of  transfusion  a  0.75  per  cent,  solution  of  sodium  chlorid,  com- 
monly designated  as  "normal  saline,"  is  generally  made  use  of.  More  favorable 
results  may  be  obtained  at  times  bj^  employing  the  so-called  Ringer's  solution 
which  contains  the  chlorids  of  sodium,  potassium  and  calcium  in  the  following 
proportions : 

Sodium  chlorid 0.9      per  cent. 

Calcium  chlorid 0 .  026  per  cent. 

Potassium  chlorid 0 .  03    per  cent. 

Under  normal  conditions,  therefore,  the  blood  plasma  and  the  corpuscles  are 
in  a  state  of  osmotic  equilibrium,  and  while  water  passes  into  them  constantly, 
an  equal  amount  of  the  latter  is  again  discharged  into  the  plasma.  In  this  way, 
these  two  neighboring  osmotic  entities  are  enabled  to  retain  the  same  concentration, 
and  hence,  a  destruction  of  the  red  cells  cannot  take  place.  But,  naturally,  if  the 
concentration  of  the  plasma  is  either  increased  or  decreased,  the  osmotic  equilib- 
rium is  immediately  disturbed.  If  increased,  the  plasma  acts  as  a  hypertonic 
solution  and  if  decreased,  as  a  hypotonic  solution.  In  either  case,  the  change  in  its 
concentration  insures  an  alteration  in  its  osmotic  pressure,  which  immediately 
gives  origin  to  certain  interchanges  between  it  and  the  contents  of  the  corpuscle. 
Obviously,  the  purpose  of  this  transfer  is  to  reestablish  an  osmotic  balance.  Thus, 
if  the  medium  is  hypertonic,  molecules  of  water  will  continue  to  leave  the  corpus- 
cles, until  the  latter  eventually  become  greatly  reduced  in  size  and  uneven  in  outline. 
Conversely,  a  hypotonic  medium  will  cause  water  to  pass  into  the  corpuscles 
until  they  become  much  distended  and  finally  rupture,  giving  rise  to  a  great  variety 
of  abnormal  shapes. 

The  red  cells  are  regarded  by  some  authors  as  small  bags  containing  a  concen- 
trated solution  of  hemoglobin.  The  latter  is  said  to  diffuse  out  whenever  the 
enveloping  membrane  is  changed  in  such  a  way  that  it  becomes  more  permeable 
to  this  substance.  It  must  be  doubted,  however,  that  this  explanation  is  correct, 
because  the  red  corpuscles  do  not  possess  a  true  cellular  membrane  enclosing  a  free 
space,  and  because  the  hemoglobin  actually  forms  an  intricate  part  of  the  stroma. 
Hence,  the  hemoglobin  must  first  be  separated  from  the  latter,  either  by  mechan- 
ical or  chemical  means,  before  its  escape  from  the  cell  can  be  effected.  Obviously, 
a  red  cell  cannot  be  compared  with  a  receptacle  of  water  which,  on  breaking, 
discharges  its  contents  in  all  directions. 

In  order  to  separate  the  stroma  from  the  hemoglobin,  it  is  best  either  to  defibri- 
nate  the  sample  of  blood  or  to  render  it  non-coagulable  by  the  addition  of  potassium 
oxalate.  It  is  then  placed  in  the  centrifuge.  When  completely  separated,  the 
corpuscular  elements  are  washed  repeatedly  in  10  to  20  volumes  of  a  1  to  2  per 
cent,  sahne  solution  until  free  from  serum.  On  addition  of  5  to  6  volumes  of  dis- 
tilled water  containing  a  small  amount  of  ether,'  the  corpuscles  swell  up  and  dis- 
charge their  hemoglobin  into  the  surrounding  medium.  Centrifugalization  is 
resorted  to  in  order  to  accelerate  the  deposition  of  the  leukocytes.  The  supernatant 
fluid  is  treated  with  a  1.0  per  cent,  solution  of  KHSO4  until  it  acquires  the  same 

iWooldridge,  Archiv  f.  Anat.  u.  Physiol.,  1881,  387. 


THE  RED  BLOOD  CORPUSCLES  183 

density  and  appearance  as  the  original  sample  of  blood.  The  stroma  is  then 
thrown  down  by  centrifusalization  and  may  l)c  collected  upon  a  filter  and  quickly 
washed  with  distilled  water.  When  free  from  hemoglobin,  the  stroma  possesses 
poisonous  properties,  and  gives  rise  to  intravascular  clotting. 

The  constituents  of  the  stroma  are  lecithin,  cholesterin,  nucleo- 
albumin  and  a  globulin.  The  stroma  protein  forms  about  4  per  cent, 
of  the  total  sohds  of  the  red  cell  and  is  easily  dissolved  by  dilute 
alkalies  although  insoluble  in  dilute  acids. 

Great  importance  is  attached  to  the  presence  in  the  red  corpuscles 
of  lecithin  and  cholesterin  which  substances  constitute  as  much  as 
30  per  cent,  of  the  dry  weight  of  the  stroma.  Whether  these  bodies 
are  held  solely  in  the  surface  layers  or  are  contained  within  the  meshes 
of  the  stroma  is  still  doubtful,  but  it  has  been  ascertained  that  they 
determine  the  permeability  of  the  corpuscle  and  are,  therefore,  directly 
responsible  for  the  osmotic  interchanges  between  it  and  the  plasma. 
The  red  cells  are  completely  impermeable  to  the  ordinary  varieties  of 
sugar,  mammite  and  arabite,  while  water,  acids,  alkalies,  ether,  esters, 
urea  and  bile  salts  are  freely  admitted.  Amino-acids  do  not  enter 
very  readily. 

The  Constituents  of  Hemoglobin. — The  normal  circulating  blood 
contains  the  hemoglobin  either  in  the  form  of  oxyhemoglobin  or  ''re- 
duced" hemoglobin.  The  latter  is  generally  called  hemoglobin, 
because  the  term  "reduced"  is  prone  to  convey  the  erroneous  impres- 
sion that  it  has  been  formed  by  a  true  chemical  decomposition.  As  the 
name  indicates,  oxyhemoglobin  is  more  fully  charged  with  oxygen  and 
is  found,  therefore,  in  the  arterial  blood,  while  hemoglobin  proper  is 
the  normal  constituent  of  the  blood  returned  from  the  tissues. 

As  the  function  of  hemoglobin  is  to  serve  as  a  storehouse  and 
carrier  of  oxygen,  it  may  be  inferred  that  it  is  widely  distributed 
throughout  the  animal  kingdom.  It  really  plays  the  part  of  the  chloro- 
phyl  of  the  plants.  It  is  of  interest  to  note  that  it  is  not  always 
confined  to  the  blood,  but  is  also  found  in  several  tissues,  for  example, 
in  the  striated  and  cardiac  muscle  cells  of  mammals,  and  in  several 
other  tissues  of  the  lower  animals.  It  should  also  be  remembered  that 
it  is  not  always  held  in  the  corpuscular  elements  but  may  be  dissolved 
in  the  plasma.  The  ordinary  coloring  pigments,  such  as  exist  in  the 
hair,  choroid  coat  of  the  eye,  and  other  structures,  are  not  allied  to 
hemoglobin,  at  least  not  functionally. 

Hemoglobin  belongs  to  the  compound  proteids.  When  decomposed  in  the 
absence  of  oxygen,  it  yields  a  protein  called  globin  and  a  coloring  matter  designated 
as  hemochromogen.  The  latter  forms  about  4  per  cent,  of  the  molecule.  It 
contains  iron  and  maj'  be  oxidized  into  a  more  stable  body,  known  as  hematin. 
The  latter  can  also  be  obtained  in  a  more  direct  manner  by  subjecting  the  hemo- 
globin to  the  action  of  acids  or  alkalies. 

The  composition  of  oxyhemoglobin  differs  somewhat  in  different  animals,  a 
fact  which  suggests  that  it  is  subject  to  slight  modifications.  The  following 
analyses  fully  illustrate  this  point : 


184 


THE    BLOOD 


c. 

H. 

N. 
S. 
Fe 
O. 


Horse 


54.87 
6.97 

17.31 
0.65 
0.47 

19.73 
(Kossel) 


Ox 


54.66 
7.25 

17.70 
0.44 
0.40 

19.54 


Pig 


54.71 
7.38 

17.43 
0.47 
0.39 

19.60 


(Htifner) 


Dog 


53.85 
7.32 

16.17 
0,39 
0.43 

21.84 


Squirrel 


54.09 
7.39 

16.09 
0.40 
0.59 

21.44 


Hen 


52.87 
7.19 

16.45 
0.85 
0.33 

22.50 


(Hoppe-Seyler) 


According  to  Jaquet,  the  molecular  formula  of  hemoglobin  is  C758H1203N196- 
S3Fe02i8,  with  a  molecular  weight  of  16.66  grams.  Its  molecule,  therefore,  is 
extremely  large  and  complex,  a  peculiarity  which  Bunge  explains  by  saying  that, 
as  iron  is  eight  times  as  heavy  as  water,  it  must  be  united  with  a  very  large  organic 
molecule,  otherwise  it  could  not  be  floated  by  the  blood.  The  p  gment  substance 
hematin,  on  the  other  hand,  possesses  a  relatively  simple  constitution,  as  may  be 
gathered  from  the  following  formula  of  Kiister,  which  reads:  C34H34N4Fe05. 

The  Preparation  and  Quantity  of  Oxyhemoglobin. — If  blood  is 
laked  and  is  then  allowed  to  stand,  the  dissolved  hemoglobin  is  de- 
posited in  time  in  the  form  of  crystals.     It  is  to  be  noted,  however,  that 


Fig.   103. — Hemoglobin  Crystals.     (After  O.  Funkc.) 

the  speed  with  which  they  are  formed  varies  considerably.  Thus, 
they  appear  very  rapidly  in  the  laked  blood  of  the  horse,  dog  and 
guinea-pig,  and  especially  if  the  sample  of  blood  is  cooled  to-  10°  C, 
or  if  a  small  quantity  of  alcohol  is  added  to  it.  The  blood  of  the  pig, 
ox,  or  man  yields  them  with  much  greater  difficulty.  Better  results 
may  be  obtained  if  the  sample  of  blood  is  first  diluted  with  an  equal 
cjuantity  of  a  saturated  solution  of  ammonium  sulphate.  The  pre- 
cipitate, which  consists  of  globulins,  is  then  filtered  off  and  the  filtrate 
permitted  to  stand.     The  metliods   most   commonly  employed   for 


THE  RED  BLOOD  CORPUSCLES  185 

the  isolation  of  these  crystals,  are  those  described  by  Hoppe-Seyler 
as  well  as  by  Reichert  and  Brown.  ^ 

The  crystals  so  obtained  are  red  in  color  and  transparent.  Although  their  size 
is  generally  microscopic,  they  may  attain  a  length  of  2  to  3  mm.  They  appear 
as  prisms,  platelets,  tetrahedra  and  needles  of  the  rhombic  system.  From  the 
blood  of  squirrels  six-sided  plates  of  the  hexagonal  system  are  usually  obtained; 
moreover,  it  is  possible  to  change  these  into  rhombic  prisms  and  tetrahedra  by  the 
process  of  recrystallization.  They  may  he  heated  to  110-115°  C.  without  decom- 
position, but  when  subjected  to  a  temperature  of  about  160°  C,  a  reduction  results, 
the  ash  yielded  during  this  process  being  composed  largely  of  oxid  of  iron.  They 
are  soluble,  but  not  in  an  equal  measure,  because  those  most  difhcidt  to  produce 
are  most  readily  dissolved.  Very  dilute  solutions  of  the  carbonates  of  alkalies  a  e 
the  most  efficient  solvents.  Hemoglobin  is  not  easily  dialyzed.  It  does  not  diffuse 
through  parchment  membranes  and  shows  a  behavior  similar  to  that  of  colloidal 
bodies. 

Reduced  hemoglo1)in  is  more  soluble  than  oxyhemoglobin.  Its  crystals  are 
not  easily  obtained.  They  are  isomorphous  to  the  corresponding  crystals  of 
oxyhemoglobin  and  are  darker  in  color  and  pleochromatic. 

The  hemoglobin  content  of  the  blood  amounts  to  about  14  per  cent,  in  man  and 
to  13  per  cent,  in  woman.  Thus,  an  individual  weighing  70  kilos,  contains  about 
2684  grams  of  blood  and  about  491  grams  of  hemoglobin.  This  amount  is  dis- 
tributed among  25,000,000,000,000  red  corpuscles  which  present  a  total  surf  ace  of 
about  3200  square  meters.  Moreover,  as  these  bodies  are  usually  well  scattered 
and  traverse  the  capillaries  almost  "in  single  file,"  practically  all  of  the  hemo- 
globin is  made  available  for  respiratory  purposes.  It  is  also  of  interest  to  note 
that  blood  absorbs  a  much  greater  quantity  of  oxygen  than  water.  Thus,  while 
100  c.c.  of  the  latter  take  up  only  0.7  c.c,  100  c.c.  of  human  blood  assimilate 
18.5  c.c.  of  this  gas.  The  amount  of  hemoglobin  present  in  the  blood  of  the  fetus 
or  infants,  is  much  greater  than  that  found  in  the  blood  of  adults. 

Properties  of  the  Compounds  of  Hemoglobin  with  Oxygen. — The 

function  of  hemoglobin,  to  distribute  the  o.xygen  to  the  different  tissues 
of  the  body,  depends  upon  its  ability  to  unite  with  perfectly  definite 
amounts  of  this  gas.  This  union  takes  place  in  the  lungs,  where  this 
substance  is  exposed  to  the  full  pressure  of  the  oxygen  of  the  atmos- 
pheric air.  Having  absorbed  its  quota  of  the  gas,  it  is  moved  onward 
to  the  distant  tissues.  Here  the  oxygen  is  required  for  purposes  of  oxi- 
dation, and  hence,  inasmuch  as  it  is  present  in  smaller  amounts  in  the 
cells  than  in  the  blood,  it  must  be  held  under  a  greater  partial  pressure 
in  the  blood-vessel  than  in  the  tissue.  As  a  direct  result  of  this  differ- 
ence in  its  partial  pressure,  it  separates  from  the  hemoglobin  and  enters 
the  cells.  The  oxyhemoglobin  is  thus  converted  into  its  deoxidized 
or  reduced  variety.  This  property  of  the  hemoglobin  to  assimilate 
and  to  release  a  part  of  its  oxygen,  forms  the  basis  of  the  respiratory 
activity  of  the  blood. 

The  compound  of  hemoglobin  and  oxygen,  known  as  oxyhemoglobin,  can  also 
be  formed  and  destroyed  outside  of  the  body.  Thus,  if  arterial  blood  is  exposed  to 
a  vacuum,  it  frothes  and  its  color  changes  to  bluish  red  inaccordance  with  the 
amount  of  oxygen  withdrawn  from  it.     Quite  similarly,  if  venous  blood  is  shaken 

^  The  characteristics  of  the  crystals  of  hemoglobin  from  different  animals  are 
described  by  Reichert  and  Brown,  in:  The  Crystallography  of  Hemoglobins, 
Carnegie  Inst,  of  Washington,  No.  116,  1909. 


186  THE    BLOOD 

in  air  or  pure  oxygen,  it  gradually  assumes  a  much  lighter  color,  because  its  hemo- 
globin is  thereby  converted  into  oxyhemoglobin.  These  changes  may  be  considera- 
bh-  hastened  by  warming  the  blood.  The  conversion  of  oxyhemoglobin  into 
hemoglobin  may  also  be  attained  by  adding  a  reducing  agent  to  the  blood.  Such 
agents  as  ammonium  sulphid,  an  ammoniacal  solution  of  ferrous  tartrate  or  hy- 
drazin,  are  commonly  employed.' 

The  power  of  hemoglobin  to  combine  with  oxygen  seems  to  depend  upon  the  iron 
which  it  contains.  The  figures  given  above  show  that  the  amount  of  iron  varies 
only  very  slightly,  and  hence,  the  quantity  of  hemoglobin  may  be  ascertained  by 
simph'  determining  the  iron  content  of  the  blood.  One  atom  of  iron  corresponds 
to  about  two  atoms  or  one  molecule  of  oxygen. 

Methemoglobin.^ — This  body  is  a  compound  of  hemoglobin  and 
oxygen  which  does  not  occm*  normally  in  the  body.  It  appears 
\vhenever  large  amounts  of  hemoglobin  are  set  free  in  consequence  of 
an  increased  destruction  of  red  cells.  The  administration  of  such  sub- 
stances as  acetanilid,  antifebrin  and  the  nitrites  is  said  to  effect  its 
formation  in  the  circulating  blood.  It  is  also  found  in  the  urine  and 
in  the  contents  of  cysts  and  old  extravasates.  It  may  be  prepared  by 
permitting  blood  or  a  solution  of  oxj^hemoglobin  to  stand  for  a  long 
time  in  the  air,  or  by  mixing  a  sample  of  blood  with  different  oxi- 
dizing or  reducing  substances,  such  as  ozone,  potassium  permanganate, 
fei'hcyanid  or  chlorate.  Most  observers  agree  that  methemoglobin 
is  a  compound  of  hemoglobin  with  oxygen  in  which  this  gas  is  held  in 
a  different  state  of  combustion.  The  compound  is  thereby  rendered 
more  stable,  a  change  which  is  clearh"  betrayed  by  its  greater  resist- 
ance to  vacuum.  Not  being  able  to  unload  its  oxygen  freely  in  the 
tissues,  it  is  useless  as  a  respiratory-  agent. 

Methemoglobin  exhibits  a  brownish  tint  and  crvstallizes  in  needles.     Haldane 

suggests  for  oxvhemoglobin   the  formula :  Hb\       and  for  methemoglobin,  the  for- 

^O 

^^ 

mula:  Hb^     .     The  conversion  of  the  former  into  the  latter  is  not  accomplished 

^O 
directly  by  a  mere  shifting  of  the  oxygen,  but  in  an  indirect  manner,  i.e.,  by  first 
dissolving  all  the  oxygen  and  uniting  any  molecule  of  this  gas  that  may  be  available, 
with  the  radicle. 

Other  Compounds  of  Hemoglobin. —  If  blood  is  freely  exposed  to 
carbon  monoxid,  a  compound  is  formed  between  this  gas  and  the 
hemoglobin  which  is  known  as  carbon  monoxid  hemoglobin  (CO — Hb).* 
One  molecule  of  the  gas  combines  with  one  molecule  of  hemoglobin, 
thus  effecting  a  very  stable  union  which  strongly  resists  the  action 

^  Stokes's  solution  consists  of : 

Ferrous  sulphate 2.0  per  cent. 

Tartaric  acid 3.0  per  cent. 

When  about  to  use  this  solution,  add  ammonium  hydrate  until  the  precipitate 
formed  at  first  is  redissolved. 

-Discovered  by  Hoppe-Seyler,  Handb.  d.  physiol.  chem.  Analyse,  1865,  205. 
'  .Attention  was  first  called  to  this  fact  by  CI.  Bernard,  in  1HF>7. 


THE  RED  BLOOD  CORPUSCLES  187 

of  the  different  reducing  agents.  Even  air  and  pure  oxygen  are  quite 
unable  to  destroy  this  combination  with  ease.  For  this  reason,  the 
inhahition  of  coal  gas,  or  of  illuminating  gas  of  which  carbon  monoxid 
is  a  constituent,  gives  rise  to  symptoms  of  poisoning  which  are  scarcely 
less  severe  than  those  following  the  abstraction  of  oxygen  from  the  in- 
spiratory air.  Gradually,  as  the  hemoglobin  becomes  more  thoroughly 
charged  with  this  gas,  it  fails  in  an  increasing  measure  to  bind  the 
necessary  amounts  of  oxygen.  The  tissues  become  oxygen-starved 
and  eventually  cease  their  normal  activities.  Death  results,  as  a  rule, 
before  all  the  oxygen  has  been  displaced.  About  one-fifth  of  its  total 
amount  most  generally  remains  in  the  corpuscle.  Carbon  monoxid 
is  also  capable  of  uniting  with  the  oxA'gen  of  the  tissues,  thereby  de- 
stroying the  hfc  of  the  cells  themselves. 

Hemoglobin  exhibits  an  avidity  for  carbon  monoxid  which  is  140  times  greater 
than  that  for  oxygen.  Thus,  if  the  oxygen  has  been  displaced  by  carbon  monoxid, 
the  hemoglobin  cannot  easily  be  made  to  recombine  with  the  former.  For  this 
reason,  the  forcible  introduction  of  air  or  pure  oxygen  into  the  lungs  of  an  indi- 
vidual poisoned  with  coal  gas  or  water  gas,  can  have  no  other  beneficial  effect  than 
the  removal  of  that  portion  of  the  carbon  monoxid  which  has  as  yet  remained 
uncombined.  To  be  sure,  if  a  certain  number  of  corpuscles  are  still  present  which 
have  retained  their  normal  capacity  to  carry  oxygen,  the  metabolism  of  the  tissues 
may  continue  at  low  ebb  until  more  favorable  conditions  ha'^e  been  established  in 
consequence  of  an  active  regeneration  of  the  red  cells.  In  severe  cases,  however, 
which  necessitate  a  very  quick  production  of  new  oxygen-carriers,  large  quantities 
of  the  carbon  monoxid  blood  must  be  displaced  bj'  the  process  of  blood-transfusion. 

The  blood  of  a  person  poisoned  by  carbon  monoxid  gas,  possesses  a  cherrj^-red 
color.  The  muscles  and  organs,  as  well  as  the  integument,  exhibit  a  similar  dis- 
coloration. The  presence  of  very  small  quantities  of  this  gas  in  the  respiratory 
air  (J'iooo^HojOOo)  is  sufficient  to  produce  relatively  large  amounts  of  CO  hemo- 
globin. It  is  for  this  reason  that  the  admixture  of  even  very  slight  quantities  of 
this  gas  to  the  air  of  dwellings  is  so  dangerous  to  life.  It  must  be  admitted, 
however,  that  some  animals  are  more  susceptible  to  it  than  others,  which  fact  im- 
plies that  the  blood  of  animals  differs  somewhat  in  its  power  of  absorbing  this 
gas. 

Illuminating  gas  contains  another  substance,  ethylene,  which  seems  to  be 
strongly  toxic  to  trees  and  seedlings.  Its  action  upon  animals  is  not  known,  but  as 
it  is  highh'  toxic,  even  the  slightest  escape  of  illuminating  gas  should  be  carefully 
guarded  against. 

A  compound  of  even  greater  stability  results,  if  nitric  oxid  (NO)  is  brought  into 
contact  with  hemoglobin.  This  union,  however,  cannot  be  effected  in  the  body, 
because  the  ox^-gen  which  under  normal  conditions  is  always  available,  immediately 
instigates  a  reduction.  For  this  reason,  the  formation  of  this  compound  necessi- 
tates the  removal  of  the  oxygen  from  the  blood  by  hydrogen.  Hydrocyanic  acid 
(CHX)  also  enters  into  combination  with  hemoglobin,  and  it  is  also  said  that  a 
typical  sulphohemoglobin  may  be  formed. 

In  accordance  with  the  observations  of  Buckmaster  and  Gardner,  showing 
that  ether  and  chloroform  lower  the  oxygen  carrying  power  of  the  blood,  it  may 
be  surmised  that  hemoglobin  may  also  form  a  compound  with  these  agents. 
This  union  is  not  identical  with  that  ordinarily  effected  between  these  anesthetics 
and  the  lecithin  or  other  lipins  of  the  red  corpuscles. 

Derivative   Compounds   of  Hemoglobin. — The   decomposition    of 
hemoglobin  in  the  absence  of  o.xygen  gives  rise  to  hemochromogen^ 
^  Discovered  by  Hoppe-Seyler,  Zeitschr.  flir  physiol.  Chemie,  xiii,  1889,  477. 


188  THE    BLOOD 

and  in  the  presence  of  this  gas  to  hematin.  Quite  similarly,  hematin 
may  be  reduced  to  hemochromogen,  while  the  latter  substance  may  be 
oxidized  to  hematin. 

Hemochromogen  is  responsible  for  the  color  of  hemoglobin  and,  therefore,  of  the 
blood.  Solutions  of  this  substance  exhibit  a  cherry-red  color.  It  may  be  prepared 
in  crystalline  form  by  mixing  a  drop  of  defibrinated  blood  with  a  drop  of  pyridin 
to  which  a  small  quantity  of  ammonium  sulphid  is  then  added.  These  crystals 
possess    a   stellate    shape.  ^ 

Hematin  is  an  amorphous  substance  which  may  also  appear  as  rhombic  needles 
and  platelets.  2  It  possesses  a  dark-brown  color,  and  while  insohible  in  water, 
alcohol  and  ether,  is  readily  soluble  in  dilute  alkalies  and  acids.  It  has  lost 
the  properties  generally  assigned  to  a  proteid  body  and  contains  all  the  iron  of  the 
hemoglobin  molecule.     Its  formula  is  given  as  C32H3:N4Fe04.     It  is  found  in  the 


Fig.    104. — Hemix   Crystals. 

feces  after  the  ingestion  of  meats  and  food  rich  in  blood,  as  well  as  after  hemor- 
rhages into  the  stomach  or  intestinal  canal.  The  reduction  of  the  hemoglobin 
is  accomplished  in  this  case  by  the  gastric  and  pancreatic  juices. 

A  very  important  derivative  of  hematin  is  hemin  or  chlorhematin,  the  formula 
for  which  is  given  by  Kiister^  as:  C34H3304N4FeCl.  One  hydroxyl  group  of  the 
hematin  has  been  displaced  by  chlorin.  This  body  is  obtained  in  the  form  of 
crystals,  the  so-called  Teichmann's  hemincrystals.  As  these  possess  a  verj'  charac- 
teristic shape  and  color  and  may  be  derived  from  very  small  quantities  of  blood, 
the  hemin  reaction  constitutes  a  most  important  test  for  blood.  It  is  possible  to 
prepare  them  in  large  numbers  by  carefully  heating  a  droplet  of  blood  which  has 
been  placed  upon  a  glass  slide.  When  dry,  a  drop  or  two  of  glacial  acetic  acid  and  a 
small  crystal  of  sodium  chlorid  are  added,  after  which  a  cover-slip  is  applied  and 
the  acid  slowly  evaporated  by  drawing  the  slide  repeatedly  through  a  flame. 
For  purposes  of  examination,  any  dry  stain  which  is  suspected  of  being  caused  by 
blood,  must  first  be  thoroughly  washed  with  small  amounts  of  water  and  the  water 
evaporated  to  dryness,  while  solid  particles  of  blood  should  first  be  powdered 
with  a  few  crystals  of  sodium  chlorid. 

1  Donogamy,  Jahresber.  fiir  Tierchemie,  xxiii,  1894,  126. 
^  Piettra  and  Vila,  Compt.  rend.,  cxli,  1906. 
3  Zeitschr.  fiir  physiol.  Chemie,  xl,  1904,  423. 


THE  RED  BLOOD  CORPUSCLES  189 

On  examining  the  slide  under  the  microscope,  the  crystals  are  seen  singly  or  in 
clusters.  They  appear  as  rhombic  platelets  and  rods  belonging  to  the  monoclinic 
system.  In  transmitted  liglit  they  possess  a  mahogany-l)rown  color,  while  in 
direct  illvmiination  they  exhibit  a  dark  bluish  tint.  They  are  insoluble  in  water, 
alcohol,  ether  and  chloroform,  but  soluble  in  dilute  alkalies. 

Hemato porphyrin  differs  from  hemochromogen  and  hematin  in  that  it  contains 
no  iron.  Nencki^  gives  its  composition  as  C34H38N4O6  =  2Ci7Hi9N203.  It  is 
prepared  by  adding  crystallized  hemin  to  a  saturated  solution  of  hydrobromic  acid 
in  glacial  acetic  acid.  Having  permitted  this  mixture  to  .stand  for  three  or  four 
days,  it  is  shaken  with  distilled  water  and  filtered.  The  hematoporphyrin  is  then 
thrown  down  by  carefully  neutralizing  with  caustic  soda.  It  is  insoluble  in  water 
but  soluble  in  acids,  alkalies  and  ethyl  alcohol.     It  appears  as  a  dark,  violet  powder. 

The  fact  that  hematoporphyrin  is  free  from  iron  is  of  general  interest  in  so  far  as 
the  bile  pigments  are  also  iron-free  derivatives  of  hemoglobin;  indeed,  bilirubin 
and  biliverdin  are  commonly  regarded  as  excretory  products  derived  from  hemo- 
globin. The  former  pigment  is  isomeric  with  hematoporphyrin  and  both  yield 
on  oxidation  acids  which  are  identical  with  those  obtained  from  hematin.  In  this 
connection,  it  should  also  be  mentioned  that  the  decomposition  of  stagnated  blood, 
as  for  example  that  of  hemorrhagic  extravasations  into  the  brain,  gives  rise  to  a  red 
pigment,  called  hematoidin  (C3JH36N4O6)  which  is  also  free  from  iron  and  crystal- 
lizes in  clinorhombic  prisms.  This  body  is  said  to  be  identical  with  the  biliary 
pigment  bilirubin  and  to  be  isomeric  with  hematoporphyrin.  By  abstracting  one 
molecule  of  oxygen  from  the  latter,  a  body,  called  mesoporphyrin,  has  recently 
been  produced,  which  is  said  to  possess  the  same  composition  as  hematoidin. 
Traces  of  hematoporphyrin  are  generally  present  in  the  urine ;  greater  amounts  of 
it  appear  in  certain  types  of  poisoning.  Crystals  of  hematoidin  have  also  been 
found  in  the  urine  after  transfusion  of  blood  and  during  icterus,  when  there  is  a 
marked  destruction  of  red  cells.  Of  general  interest  is  the  fact  that  the  green  color- 
ing matter  of  plants,  known  as  chlorophyl,  possesses  a  chemical  structure  similar 
to  that  of  hemoglobin.  It  may  be  inferred,  therefore,  that  these  bodies  are  closely 
related  to  one  another.  This  is  shown,  moreover,  by  the  fact  that  hematoporphyrin 
may  be  reduced  to  the  oxygen-free  hemopyrrol  which  is  methylprophlpyrrol.  In 
a  similar  way,  chlorophjd  may  be  made  to  yield  phylloporphyrin,  a  body  closely 
allied  to  hematoporphyrin  which   in  turn  may  be  changed  into  hemopyrrol. ^ 

CLINICAL  METHODS  FOR  THE  DETERMINATION  OF  HEMOGLOBIN 

The  hemoglobin  content  of  the  blood  varies  very  slightly  under 
normal  conditions,  but  fluctuates  considerably  in  disease.  Two  fac- 
tors may  be  held  responsible  for  this  inconstancy,  namely,  a  change 
in  the  number  of  the  red  cells  or  a  change  in  their  capacity  to  carry 
hemoglobin.  Wliile  these  changes  may  arise  independently  of  one 
another,  they  are  more  frequently  found  to  be  associated  with  one 
another.  In  the  second  place,  it  should  be  remembered  that  they 
need  not  pursue  a  perfectly  parallel  course,  because  it  frequently 
happens  that  a  reduction  in  the  hemoglobin  content  is  associated  with 
an  increase  in  the  number  of  the  red  cells.  Conversely,  a  decrease  in 
their  number  cannot  justly  be  regarded  as  a  certain  indication  of  a 
loss  in  the  total  amount  of  hemoglobin,  because  the  individual  corpus- 
cles may  contain  larger  amounts  of  it. 

1  Monatshefte  fiir  Chemie,  x,  1889,  568;  and  Zeitschr.  fur  physiol.  Chemie, 
XXX,  1900,  384. 

2  Nencki  and  Marchlewski,  Ber.  der  chem.  Gesellsch.,  xxxiv,  1901. 


190  THE    BLOOD 

As  a  disturbance  in  the  relationship  of  these  two  factors  is  most 
likely  to  result  in  consequence  of  pathological  conditions,  it  is  essential 
to  be  in  possession  of  a  quick  and  accurate  method  for  the  quantitative 
determination  of  this  substance.  It  is  quite  true  that  a  knowledge  of 
the  hemoglobin  content  of  the  blood  freciucntly  facilitates  the  diag- 
nosis, but,  as  has  just  been  emphasized,  this  value-must  first  be  brought 
into  relation  with  the  number  of  the  red  cells,  otherwise  it  may  give 
rise  to  veiy  erroneous  deductions  regarding  the  general  condition  of 
the  blood.  Two  methods  have  been  advocated  for  the  determination 
of  hemoglobin.  One  of  these  has  been  described  by  Welker  and  Hoppe- 
Seyler,^  and  is  known  as  the  chronometric.  The  other,  described  by 
Vierordt  and  Glan,^  is  known  as  the  spectrophotometric.  The  various 
modifications  of  the  first  take  the  normal  quantity  of  hemoglobin  to 
be  100  per  cent,  and  the  normal  number  of  the  red  corpuscles  (5,000,000 
per  cu.  mm.)  also  100  per  cent.  The  color  exhibited  by  a  sample  of 
blood  of  this  quahty  is  regarded  as  unitj^;  this  standard  being  obtained 
by  employing  the  percentage  of  hemogloljin  as  the  numerator  and  the 
percentage  of  the  corpuscles  as  the  denominator.  Thus,  if  the  num- 
ber of  the  red  cells  remains  the  same,  while  their  hemoglobin  content 
is  diminished,  the  color  index  becomes  smaller  than  1.     A  reduction 

80 
of  the  hemoglobin  to  80  per  cent,  gives  an  index  of  j^   =  0-8,  which 

c 
value  implies  that  the  different  corpuscles  carry  only   -^  of  the   normal 

quantity  of  hemoglobin.  Under  certain  pathological  conditions  the 
decrease  in  the  percentage  of  hemoglobin  is  often  associated  with  a 
diminution  in  the  percentage  of  the  corpuscles;  moreover,  the  reduc- 
tions may  or  may  not  be  equally  great  in  the  two  cases.  If  they  are 
equal,  the  color  index  is  1,  and  if  they  are  not,  the  latter  is  either  smaller 
or  larger  than   1.     To  illustrate,   assuming  that  the  percentage  of 

hemoglobin  is  60  and  the  percentage  of  corpuscles  80,  the  index:  ^  = 

0.75,  suggests  that  the  different  corpuscles  are  loaded  with  only  three- 
fourths  of  the  amount  of  hemoglobin  ordinarily  carried  by  them. 
And  again,  a  percentage  of  hemoglobin  of  60  and  a  percentage  of  red 

cells  of  50  gives  the  index:--  =  1.2,  which  indicates  that  the  hemo- 

globin  content  of  the  individual  corpuscles  is  greater  than  normal. 

The  principle  involved  in  this  method  is  the  following:  If  two  solutions  in 
identical  receptacles  are  exposed  to  the  same  source  of  light  and  exhibit  the  same 
color,  their  content  in  coloring  matter  must  be  the  same.  Hence,  it  should  be 
possible  to  prepare  a  solution  of  hemoglobin  of  known  concentration  and  to  deter- 
mine the  hemoglobin  content  of  other  samples  of  blood  by  simply  comparing  them, 
with  this  standard  solution.  But,  as  standard  solutions  of  this  kind  cannot  always 
be  easily  kept,  the  attempt  was  made  at  an  early  date  to  find  a  more  permanent 

1  Zeitschr.  fiir  physiol.  Chemie,  xv,  xvi,  xxi,  1891,  1892,  and  1896. 

2  Poggend.  Ann.,  1877. 


THE    RED    BLOOD    CORPUSCLES 


191 


colometric  substitute;  for  example,  solutions  of  the  more  stable;  compounds  of 
hemoglobin,  solutions  of  picrocarmin  and  colored  glass. 

The  instruments  which  have  been  devised  to  permit  of  a  comparison  of  this 
kind  are  called  he iiioglobino meters,  or  hemo- 
meters.  Hoppo-Seyler  employed  two  glass 
troughs  with  parallel  sides,  into  one  of 
which  he  placed  a  standard  solution  of  oxy- 
hemoglobin of  known  strength,  and  in  the 
other,  the  blood  to  be  tested.  The  pro- 
cedure consisted  in  diluting  the  sample  of 
blood  until  its  color  corresponded  precisely 
with  that  of  the  standard  .soluticm.  The 
quantity  of  water  necessary  to  attain  this 
end,  enables  one  to  calculate  the  propor- 
tion of  hemoglobin  in  the  undiluted  blood. 
The  procedure  advocated  by  TallqvLst,' 
consists  in  permitting  a  drop  of  blood  to 
fall  upon  white  filter  paper.  When  evenly 
diffused  the  color  of  the  stain  is  compared 
with  similar  permanent  stains  indicating 
the  different  percentages  of  hemoglobin 
from  10  to  100.  The  hemo photographic 
method  of  Gartner- is  based  upon  the  fact 
that  a  solution  of  oxyhemoglobin  absorbs 
the  rays  of  light  in  a  steadily  increasing 
measure  with  its  concentration.     Fleischl's 

instrument^  consists  of  a  short  cylindrical  receptacle  which  is  divided  into  two  com- 
partments by  a  vertical  median  partition.     Into  one  of  these  is  placed  a  measured 


Fig.   105. — Hemoglobinometer. 
{Flei.ichr.s.) 

S,  stage;  R,  reflecting  mirror;  B, 
screw  for  adjusting  position  of  colori- 
metric  wedge;  A,  the  cylindrical  re- 
ceptacle. C,  contains  two  compart- 
ments into  one  of  which  is  placed 
the  sample  of  blood  to  be  examined. 


n/7 


—  ^0 

_ao 

—  70 

—  fco 
SO 

—  "fO 

—  30 

—  10 

—  10 


^ry 


V 


IQcmn* 


D 

(Gowers.) 
blood ;   C,  receptacle  for  distilled 


A        B  C 

Fig.  106. — Hemoglobinometer. 
A,  tube  filled  with  colored  fluid;  B,  tube  for  mixing 
water  with  dropper;  D,  pipet. 

'  Berliner  klin.  Wochenschr.,  1904. 
2  Miinchener  med.  Wochenschr.,  1901. 

^Wiener  med.  Jahresb.,    1885;  modified  by   Miescher,   Korresp.  f.  Schweizer 
Arzte,  xxiii,  1893. 


192  THE    BLOOD 

quantity  of  the  blood  to  be  tested  plus  a  definite  amount  of  water.  A  glass  wedge 
is  situated  beneath  the  other  compartment,  stained  in  different  reds  to  correspond 
to  the  color  of  different  solutions  of  hemoglobin  of  known  concentration.  This 
scale  is  then  moved  onward  until  its  color  corresponds  precisely  with  that  of  the 
sample  of  blood.  Thus,  if  the  colors  are  matched,  say,  at  division  75  of  the  scale, 
the  blood  contains  only  75  per  cent,  of  the  normal  quantity  of  hemoglobin.  Mies- 
cher  has  endeavored  to  obviate  the  use  of  solutions  and  has  succeeded  in  producing 
an  instrument  of  even  greater  precision  than  that  of  Fleischl.  Gower's  hemoglo- 
hinometcr'^  which  is  the  one  most  commonly  employed  to-day,  consists  of  two  iden- 
tical glass  tubes,  A  and  B  (Fig.  106).  Tube  A  is  filled  with  glycerin-jelly  to  which 
picrocarmin  has  been  added  until  its  color  corresponds  precisely  to  that  of  a  1 
per  cent,  solution  of  hemoglobin,  i.e.,  to  that  of  normal  blood  diluted  100  times. 
Tube  B  is  filled  with  20  cu.  mm.  of  blood  t-o  which  a  few  drops  of  distilled  water 
have  been  added  to  prevent  coagulation.  Water  is  then  dropped  into  this  re- 
ceptacle by  means  of  a  pipet  until  the  color  of  the  diluted  blood  corresponds  pre- 
cisely with  that  of  the  standard  solution  in  tube  A.  The  gradations  upon  tube  Z> 
accurately  represent  the  percentage  of  hemoglobin.  It  is  necessary-  to  transpose 
the  tubes  repeatedly.  Thus,  if  the  original  20  cu.  mm.  of  blood  are  matched  at 
division  80,  the  blood  contains  but  80  per  cent,  of  its  normal  amount  of  hemo- 
globin. The  following  modification  of  this  method  has  been  suggested  by  Hal- 
dane.-  In  tube  A  is  placed  a  1  per  cent,  solution  of  blood  saturated  with  carbon 
monoxid.  Having  dropped  20  cu.  mm.  of  blood  plus  a  slight  amount  of  distilled 
water  into  tube  B,  the  hemoglobin  contained  in  it  is  quickly  converted  into  carbon 
monoxid  hemoglobin  by  charging  it  with  pure  carbon  monoxid  or  by  passing  a 
mixture  containing  this  gas  through  it.  The  dilution  of  the  sample  of  blood  is 
then  accomplished  in  the  manner  described  pre\'iou.sly.  Sahli^  employs  a  solution 
of  hematin  chlorid  and  first  converts  the  blood  to  be  tested  into  hematin  chlorid. 

SPECTROSCOPIC  ANALYSIS  OF  HEMOGLOBIN  AND  ITS  DERIVATIVE 

COMPOUNDS 

The  most  essential  part  of  the  spectroscope  is  a  glass  prism  P, 
which  receives  a  bundle  of  white  light  through  tube  A  (Fig.  107). 
The  size  of  this  bundle  may  be  varied  b}'  altering  the  size  of  the  slit- 
like opening  in  the  end  of  this  tube,  while  a  biconvex  lens  interposed  in 
this  place  serves  to  render  the  raj^s  parallel  and  to  concentrate  them 
upon  the  surface  of  the  prism  at  C.  The  spectral  components  of  the 
white  light  are  observed  in  magnified  fonn  through  tube  B  which  is 
nothing  more  than  a  small  telescope.  The  third  tube  D  contains  a 
scala  M  which  is  illuminated  and  reflected  upon  the  surface  of  the 
prism  at  C.  In  this  way,  the  spectral  colors  (red  to  violet)  may  be 
observed  in  conjunction  with  the  divisions  of  the  scala. 

If  a  colored  medium,  for  example,  a  solution  of  hemoglobin  is  now 
placed  between  the  source  of  hght  and  the  opening  in  tube  A,  some  of 
the  rays  of  white  light  are  prevented  from  entering,  i.e.,  they  are  ab- 
sorbed. In  consequence  of  this  absorption,  certain  sections  of  the  spec- 
trum as  observed  through  tube  B,  appear  in  different  shades  of  black. 
These  dark  bands  situated  in  between  the  different  colors,  are  com- 
monly called  absorption  bands.     Of  greatest  importance,  however,  is 

1  The  Lancet,  1878. 

2  Jour,  of  Physiol.,  xxvl,  1901,  497. 

^  Lehrbuch  der  klin.  Untersuchungsmeth.,  1905. 


THE  RED  BLOOD  CORPUSCLES 


193 


the  fact  that  different  substances  affect  the  spectrum  in  very  specific 
waj^s  so  that  it  is  possible  to  determine  their  presence  by  the  number, 
intensity  and  location  of  the  al)sorption  l)ands.  But,  as  some  of  these 
bands  occupy  the  same  or  very  nearly  the  same  positions,  it  is  desira- 
ble to  possess  certain  landmarks  in  the  spectrum  for  our  guidance. 
This  purpose  is  served  by  the  Fraunhofer  lines.  The  spectrum  of  sun- 
light extends  between  the  ultra  red  and  ultra  violet  colors,  i.e.,  between 
rays  possessing,  on  the  one  hand,  a  wave  length  of  7o7/x/i,^  and,  on  the 
other,  one  of  392/i;u.  The  Fraunhofer  lines  traverse  the  spectrum  at 
definite  distances  from  one  another.  Thus,  the  i?-line  transects  the 
red  end  with  a  wave  length  of  686.8^1^,  the  Z)-line  the  golden  yellow 
with  a  length  of  589/x/i,  and  the  J^-liue  the  green  with  a  length  of  vibra- 
tion of  blljjLjj.. 


Fig.   107. — Diagram  of  Spectroscope. 


The  spectrum  of  oxyhemoglobin  is  a  very  characteristic  one.  Two  absorption 
bands  are  visible  at  the  border  of  yellow  and  green,  between  the  Fraunhofer  D-  and 
JS'-lines  (Fig.  108).  The  left  band  is  narrow  but  dark  and  sharp  and  is  generally 
designated  as  the  "a-band."  The  one  on  the  right,  which  is  broad  and  less 
clearly  outlined,  is  referred  to  as  the  "jS-band."  But  as  the  absorption  of  the 
light  is  dependent  upon  the  thickness  and  the  concentration  of  the  solution,  these 
bands  are  not  always  equally  distinct.  Thus,  if  the  percentage  of  oxyhemoglobin  is 
greater  than  0.65,  the  bands  coalesce  and  the  yellow-green  color  between  them 
disappears.  Greater  concentrations  eventually  give  rise  to  one  dark  band  which 
overlaps  the  D-  and  £'-lines  and  causes  a  darkening  of  the  violet  end  of  the  spectrum. 
Quite  similarly,  very  dilute  solutions  (0.01-0.003  per  cent.)  produce  only  a  single 
band,  namely,  the  one  nearest  the  D-line.  It  is  essential,  therefore,  to  employ 
solely  solutions  in  strengths  of  from  0.1  to  0.6  per  cent.,  while  the  layer  of  the 
solution  should  be  1  cm.  in  thickness.  These  bands  may  also  be  obtained  from 
circulating  arterial  blood.  A  good  object  for  this  purpose  is  the  ear  of  the  rabbit, 
a  hand  spectroscope  being  applied  directly  to  its  surface. 

Reduced  hemoglobin  gives  only  one  absorption  band  which  is  commonly 
spoken  of  as  the  "7-  band. "  It  is  situated  between  the  D-  and  E'-lines,  extending 
farther  toward  the  red  end  of  the  spectrum  and  slightly  beyond  the  D-line.  It 
exhibits  a  considerable  width  and  rather  poorly  defined  margins,  but  its  character- 
istics vary  somewhat  with  the  strength  of  the  solution. 

The  spectrum  of  hemoglobin  and  its  oxygen  combination  is  invariably  made  use 
of  in  the  detection  of  blood,  the  suspected  substance,  smear  or  stain  being  first 
extracted  with  a  definite  quantity  of  normal  saline  solution.     In  these  examinations 


1  l;u/x  =  1  millionth  of  a  millimeter. 


13 


194 


THE    BLOOD 


the  attempt  must  also  be  made  to  convert  the  oxyhemoglobin  into  hemoglobin  and 
the  latter  into  tlie  former.  Thus,  if  a  certain  solution  yields  the  a-  and  /3-bands, 
a  reducing  agent  should  be  added  to  obtain  the  7-band,  because  this  conversion 
establishes  the  presence  of  blood  with  much  greater  certainty  than  the  presence 
of  the  first  two  bands  alone.  Quite  similarly,  a  solution  in  whicli  hcmoglol)in  has 
been  proved  to  exist  spectroscopically,  shoidd  be  oxidized  by  shaking  it  until  the 
7-band  is  eventually  displaced  by  the  two  bands  of  oxyhemoglobin. 

Solutions  of  carbon  monoxid  hemoglobin  also  give  two  absorption  bands 
which  may  be  mistaken  at  times  for  those  produced  bj^  oxyhemoglobin;  however, 
a  differentiation  is  readily  possible  if  the  solutions  are  properly  diluted.  When  this 
has  been  done,  the  superposition  of  the  different  spectra  so  far  described,  will  show 
that  the  bands  of  carbon  monoxid  hemoglobin  are  situated  somewhat  nearer  the 
blue  end  of  the  spectrum;  and  besides,  they  are  permanent  in  character,  i.e., 
they  cannot  be  fused  into  a  single  one  by  the  addition  of  a  reducing  agent. 


Fig.  108. — The  spectra  of  oxyhemoglobin  in  different  grades  of  concentration,  of 
reduced  hemoglobin,  and  of  carbonic  oxid  hemoglobin.  {After  Preyer  and  Ganger.) 
1  to  4.  Solution  of  oxyhemoglobin  containing:  (1)  less  than  .01  per  cent.,  (2)  .09  per 
cent.,  (3)  .37  per  cent.,  (4)  .8  per  cent.  5.  Solution  of  (reduced)  hemoglobin  containing 
about  .2  per  cent.  6.  Solution  of  carbonic  oxid  hemoglobin.  In  each  case  of  the  six 
cases  the  layer  brought  before  the  spectroscope  was  1  em.  in  thickness.  The  letters 
indicate  Fraunhofer  lines  and  the  figures  wave-lengths  expressed  in  Jioo.ooo  millimeter. 


Nitric  oxid  hemoglobin  shows  two  absorption  bands  which  are  paler  and  less 
distinct  than  those  of  carbon  monoxid  hemoglobin  and  furthermore,  their  charac- 
teristics cannot  be  altered  by  reducing  agents. 

The  absorption  bands  of  methemoglobin  in  watery  or  acidified  solutions  are  very 
similar  to  those  of  acid  hematin,  which  body  gives  three  to  four  distinct  bands. 
A  differentiation,  however,  can  easily  be  effected,  because  methemoglobin  when 
mixed  with  a  small  quantity  of  an  alkali  and  a  reducing  agent,  shows  the  absorp  ion 
band  of  reduced  hemoglobin,  while  under  precisely  the  same  conditions  hematin 
exhibits  the  spectrum  of  an  alkaline  hemochromogen  solution.  In  alkaline 
solutions  this  substance  shows  three  bands,  two  of  which  are  similar  to  those  of 
hemoglobin.  They  differ  from  the  latter  in  that  the  jS-band  is  more  conspicuous 
than  the  a-band;  moreover,  the  latter  occurs  in  relation  with  a  third  band  which  is 
fainter  and  occupies  a  position  somewhat  to  the  left  of  the  D-line. 


THE  RED  BLOOD  CORPUSCLES  195 

Hemochromogen  in  acid  solution  has  four  hands  and,  in  alkaline  solution, 
two  hands.  Ono  of  the  latter  is  dark  and  is  situated  between  the  D-  and  ^^-lines, 
while  the  other  is  less  intense  and  covers  the  ^'-line. 

Acid  hematin  possesses  a  shari)ly  defined  absorption  band  between  the  C-  and  D- 
lines,  the  position  of  which  varies  somewhat  with  the  type  of  tlie  solution  employed. 
A  second  band,  much  broader  but  less  intense,  is  present  between  the  Z^-and  /^-lines. 
By  proper  dilution  this  band  may  be  converted  into  two.  The  one  nearest  the  FAma 
is  dark  and  broad,  and  the  one  nearest  E,  Yi^hi  and  narrow.  Another  very  faint 
band  may  be  made  out  near  D  by  diluting  the  liquid  still  further.  Hematin  in 
alkaline  solution  presents  one  broad  absorption  l^and  located  principally  between 
the  C-  and  /Wines,  but  extcndinp;  slightly  into  the  space  to  the  right  of  D. 

On  addition  of  a  few  drops  of  hydrochloric  acid,  an  alcoholic  solution  of  hema- 
toporphyrin  presents  two  bands,  nainely,  one  near  D  which  is  narrow  and  faint,  and 
one  between  D  and  E  which  is  broad  and  sharply  outlined.  A  dilute  alkaline 
solution  of  this  substance  presents  four  bands,  namely,  one  between  C  and  D,  one 
between  D  and  E  and  covering  /),  one  between  D  and  I']  and  very  close  to  £?and 
lastly,  one  near  F.  With  the  aid  of  an  alkaline  zinc  chlorid  solution  these  bands 
may  be  made  to  coalesce  into  two,  namely,  into  one  located  at  D  and  one  situated 
between  D  and  E.  In  acid  solutions  this  substance  frequently  shows  four 
bands,  but  much  depends  upon  the  manner  in  which  the  solution  is  prepared. 


THE  LIFE  HISTORY  OF  THE  RED  CORPUSCLES 

In  the  embryo  the  I'td  cells  originate  in  the  so-called  vascular 
area.  The  blood-vessels  appear  at  this  time  as  a  network  of  solid 
threads,  differentiated  from  the  adjoining  tissue  by  a  greater  opacity. 
Their  walls  are  made  up  of  masses  of  cells  which  are  intermingled 
with  ameboid  corpuscles  and  of  cells  which  possess  a  peculiar  branched 
appearance.  Later  on,  when  fluid  has  forced  its  way  into  the  different 
tubules  from  without,  the  cells  on  the  outside  arrange  themselves  in 
the  form  of  an  endothelial  lining,  while  loose  clusters  of  large  globular 
cells  project  from  here  into  the  lumen  of  the  vessel.  All  these  cells 
multiply  very  rapidly  by  indirect  division.  The  cytoplasm  of  those 
fastened  to  the  inside  wall  is  colorless  and  nucleated  at  first,  but 
gradually  acquires  a  certain  quantity  of  hemoglobin.  These  cells 
become  yellowish  in  color  and  eventually  separate  to  assume  a  position 
in  the  fluid  within  the  channel.  Being  still  in  possession  of  a  nucleus, 
they  are  capable  of  multiplying  by  indirect  division.  Later  on,  how- 
ever, as  the  individual  tubules  acquire  a  larger  size  and  begin  to  anas- 
tomose with  one  another,  these  newly  developed  cells,  in  which  we 
recognize  the  red  corpuscles,  migrate  into  the  general  circuit  and  hence- 
forth lead  an  independent  life. 

During  the  later  stages  of  embryonic  development,  other  organs 
enter  into  the  formation  of  these  elements.  To  begin  with,  this  func- 
tion is  centralized  in  the  liver;  subsequently,  however,  the  spleen, 
lymphatic  tissues  and  red  marrow  of  the  bones  take  part  in  their 
production.  During  the  last  periods  of  embryonic  existence  the  im- 
portance of  the  liver  and  spleen  as  corpuscle-forming  organs  decreases 
very  markedly,  while  that  of  the  bone  marrow  increases  steadily 
until  the  end  of  fetal  life. 


196  THE    BLOOD 

During  the  earh'  stages  of  embryonic  existence,  the  precursors 
of  the  red  corpuscles,  generally  known  as  erythroblasts,  are  large 
and  nucleated,  while  the  non-nucleated  cells  which  are  so  char- 
acteristic of  the  adult  animal,  appear  at  a  much  later  time.  In  the 
human  fetus,  for  example,  all  the  cells  are  nucleated  at  the  end  of  the 
fourth  week,  while  at  the  end  of  the  third  month  only  about  one- 
fourth  of  their  total  number  is  still  in  possession  of  a  nucleus.  The 
corpuscles  of  the  latter  type  become  fewer  and  fewer  in  number  as 
gestation  advances  until  at  birth  practically  all  the  circulating  ery- 
throcytes are  without  a  nucleus.  Only  those  which  are  still  retained 
in  the  corpuscle-forming,  or  hematopoietic  tissues,  remain  nucleated. 
Naturalty,  the  loss  of  the  nucleus  wliich  occurs  either  by  disintegration 
or  extrusion,  implies  that  they  are  now  fully  developed  and  also,  that 
they  no  longer  multiply  by  simple  diA'ision. 

The  formation  of  the  red  corpuscles  does  not  cease  at  the  end  of 
intrauterine  existence,  but  is  continued  throughout  the  life  of  the 
animal;  and  furthermore,  as  their  number  does  not  increase,  their 
formation  must  be  counterbalanced  by  an  adequate  destruction. 
That  this  is  true  may  be  inferred  from  many  experiments.  Thus,  if 
a  loss  of  red  corpuscles  is  effected  by  bleeding,  the  fluid  parts  of  the 
blood  are  quickly  replaced  by  transferring  a  certain  quantity  of  the 
tissue-lymph  into  the  vascular  system.  Consequently,  the  blood  is 
relatively  poor  in  corpuscles  directty  after  the  hemorrhage,  but  ac- 
quires them  in  greater  numbers  later  on  as  new  ones  are  sent  in  by  the 
hematopoietic  tissues.  An  interval  of  a  few  days  generally  suffices 
to  establish  the  normal  corpuscle  count,  but  naturally,  much  depends 
upon  the  quantity'  of  blood  lost  and  the  activit}^  of  the  corpuscle- 
forming  tissues.  A  second  fact  that  should  be  mentioned  at  this  time 
is  the  constant  outgo  of  pigmentous  material  in  the  feces  and  urine, 
in  the  form  of  urochrome,  urobilin  and  stereobilin.  It  has  been  shown 
that  these  substances  originate  in  the  liver  and  that  their  production 
is  closely  dependent  upon  the  amount  of  hemoglobin  available  for 
this  purpose.  By  inference,  therefore,  it  may  be  concluded  that  a 
supply  of  this  coloring  material  must  be  constantly  at  hand;  i.e., 
it  must  be  brought  to  this  organ  by  the  red  cells  in  undiminishing 
quantities. 

During  extrauterine  life  the  erythrocytes  are  formed  in  the  red 
marrow  of  the  bones.  jMarrow  of  this  color  is  found  in  the  flat  and 
short  bones  of  the  head  and  trunk  and  in  the  long  bones  of  the  ex- 
tremities. The  latter,  however,  contain  it  solely  in  their  ends.  It  is 
also  to  be  noted  that  the  yellow  marrow  in  the  other  regions  of  these 
bones  may  assume  the  characteristics  of  red  marrow  at  any  time  when 
a  very  active  regeneration  of  the  red  cells  is  called  for.  The  fatty 
marrow  in  the  diaphyses  then  becomes  filled  with  a  red  pasty  mass 
consisting  chiefly  of  red  cells  and  their  precursors.  This  conversion 
may  readily  be  induced  in  animals  by  bleeding.  A  similar  change  has 
been  observed  in  hibernating  animals.     Red  marrow  is  formed  very 


THE  RED  BLOOD  CORPUSCLES  197 

rapidly  in  the  spiinp;,  while,  at  the  beginning;  of  the  period  of  hiberna- 
tion, the  yellow  marrow  is  present  in  especially  large  amounts.' 
In  the  frog,  lymi)h()i(l  red  marrow  appears  only  in  the  early  summer, 
which  fact  indicates  that  this  animal  obtains  a  considerable  supply  of 
new  red  cells  at  this  time  of  tlie  year.- 

Th(^  precursors  of  the  red  cells  are  called  erythroblasts,  while  the 
process  by  means  of  which  these  cells  are  converted  into  mature  red 
corpuscles,  is  known  as  hematopoiesis.  Their  migration  into  the 
blood-stream  is  greatly  facilitated  by  the  circulatory  conditions  exist- 
ing in  the  marrow.  In  the  first  place,  it  is  to  be  noted  that  these 
channels  are  protected  by  unyielding  bony  walls,  while  their  cellular 
lining  is  thin  and  rather  imperfect.  And  besides,  as  the  rapidity  of 
the  blood  flow  is  slight  and  the  pressure  low,  a  certain  traction  is 
brought  to  bear  upon  them,  but  naturally,  the  quickness  with  which 
they  are  formed  and  are  forced  into  the  circulation,  depends  in  a  large 
measure  upon  how  greatly  the  system  is  in  need  of  them.  Thus,  it  is 
possible  to  retard  the  production  of  these  elements  in  such  a  degree 
that  the  lumen  of  the  vessels  becomes  practically  free  from  them, 
while  the  region  close  to  their  wall  is  filled  with  cells  in  all  intermediary 
stages  of  development.  It  is  also  possible  to  stimulate  the  hemato- 
poietic process  bj'-  causing  a  greater  destruction  of  the  circulating  red 
cells.  This  end  may  be  attained  either  by  bleeding,  or  by  the  adminis- 
tration of  toxic  substances.  The  histological  picture  then  obtained 
is  quite  different  from  that  just  given,  because  the  lumen  of  the  chan- 
nel is  now  filled  with  young  erythrocytes,  many  of  which  are  still  in 
possession  of  a  nucleus.  Some  of  these  nucleated  cells  find  their  way 
into  the  general  circulation,  where  they  are  recognized  as  normohlasts. 
Under  certain  pathological  conditions  the  liver  and  the  spleen  seem 
to  regain  the  corpuscle-forming  power  which  they  possessed  during 
embryonic  life. 

While  the  duration  of  the  life  of  the  red  cells  has  been  estimated  at 
about  four  weeks,  it  cannot  be  said  that  this  point  has  been  definitely 
settled.  The  attempt  has  been  made  to  arrive  at  a  conclusion  by 
introducing  a  limited  number  of  elliptical  corpuscles  into  the  circula- 
tion of  a  mammal.  It  seems,  however,  that  the  length  of  time  during 
which  the  cells  of  the  lower  forms  or  of  birds  continue  to  live  in  the 
mammalian  blood,  cannot  be  regarded  as  a  safe  guide,  because  as  they 
are  thus  placed  into  a  medium  which  is  foreign  to  them,  they  may  go 
to  pieces  much  sooner  than  they  would  otherwise.  Another  method 
to  which  brief  reference  should  be  made  here,  depends  upon  the  deter- 
mination of  the  number  of  red  cells  w^hich  must  be  destroyed  daily 
in  order  to  permit  of  the  excretion  of  the  usual  amounts  of  bile  pig- 
ment. If  the  quantity  of  bile  is  15  grams  per  kilo  of  the  body  weight 
and  the  percentage  of  its  pigment  0.2,  the  daily  output  of  pigment 
must  amount  to  1.95  grams.     But  in  order  to  obtain  this  quantity  of 

'  Pappenheim,  Zeitschr.  fiir  klin.  Med.,  xliii,  1901,  363. 
2  Marquis,  Dissertation,  Dorpat,  1892. 


198  THE    BLOOD 

pigment,  48  grams  of  hemoglobin  must  be  made  available,  i.e.,  about 
one-tenth  of  the  total  amount  of  this  substance  ordinarily  present  in 
an  individual  weighing  65  kilos  and  possessing  about  3500  grams  of 
blood.  Upon  the  basis  of  this  calculation,  the  life  of  the  circulating 
red  corpuscle  may  be  said  to  be  about  ten  days.  Our  long  cherished 
beliefs  regarding  the  production  of  bile  pigments,  however,  do  not 
agree  with  the  views  of  Hooper  and  Whipple,  ^  because  it  seems  that 
the  liver  possesses  a  certain  inherent  power  to  form  pigment,  thus 
quite  offsetting  the  calculation  just  given.  A  relatively  severe  loss  of 
red  corpuscles,  which  must  be  compensated  for  immediately,  occurs 
during  the  menstrual  flow.  Mix^  states  that  150  c.c.  of  blood  are  lost 
during  this  period  which  are  again  reformed  in  the  course  of  about 
twenty-eight  days.  This  necessitates  the  formation  of  5000  cu.  mm. 
of  blood  in  a  day,  208  cu.  mm.  in  an  hour  or  3.5  cu.  mm.  in  a  minute. 
The  total  number  of  red  corpuscles  lost  during  this  period,  necessitates 
the  formation  of  15,750,000  new  cells  in  a  minute. 

It  seems  that  the  disintegration  of  the  red  cells  begins  while  they 
traverse  the  general  circulatory  channels,  but  their  absolute  destruc- 
tion and  dissolution  is  restricted  to  two  organs,  namely,  to  the  liver 
and  the  spleen.  Moreover,  it  is  very  probable  that  the  former  organ 
possesses  a  much  greater  disintegrating  power  than  the  latter,  which 
belief  may  be  substantiated  by  the  following  facts: 

(a)  The  liver  is  the  place  in  which  the  hematin  is  changed  into  bile  pigment, 
and  hence,  an  adequate  supply  of  the  former  substance  must  always  be  kept  on 
hand. 

(6)  The  hepatic  cells  contain  iron  which  is  normally  derived  from  the  red 
corpuscles.  This  fact  may  be  established  by  treating  a  cross-section  of  this 
organ  with  potassium  ferrocyanid  and  acid  alcohol,  under  which  condition  it 
assumes  a  blue  color.  While  a  part  of  the  iron  is  excreted,  a  part  of  it  is  reabsorbed 
and  may  again  be  employed  in  the  formation  of  new  corpuscles. 

(c)  The  quantity  of  the  biliary  pigment  may  be  increased  by  injecting  hemo- 
globin into  the  blood  stream. 

{d)  The  deposition  of  iron  in  the  liver  may  be  increased  experimentally  by 
inciting  a  greater  destruction  of  the  red  cells.  This  can  be  done  by  introducing 
toxic  agents  into  the  circulation.  A  disintegration  of  red  cells  also  occurs  under 
pathological  conditions,  for  example,  in  the  course  of  certain  anemias. 

(e)  A  deposition  of  hemoglobin  crystals  in  the  cells  of  this  organ  has  been 
observed. 

(/)  The  blootl  of  the  hepatic  vein  is  said  to  contain  fewer  red  cells  than  that  of 
the  portal  vein. 

{g)  The  endothelial  cells  lining  the  capillaries  of  the  liver,  the  so-called  "Stem- 
zellen,"  possess  the  power  of  taking  up  foreign  particles  and  of  rendering  the  red 
corpuscles  effete. 

A  disintegration  of  the  red  corpuscles  also  occurs  in  the  Ij^mphoid 
tissues  and  in  the  spleen.  This  conclusion  is  based  upon  the  observa- 
tion that  red  cells  or  pieces  of  them  are  found  at  times  in  the  cytoplasm 
of  certain  large  cells,  or  macrophages,  which  are  generally  present  in 

1  Am.  Jour,  of  Physiol.,  xlii,  1917,  256. 
^  Boston  Med.  and  Surg.  Journal,  1892. 


THE    WHITE    BLOOD    CORPUSCLES  199 

these  organs.  It  seems  best,  however,  not  to  attach  too  great  an  im- 
portance to  this  fact,  because  it  can  reachly  be  shown  that  the  spleen 
is  neither  the  only  nor  the  most  important  organ  for  the  destruction  of 
these  elements.  The  evidence  which  tends  to  confirm  this  statement 
is  as  follows: 

(a)  The  removal  of  the  spleen  does  not  seem  to  lessen  the  destruction  of  the 
red  cells,  as  is  evinced  by  the  quantity  of  the  bile-pigment  excreted. 

(b)  If  a  marked  destruction  of  red  corpuscles  actually  did  occur  in  the  spleen, 
the  phagocytic  cells  of  this  organ  should  l)e  loaded  to  their  utmost  capacity  with 
these  cells  or  with  the  substances  derived  from  them.  This  histological  evidence 
has  not  been  supplied  as  yet. 

(c)  Quite  similarly,  the  blood  emerging  from  this  organ  should  show  a  cor- 
puscle count  below  that  of  the  arterial  blood,  and,  furthermore,  should  also  con- 
tain those  bodies  which  are  ordinarily  derived  from  the  red  corpuscles.  That  the 
splenic  blood  undergoes  these  changes  has  not  been  definitely  established. 


CHAPTER  XVII 
THE  WHITE  BLOOD  CORPUSCLES 

PHYSICAL  AND  CHEMICAL  PROPERTIES 

Color,  Shape  and  Size. — The  white  corpuscles  appear  as  small 
globules  of  protoplasm,  measuring  from  4  to  14/x  in  diameter.  Some 
of  them,  therefore,  are  much  larger  and  some  much  smaller  than  the 
red  cells.  Their  substance  is  soft  and  sticky,  grayish  in  color,  homo- 
geneous or  granular,  and  not  surrounded  by  a  clearly  recognizable 
membrane.  Their  surface  is  often  quite  uneven  and  shows  at  times 
irregular  projections  which  break  off  and  float  free  in  the  blood.  Al- 
though these  cells  are  strongly  refracting,  their  nuclear  portion  does 
not  become  sharply  differentiated  until  +hey  have  been  brought  in 
contact  either  with  suitable  stains  or  with  water  and  solutions  of  acetic 
acid.  These  agents  serve  to  contrast  them  more  sharply  against  the 
medium,  because  water  tends  to  render  the  granules  more  conspicuous, 
while  acetic  acid  lessens  the  opacity  of  their  cytoplasm. 

The  Classification  of  the  White  Corpuscles. — The  white  cells  may  be 
arranged  in  groups  in  accordance  with  the  shape  and  size  of  their 
cell-bodies  and  nuclei,  as  well  as  in  accordance  with  certain  differences 
in  the  behavior  of  their  granular  constituents  toward  anilin  dyes. 
Ehrlich^  found  that  some  of  these  granules  react  only  toward  acid 
dyes,  while  others  can  only  be  stained  with  basic  or  neutral  pigments. 
For  this  reason,  the  white  corpuscles  have  been  described  as  acido- 
philes,-  basophiles  and  neutrophiles.  In  accordance  with  their  general 
characteristics,  they  are  divided  into  two  principal  groups  and  these 
again  into  several  others,  as  follows: 

1  Archiv  f.  (Anat.  u.)  Physiol.,  1879,  571,  and  "Die  Anemie,"  1898. 

2  Also  called  oxiphiles  or  eosinophiles. 


200 


THE    BLOOD 


1.  Lymphocytes,  are  not  granular'  and  do  not  show  a  very  pronounced  shifting 
of  their  substance. 

(a)  Small  Type. — These  cells  possess  a  snaall  amount  of  cytoplasm  and  a 
relatively  large  and  symmetrical  nucleus.  They  are  about  as  large  as  the  red 
corpuscles  and  constitute  about  25  per  cent,  of  all  the  white  corpuscles. 

(6)  Large  Type. — These  cells  are  much  larger  than  the  preceding  and  display  a 
broader  margin  of  cytoplasm  around  a  somewhat  eccentric  nucleus.  They  are 
few  in  number  and  often  exhibit  a  granular,  irregularly  stained  network  simu- 
lating true  granulations. 

2.  Leukocytes,  are  granular  and  exhibit  a  very  characteristic  ameboid  motion. 
(a)    Transitional   Type. — These  cells  are  few  in  number   (2  to   10  per  cent.) 

and  contain  a  large  quantity  of  protoplasrh  in  which  a  few  neutrophilic  granules 
are  suspended.  The  nucleus  is  shaped  like  a  horseshoe  or  an  hour-glass,  but  is 
not  divided  into  smaller  masses. 


E  r 

Fig.   109. — Different  Varieties  of  Humax  White  Corpuscles. 
A,  lymphocyte;    B,  mononuclear  leukocyte;   C,  transitional  form;  D,  polynuclear 
leukocyte;  E,  eosinophile  leukocyte;  F,  mast-cell.      (After  Szymonowicz.) 


ih)  Polymorphonuclear  Type. — The  protoplasm  of  these  cells  is  abundant 
and  embraces  many  fine  neutrophile  granules.  The  nucleus  is  lobulated,  its  different 
segments  being  connected  by  strands.  They  form  about  70  per  cent,  of  the  total 
number  of  the  leukocytes.  To  this  group  also  belong  the  eosinophilic  leukocytes 
which,  as  the  name  indicates,  stain  with  acid  dyes,  such  as  eosin.  They  are 
characterized  by  their  coarse  and  strongly  refracting  granules,  and  show  a  most 
active  ameboid  motion. 

(c)  Basophile  Type. — These  cells  are  frequently  called  mast-cells. ^  They  are 
present  in  small  numbers  under  normal  conditions  (less  than  1  per  cent.)  and 
embrace  a  nucleus  consisting  of  two  or  three  segments.  Their  granules  stain 
deeply  with  basic  dyes,  such  as  thionin. 

The  Number  of  the  White  Corpuscles. — It  is  generally  given  as 
6000  to  10,000  per  cu.  mm.,  which  figure  indicates  a  proportion  of  one 
wJiite  to  about  700  red  corpuscles.     The  total  number  of  white  cor- 

1  True  granules  are  present  in  severe  anemias,  but  rarely  in  health. 

2  Discovered  by  Bonders  and  Molischott  in  1848;  also  see:  Hirt,  Dissertation, 
Leipzig,  1855. 


THE    WHITE    BLOOD    CORPUSCLES  201 

piiscles  has  been  estimated  at  19-32,00(),()00,0()0.  They  are  especially 
numerous  in  the  new-born,  counts  of  15,000-19,000  per  cu.  mm.  being 
not  infrequent.  They  become  fewer  in  number  shortly  after  birth, 
but  again  increase  during  infancy,  when  a  value  of  30,000  per  cu.  mm. 
cannot  be  regarded  as  abnormal.  From  the  first  to  the  sixth  year  the 
values  range  between  13,000  and  7000  p(>r  cu.  mm.  A  second  decrease 
takes  place  in  adult  life.  This  is  again  followed  by  an  increase  in 
old  age.  The  ingestion  of  food  rich  in  protein  raises  the  count,  but 
maximal  values  are  not  obtained  until  two  or  three  hours  after  meals. 
Ver}'  pronounced  increases  of  this  character  constitute  the  so-called 
assimilation  or  digestion  leukocytosis.  Fasting  lowers  the  count, 
while  muscular  activity^  and  massage^  raise  it. 

A  transitory  increase  above  the  physiological  maximal  value  is 
designated  as  leukocytosis,  while  a  reduction  below  the  minimal  value 
is  called  hypoleukocytosis  or  leukopenia.  In  accordance  with  the 
data  given  above,  it  is  advisable  to  classify  leukocytosis  as  physio- 
logical and  pathological,  this  division  being  based  solely  upon  the  cause 
of  the  increase.  A  pathological  leukocytosis,  for'  example,  arises  in 
the  course  of  many  febrile  reactions  and  especially  after  hemorrhages 
and  in  consequence  of  suppurative  processes.  It  is  also  possible  to 
produce  this  condition  by  the  administration  of  quinin,  turpentine, 
albumose,  nucleic  acid,  bacterial  products  and  extracts  of  thymus, 
spleen  and  bone-marrow.  A  leukopenia  of  marked  degree  frequently 
follows  exposure  to  the  Rontgen  rays. 

The  method  employed  in  determining  the  number  of  the  leukocytes  is  the 
same  as  that  made  use  of  in  counting  the  red  cells,  but  as  a  larger  drop  of  blood 
is  needed  in  this  case,  the  pipet  and  counting  chamber  must  be  somewhat  larger 
in  size.^  In  order  to  render  the  white  corpuscles  more  conspicuous,  the  red  cor- 
puscles must  first  be  destroyed  by  adding  a  small  quantity  of  acetic  acid  to  the 
diluting  fluid.  It  is  also  possible  to  add  some  coloring  material  to  the  latter  so  that 
the  total  count  may  at  the  same  time  be  amplified  by  a  differential  count.*  In 
general,  however,  it  is  advisable  to  differentiate  these  cells  in  a  stained  smear, 
because  abnormal  forms  of  leukocytes  are  difficult  to  recognize  in  the  counting 
chamber. 

The  Chemical  Composition  of  the  White  Corpuscles. — ^The  direct 
chemical  analysis  of  the  white  corpuscles  meets  with  the  difficulty  that 
it  is  quite  impossible  to  secure  these  cells  in  sufficient  numbers. 
Their  chemical  characteristics,  however,  have  been  studied  in  an 
indirect  way  by  making  use  of  the  so-called  pus-corpuscles  which  are 
always  present  in  tissues  which  have  been  invaded  by  pus-producing 

1  Zuntz,  Physiologie  des  Marsches,  Berlin,  190L 

2  Zangemeister  and  Wagner,  Deutsche  med.  Wochenschr.,  xxviii,  1902,  549. 

^  A  special  counting  cell  has  been  devised  by  Brener  (Berliner  klin.  Wochen- 
schr., xxxix,  1902,  954. 

^  Tiirk   (Wiener  klin.  Wochenschr.,  xv,  1902,  715)  recommends  a  mixture  of: 

Glacial  acetic  acid 3  c.c. 

Distilled  water 300  c.c. 

Gentian  violet,  1  per  cent,  aqueous  solution 2  to  3  c.c. 

Also  see:  ZoUikofer,  Zeitschr.  f.  wissensch.  Mikr.,  xvii,  1900,  313. 


202  THE   BLOOD 

bacteria.  It  is  also  possible  to  obtain  large  numbers  of  lymphocytes 
from  lymphatic  glands.  As  will  be  explained  more  fully  later  on, 
the  pus-corpuscles  are  the  remnants  of  destroyed  leukocytes.  They 
show  a  content  in  water  of  90  per  cent.  The  solids  (10  per  cent.) 
consist  chiefly  of  albumin,  globulin,  nuclein,  nucleoprotcid  and  nucleo- 
histon.  Neutral  fats  appear  in  their  cytoplasm  as  strongly  refracting 
granules,  Cholesterin,  lecithin,  glycogen  and  alkaline  phosphates 
are  also  present. 

The  Origin  and  Fate  of  the  White  Blood  Corpuscles. — 'The  different 
views  regarding  the  formation  of  the  white  corpuscles  may  be  said  to 
advocate  either  a  monophyletic  or  a  dualistic  origin.  In  accordance 
with  the  former,  the  different  varieties  of  white  corpuscles  are  regarded 
as  having  arisen  from  a  single  mother-cell.^  To  be  sure,  the  facts 
favoring  this  unitarian  mode  of  generation  are  insufficient,  at  least 
when  applied  to  the  adult  animal,  but  it  is  also  true  that  the  objections 
commonly  raised  against  it,  lose  much  of  their  weight  when  the  condi- 
tions existing  in  the  embryo  are  more  fully  considered.  The  dualistic 
theory  is  based  upon  the  contention  that  the  lymphocytic  white  cells 
arise  from  the  so-called  lymphoblasts  which  are  present  in  the  adenoid 
tissue  of  the  lymphatic  glands  and  lymph  nodules,  and  that  the  larger 
ameboid  types,  or  leukocytes,  are  descended  from  the  myeloblasts  of 
the  bone-marrow.  This  view,  which  was  first  expressed  by  Ehrlich, 
is  the  most  favored  at  the  present  time. 

The  lymph  nodule  consists  of  a  dark  peripheral  and  a  clear  inner 
zone,  or  germ  center.  The  latter  is  formed  by  large  cells  which 
divide  and  give  rise  to  the  lymphocytes.  The  largest  number  of  these 
then  escape  into  the  lymph  channel  situated  at  the  periphery  of  the 
nodule,  but  a  few  of  them  also  enter  the  blood  stream  directly.  Those 
white  corpuscles  which  originate  in  the  marrow  of  the  bones,  have  as 
their  precursors  the  so-called  myelocytes  which  present  themselves 
as  granular  or  non-granular  protoplasmic  masses  with  rounded  nuclei. 
By  transition  these  elements  finally  assume  the  characteristics  of  the 
leukocytes,  and  eventually  escape  into  the  blood  capillaries  of  the 
marrow,  whence  they  are  distributed  to  all  parts  of  the  body. 

The  duration  of  the  life  of  these  colorless  corpuscles  has  not  been 
determined  with  accuracy.  They  undergo  dissolution  and  disappear. 
Many  of  them  are  destroyed  while  engaged  upon  their  mission  of 
ridding  the  body  of  toxic  substances. 

THE  FUNCTION  OF  THE  WHITE  BLOOD  CORPUSCLES 

Contractility  and  Motion. — A  molecular  movement  of  the  cyto- 
plasm has  been  observed  in  all  white  corpuscles,  but  with  the  exception 
of  the  polynuclear  and  mononuclear  varieties,  this  movement  is  not 
sufficiently  strong  to  cause  motion.  White  cells  may  be  obtained 
without  much  difficulty  by  placing  a  drop  of  blood  upon  a  glass  slide 
1  Weidenreich,  Ergebn.  der  Anat.  und  Entwickelungsgeschichte,  xix,  1911,  2. 


THE    WMITK    lU.OOD    CORPUSCLES    ,  203 

and  romovinp;  from  it  the  nnl  corijusclcis  l)y  moans  of  a  lateral  drainage 
stream  of  slight  force.  The  white  cells  then  stick  to  the  surface  of  the 
slide  and,  if  kept  in  a  warm  isotonic  solution,  may  be  studied  for  some 
time  thereafter.  They  may  also  be  obtained  from  the  frog  by  insert- 
ing a  platelet  of  porous  wood  under  the  skin  covering  the  dorsal  aspect 
of  its  body.  If  permitted  to  remain  in  this  position  for  several 
hours,  the  meshes  of  the  wood  will  be  filled  with  many  leukocytes,  the 
removal  of  which  can  easily  be  effected  by  washings  with  normal  saline 
solution.  They  may  be  studied  in  a  more  plastic  manner  by  placing 
the  frog's  mesentery  or  bladder  under  the  microscope.  In  the  cir- 
culating blood  they  appear  as  translucent  globular  bodies,  which,  on 
account  of  their  lesser  specific  gravity,  leave  the  swift  axial  stream  and 
enter  the  more  slowly  moving  peripheral  layers  of  the  current.  They 
attach  themselves  here  or  there  to  the  vessel  wall,  but  soon  pass  on- 
ward again  b}'  executing  a  peculiar  rotary  motion. 

Under  favorable  conditions  the  leukocytes  exhibit  a  movement 
of  their  cytoplasm^  which  is  very  similar  to  that  displayed  by  the 
ameba.  Their  substance  contracts  and  relaxes  alternately,  while  their 
nuclear  constituents  remain  rather  stationary  and  serve,  so  to  speak, 
as  a  center  for  this  movement.  Prolongations,  commonly  designated 
as  pseudopodia,  are  sent  out  in  different  directions  into  the  surrounding 
medium  to  be  again  retracted  later  on  with  varying  swiftness.-  -Thus, 
a  leukocyte  may  extend  and  retract  its  pseudopodia  repeatedly  without 
altering  its  position,  but  it  may  also  happen  that  one  of  its  prolonga- 
tions becomes  attached  to  the  surface  and  that  the  remaining  mass  of 
the  cell  is  slowly  moved  onward  in  the  direction  of  this  fixed  point. 
This  property  of  the  leukocytes  to  adhere  to  surfaces  is  attributed  by 
Verworn  to  the  extrusion  of  a  mucous  secretion.  When  freely  moving 
they  usually  present  a  globular  outUne  which  impUes  that  they  are  in 
a  state  of  contraction. 

Phagocytosis. — Whether  the  leukocyte  remains  stationary  or 
moves  onward  to  a  different  place,  the  molecular  shifting  of  its  sub- 
stance is  instrumental  in  bringing  it  into  relation  with  various  particles 
of  food  and  other  extraneous  material.  As  is  true  of  other  low  forms 
of  life,  the  leukocyte  behaves  in  a  very  characteristic  manner  toward 
these  substances,  being  either  attracted  or  repelled  by  them.  This 
orientation  is  brought  about  largely  by  chemical  means,  and  hence,  the 
leukocytes  may  be  said  to  possess  the  property  of  chemotropism  or 
chemotaxis  of  a  positive  and  negative  kind. 

The  chemotropic  qualities  of  the  leukocytes  must  beheld  responsible 
for  their  power  of  taking  up  nutritive  particles  and  of  englobing  and 
digesting  all  that  material  which  is  foreign  or  injurious  to  the  body. 

^  First  observed  by  Wharton  Jones  in  1846,  and  proved  for  the  human  leuko- 
cyte by  Davaine  in  1850.  Lieberkiihn  gave  an  adequate  description  of  this 
movement  in  1854. 

2  Verworn,  Pfluger's  Archiv,  li,  1891;  also  see:  Maximow,  Ziegler's  Beitrage, 
Ixxiii,  1909  and  Ixxvi,  1910. 


204  .  THE    BLOOD 

For  this  reason,  they  are  frequently  spoken  of  as  devouring  cells  or 
phagocytes  (to  eat-cell),.and  are  further  characterized  as  the  "police- 
men of  the  blood."  In  illustration  of  their  function  the  following 
phenomenon  may  be  cited:  As  the  larva  of  the  fly  changes  into  the 
mature  insect — a  metamorphosis  which  occurs  rather  rapidly — such 
structures  as  the  creeping  muscles  become  superfluous  and  undergo 
degenerative  changes.  The  substances  which  are  formed  during  this 
catabolic  process,  exert  a  strong  chemotactic  influence  upon  the 
leukocytes  with  the  result  that  this  tissue  soon  becomes  overcrowded 
with  them.  The  ensuing  phagocj^tosis  soon  leads  to  the  removal  of 
these  now  useless  parts.  The  absorption  of  the  tail  of  the  tadpole  is 
accomplished  in  a  similar  manner.  It  is  also  known  that  they  invade 
injured  tissues  and  help  in  the  removal  of  the  superfluous  cellular 
material,  but  whether  they  actually  take  part  in  the  process  of  recon- 
struction, is  still  doubtful.     To  be  sure,  ]\Ietchnikoff  ^  has  expressed 


Fig.   lllJ. — Leukocytes  Exgolfixg  Particles  of  Lndia  Ixk. 

the  idea  that  the  emigrated  leukocytes  undergo  certain  changes  which 
enable  them  to  become  connective-tissue  cells,  but  most  authors 
believe  that  this  regeneration  is  accomplished  solely  by  the  plasma  cells 
of  the  tissues. 

Of  even  greater  importance  and  interest  are  the  phagocytic  quali- 
ties displayed  by  the  leukocytes  when  brought  in  relation  with  patho- 
genic bacteria.  But  while  capable  of  ridding  the  body  of  different 
dead  and  hving  germs,  the  leukocytes  are  not  capable  of  destroying 
all  varieties  of  them.  They  seem  to  be  attracted  especially  by  the 
ordinary  pus  microbes  or  by  the  products  of  their  metabohsm,  which 
fact  is  well  proven  by  an  experiment  described  by  Pfeffer.  A  capillary 
tube,  closed  at  one  end,  is  filled  with  a  culture  of  staphylococcus  pyo- 
genes albus  or  aureus.  It  is  then  placed  under  the  skin  or  into  the 
abdominal  cavity  of  a  rabbit.  On  removing  it  10  to  12  hours  later, 
the  microscopical  examination  reveals  great  numbers  of  leukocytes  in 
the  culture,  actively  engaged  in  ingesting  the  bacteria.  The  fact  that 
the  bacteria,  and  not  the  culture,  are  responsible  for  the  migration  of 
the  leukocytes  into  the  tube,  can  readily  be  proven  by  employing  a 

*  Pathol,  compar.  de  rinflammation,  Paris,  1892. 


THE    WHITE    BLOOD    CORPUSCLES  205 

medium  .containing  no  germs.     Under  this  condition  the  k'ukocytes 
do  not  enter  the  tube. 

Opsonins. — It  was  observed  at  an  early  date  that  the  leukocytes 
behave  at  times  in  a  very  indifferent  manner  toward  certain  types 
of  bacteria,  and  liencc,  it  was  thought  likely  that  these  germs  must 
first  be  killed  liefore  the  phagocytosis  can  take  its  regular  course. 
Metchnikoflf  then  expressed  the  view  that  the  leukocytes  are  capable 
of  surrounding  living  material  under  ordinary  conditions,  but  that 
the  complete  destruction  of  the  latter  necessitates  the  presence  of  a 
specific  intermediary  agent,  ^t  was  assumed,  therefore,  that  the 
fluids  of  the  ])ody  contain  special  activators  which  stimulate  the  leuko- 
cytes  to  greater  activity. 

Leishman^  and  Wright  and  Douglass-  showed  later  on  that  the 
phagocytosis  may  be  greatly  augmented  by  blood  plasma  or  serum 
which   has  been  treated  in  a  particular  way. 
It  could  be  proved  by  the  centrifugalization     ,.v;^'vTr^;-^v, 
of  bacterial  mixtures  that  this  process  tends    ^:^^^^ 
to    diminish    the   reinforcing   power    of   the  •■.";'■ 
serum,    while    the    bacteria   are    ''sensitized  't  s' 
thereby,"  i.e.,  they  are   rendered  especially    ^^^i-i.;.*.--. ■.;.-.;,  .r'^'iv't, 
vulnerable  to  the  leukocytes.     In  this  way,  "?y.".':T--ij  :■;'•■'?' 

it  has  been  established  that  the  bacteria  in-  ff^-^--'  r^^'^i-i'h 

teract  with  certain  specific  bodies  of  the  blood.  jf'^.'  .  'V.'  ".''v^,       /-» 

These  bodies  which,   so  to  speak,  i-ender  the  ^^:;>"'-*y  •'•^'V-- 

bacteria  palatable  to  the  leukocytes,  are  called  ;:i-\  i'-^:s"^?;)'S4 

opsonins  (prepare  for  a  meal).  l^viv' •;:■%''  '% 

The  function  of  the  opsonins,  therefore,  is  '•^■^■'■0. 

to  produce  certain  physicochemical  changes  '^.5;t;-i^:i- 

in  the  substance  of  the  bacteria  so  that  the  '■"••' 

leukocytic  material  is  able  to  react  with  it.    ^' youm^^BlcxE™!^''" 

Pamt     applied     to     Wmdow     glass     will     soon     q,  indicates  part  played  by 

crumble  off,  but  will  stick  to  it  for  an  indefi-  opsonin. 

nite  period  if  the  glass  is  first  eroded  with  a 

fluoride.     The  opsonins  are  comparable  to  the  eroding  fluid.     They 

attack  the  bacterial  substance  and  lessen  its  power  of  resistance  so 

that  the  leukocytic  material  is  able  to  combine  with  it. 

The  resistance  and  immunity  of  an  animal  against  microbic  in- 
fections depends  in  a  measure  upon  the  phagocytic  properties  of  its 
leukocytes.  But  in  order  to  attain  this  power  it  is  necessary  to  have 
at  hand  not  only  a  sufficient  number  of  leukocytes,  but  also  leukocytes 
of  the  proper  quality.  In  addition,  it  is  essential  that  it  be  in  posses- 
sion of  opsonins,  because  without  these  bodies  a  reaction  between  the 
protecting  cells  and  the  invading  bacteria  cannot  always  be  brought 
about.     Conversely,  it  is  true  that  a  large  content  in  opsonins  cannot 

1  British  Med.  Jour.,  Ixxiii,  1902. 

^  Proc.  Royal  Soc,  London.  Ixxii,  1904.  A  brief  discussion  of  opsonins  has 
been  given  by  Hektoen,  in  Science,  Februarj-  12,  1909. 


206 


THE    BLOOD 


serve  as  an  adequate  protection  if  the  leukocytes  are  inferior  in  num- 
ber or  power.  The  best  results  can  only  be  obtained  if  these  two 
factors  are  properly  balanced.  The  opsonin  content  may  be  deter- 
mined experimentally,  the  result  being  the  so-called  opsonin-indcx  of 
the  body.  By  treating  an  animal  in  a  specific  way,  the  number  of  its 
leukocytes  and  opsonin-content  may  be  increased  so  that  its  power  of 
resistance  becomes  much  greater  than  ever  before. 

Diapedesis. — ^This  term  was  originally  applied  to  the  passage  of 
the  blood  or  of  its  formed  elements,  chiefly  the  red  cells,  through  the 
wall  of  a  blood-vessel.  Cohnheim,  however,  has  shown  in  1869  that 
this  power  of  migration  into  the  neighboring  tissues  is  a  distinct 
characteristic  of  the  leukocytes.  In  contradistinction  to  the  passive 
behavior  of  the  red  corpuscles,  the  latter  are  aided 
in  their  escape  from  the  vascular  system  by  their 
ameboid  properties.  A  delicate  pseudopodium  is 
first  protruded  through  a  perforation  in  the  vessel 
wall,  after  which  the  principal  mass  of  the  cell  is 
slowly  drawn  through  the  opening  until  entirely 
outside  the  vascular  channel.  An  assemblage  of 
great  numbers  of  these  corpuscles  outside  the  main 
circulatory  system  results  whenever  a  tissue  has 
been  injured  or  has  become  the  seat  of  an  infective 
process.^  Under  these  circumstances,  their  migra- 
tion is  greatly  facilitated  by  certain  changes  in  the 
flow  of  the  blood,  namely: 

(a)  A  relaxation  of  the  capillaries  in  the  area  affected 
so  that  the  size  of  the  blood-bed  becomes  larger;  (b)  an 
accumulation  of  a  larger  quantity  of  blood  in  this  par- 
ticular region  which  tends  to  produce  a  local  rise  in  tem- 
FiG.  112. — DiAPEDE-  perature;  and  (c)  a  diminution  in  the  velocity  of  the  blood 
SIS  OF  Leukocytes,  flg^  which  enables  the  white  corpuscles  to  assemble  in 
numbers  and  to  attach  themselves  more  securely  to  the 
vessel  wall.  These  dynamical  changes  indicating  an  inflammatory  reaction, 
may  be  studied  under  the  microscope  in  such  tissues  as  the  mesentery,  tongue, 
lung  or  web  of  the  frog,  if  they  are  first  moistened  with  normal  saline  to  which  a 
few  drops  of  alcohol  or  a  small  amount  of  mustard  has  been  added. 

Having  invaded  the  tissue,  the  leukocytes  immediately  display  their 
phagocytic  properties.  Supposing  that  the  inflammatory  reaction  has 
been  produced  by  bacteria,  the  outcome  of  this  interaction  depends 
upon  the  relative  strengths  of  the  leukocytes  and  invading  cell.  If 
the  latter  is  the  more  powerful  factor,  the  infection  will  gradually 
extend  to  neighboring  areas  of  the  tissue,  while  if  the  former  is  the 
stronger,  the  bacteria  will  eventually  be  encircled  and  eliminated. 
But,  in  either  case,  large  numbers  of  leukocytes  will  be  destroyed  in 
the  course  of  this  process,  their  remnants  appearing  in  the  extrava- 
sation  in    the    form    of    pus-corpuscles.     The    foregoing   discussion 


^Adami,   Inflammation,   Macmillan,  New  York,  1909. 


THE    BLOOD    PLATELETS  207 

clearly  shows  that  the  leukocytes  constitute;  a  most  important  safe- 
guard against  bacterial  invasion.  They  are  therefore  directly  con- 
cerned with  the  pro<hiction  of  immunity. 

In  this  conncM'tion  nuuition  should  also  l)C  made  of  the  fact  that  the 
mammalian  body  contains  other  types  of  phagocytes  to  which  differ- 
ent names  have  been  given.  Contrary  to  the  white  corpuscles, 
which  are  migratory  phagocytic  entities,  the  cells  now  referred  to 
remain  "stationary."  They  are  found,  for  exami)lc,  in  bony  tissue 
where  they  have  to  do  with  the  absorption  and  removal  of  all  super- 
fluous material,  or  in  the  spleen  and  liver  where  they  take  up  the 
worn  out  red  corpuscles  and  destroy  them.  To  the  first  type  of  cells 
belong  the  myeloplaxes  of  the  bone-marrow,  while  the  second  group  is 
represented  by  the  so-called  giant  cells  and  the  third,  by  the  endothelial 
lining  cells  of  the  hepatic  capillaries,  generally  known  as  the  "Stern- 
zellen"  of  Kupfer.  Since  the  aforesaid  cells  are  so  closely  related  in 
function,  it  is  quite  probable  that  they  are  also  allied  to  the  leuko- 
cytes in  structure  as  well  as  embryologically. 

Allied  Functions. — Certain  other  functions  have  been  ascribed  to 
the  white  corpuscles,  the  most  important  of  which  is  their  power  of 
taking  up  nutritive  material  and  of  carrying  it  to  different  parts  of  the 
body.  Thus,  the  lymphoc3^tes  are  said  to  absorb  fat  globules  and  to 
convey  them  into  the  lymph  channels.  They  are  also  supposed  to 
aid  in  the  absorption  of  the  peptones  and  to  help  in  maintaining  a 
proper  protein  content  of  the  blood.  Both  functions  are  in  keeping 
with  their  phagocytic  properties.  Sufficient  evidence  is  also  at  hand 
to  show  that  the  leukocytes  contain  a  substance  which,  when  liberated, 
plays  an  important  part  in  the  coagulation  of  the  blood. 


CHAPTER  XVIII 

THE  BLOOD  PLATELETS 

Physical  Characteristics. — While  the  blood  platelets  are  usually 
described  as  rounded  biconvex  discs,  it  must  be  granted  that  their 
shape  varies  considerably  from  ahnost  globular  to  flat.  They  have 
also  been  observed  to  assume  a  spindle  shape;  in  fact,  it  is  stated  that 
they  possess  this  form  normally  in  the  horse.  They  give  no  particu- 
lar color  impression.  Their  granular  centers  refract  very  strongly, 
and  stain  deeply  with  basic  dyes.  For  this  reason,  they  are  said  to 
contain  a  real  nucleus,  and  may  therefore  be  regarded  as  true  cells. 
They  display  ameboid  movements,  and  if  collected  in  a  favorable 
medium,  present  a  number  of  variegated  processes.  Their  specific  grav- 
ity is  less  than  that  of  the  other  formed  elements  of  the  blood,  which 
fact  accounts  for  their  occupying  the  outermost  layers  of  the  blood 
stream.     As  their  diameter  measures  as  a  rule  no  more  than  3/i,  they 


208 


THE    BLOOD 


are  scarcely  half  as  large  as  the  red  corpuscles,  but  cells  considerably 
larger  or  smaller  than  these  are  not  uncommon.  Their  number  is 
usually  given  as  180,000  to  800,000  per  cu.  mm.,  which  means  that  they 
are  more  numerous  than  the  leukocytes. 

Methods  of  Examination. — A  few  platelets  can  always  be  secured 
by  carefully  collecting  a  drop  of  blood  in  normal  saline  solution;  much 
better  results,  however,  are  obtained  with  Haymen's  fluid.  ^  Bizzozero^ 
recommends  a  solution  of  30  per  cent,  gentian  violet  in  a  0.75  per  cent, 
sodium  chlorid  solution.  Their  immediate  fixation  may  be  achieved 
by  drawing  the  blood  into  a  1  per  cent,  solution  of  osmic  acid,  or  better 
still,  bj"  previously  moistening  the  tip  of  the  finger  from  which  the 
blood  is  to  be  taken  with  this  solution.^  Deetjen  preserves  them  by 
permitting  a  droplet  of  blood  to  flow  upon  agar  jelly.*     By  making  use 

of  their  slight  specific  gravity,  Biirker^  sepa- 
rates them  from  the  other  formed  elements  in 
the  following  manner.  A  drop  of  blood  is 
collected  upon  a  thin  sheet  of  paraffin  and  is 
allowed  to  stand  for  a  short  time.  The  lighter 
platelets  collect  near  the  surface  of  the  drop 
and  may  be  removed  by  drawing  a  cover-glass 
through  its  upper  layers. 

Origin  and  Fate  of  the  Blood  Platelets. — 
Haymen,  their  discoverer,  regarded  the  throm- 
bocytes as  carriers  of  hemoglobin  and  there- 
fore as  transitional  types  of  the  red  corpuscles. 
He  designated  them  as  hematoblasts.  Bizzo- 
zero,  on  the  other  hand,  first  expressed  the 
view  that  they  are  independent  elements  and 
are  therefore  neither  embryonic  red  cells  nor  the  remnants  of  destroyed 
corpuscles.  To  be  sure,  fragmented  red  cells  may  appear  in  the  blood 
at  times,  but  a  diiTerentiation  between  these  bodies  and  the  blood 
platelets,  as  described  by  Bizzozero,  is  readily  possible  upon  the  basis 
of  their  histological  characteristics.  The  supposition  that  the  throm- 
bocytes are  fragmentary  white  corpuscles  also  lacks  satisfactory  con- 
firmation. Thus,  it  is  a  well-known  fact  that  the  latter  do  not  dis- 
integrate in  great  numbers  in  the  circulating  blood  and  neither  do 
they  break  up  with  undue  rapidity  in  shed  blood.  It  may  indeed 
be  concluded  that  they  are  relatively  resistant,  because  they  are  often 
preserved  in  extravascular  and  intravascular  coagula  of  long  standing. 
The  conclusion,  that  the  thrombocytes  are  not  derived  from  the 

1  Archives  de  physiol.  norm,  et  pathol.,  x,  1878. 

2  Virchow's  Arch,  fiir  path.  Anat.,  xc,  1882. 

'  Kemp,  Stud.,  Biol.  Lab.,  J.  Hopkins  Univ.,  iii,  1886. 

*  Made  by  dissolving  5  gr.  of  agar-agar  in  500  c.c.  of  distilled  water.  To  100 
c.c.  of  the  filtrate  are  added  0.6  gr.  NaCl  solution,  6  to  8  c.c.  of  a  10  per  cent. 
NaPOa  solution  and  5  c.c.  of  a  10  per  cent.  K2HPO4  solution.  See:  Deetjen,  Vir- 
chow's Archiv,  clxiv,  1901,  260. 

5  Pfluger's  Archiv,  cii,   1904,  36. 


Fig.  113. — Thrombocytes 
Highly  Magnified. 


THE  COAGULATION  OF  THE  BLOOD  209 

other  formed  elements  of  the  blood,  makes  it  necessary  to  examine 
the  evidence  pertaining  to  their  origin  somewhat  more  closely.  It 
is  believed  (a)  that  they  are  not  present  in  the  normal  circulating  blood, 
and  appear  only  if  the  latter  is  brought  in  contact  with  a  foreign  body, 
and  (6)  that  they  are  preexisting  and  constant  constituents  of  the 
blood.  The  former  view  contends  that  the  thrombocytes  do  not  be- 
long to  the  class  of  the  formed  elements,  but  appear  together  with 
those  chemicophysical  alterations  which  indicate  the  beginning  of  the 
coagulation  of  the  blood.  They  constitute,  so  to  speak,  condensation 
or  precipitation  products  of  the  globulin  constituents  of  the  blood. 
This  view^  has  found  support  in  the  following  observations.  It  is 
true  that  the  platelets  are  absent  from  the  blood  of  several  animals, 
for  example,  from  that  of  the  frog,  fishes  and  birds.  It  is  also  conceded 
that  they  are  not  very  conspicuous  in  the  blood  of  several  mammals, 
but  may  be  rendered  more  prominent  in  these  animals  by  first  injuring 
the  wall  of  one  of  their  blood-vessels  or  by  introducing  a  foreign  body 
into  their  circulatory  system.  Under  these  conditions  they  may  be 
seen  to  collect  upon  the  injured  area  in  the  form  of  a  deposit.  More- 
over, Buckmaster  has  shown  that  blood  drawn  into  the  sterile  serum 
of  another  animal,  does  not  always  display  these  bodies,  but  exhibits 
them  very  promptly  if  it  is  collected  in  the  loop  of  a  platinum  wire. 
Furthermore,  while  they  are  not  present  in  fresh  plasma  which  has 
been  rendered  non-coagulable  by  sodium  oxalate  or  peptone,  they  ap- 
pear in  this  plasma  in  large  numbers  after  it  has  been  cooled  for  a 
period  of  about  24  hours.  Lastly,  blood  which  has  been  treated  with 
an  anticoagulating  agent  while  still  in  the  circulatory  system,  does 
not  show  them,  nor  do  they  appear  in  it  later  on  after  its  withdrawal 
from  the  body. 

The  evidence  which  may  be  submitted  in  favor  of  the  second  view, 
advocating  the  preexistence  and  independency  of  the  thrombocytes, 
is  as  follows:  Quite  aside  from  the  fact  that  we  are  in  possession  of 
definite  methods  for  their  isolation,  we  possess  in  the  mesentery  of  the 
guinea-pig  and  in  the  wings  of  the  bat  preparations  in  which  it  is  possi- 
ble to  observe  them  directly.  Moreover,  they  are  present  in  large 
numbers  in  the  blood-vessels  of  the  subcutaneous  connective  tissue  of 
various  animals  and  particularly  in  that  of  the  new-born  rat.  If  to 
these  facts  are  added  the  observations  regarding  their  ameboid 
motion,^  as  well  as  certain  observations  pertaining  to  their  physical 
and  chemical  characteristics,  such  as  their  stickiness,  their  great  vul- 
nerability and  their  very  manifest  power  to  incite  the  coagulation  of 
the  blood, ^  it  cannot  be  doubted  that  they  are  preformed  and  function- 
ally distinct  constituents  of  the  blood. 

1  Wooldridge,  Die  Gerinnung  des  Blutes,  Veit  and  Co.,  Leipzig,  1894,  and 
Loswit,  Virchow's  Archiv  fiir  path.  Anat.,  cxvii,  1889. 

^Deetjen:  Virchow's  Archiv  fiir  path.  Anat.,  cxlvi,  1901,  and  Deckhuysen, 
Anatom.  Anzeiger,  xix,  1901. 

3  Eberth  and  Schimmelbusch,  Die  Thrombose,  Stuttgart,  1888,  and  Klopsch, 
Anat.  Anzeiger,  xix,  1901. 

14 


210  THE    BLOOD 

The  red  and  white  corpuscles  having  been  excluded  as  possible 
sources  of  the  thrombocytes,  their  origin  remains  much  in  the  dark. 
Wright,  however,  has  suggested  that  they  arise  from  the  cytoplasm 
of  the  giant  cells,  the  so-called  megakaryocytes,  which  are  found  in 
the  marrow  of  the  bones.  It  is  beheved  that  these  cells  send  out 
pseudopodia  which  become  detached  and  are  carried  away  in  the  blood- 
stream. The  observations  of  E|uke^  and  others  tend  to  show  that  the 
life  of  the  thrombocytes  is  very  short. 

When  the  blood  is  shed,  the  platelets  quickly  agglutinate,  forming 
globular  or  irregular  masses.  Their  formerly  pointed  processes  be- 
come stubby  and  break  off,  while  their  central  portions  swell  up  and 
rupture.  Eventually,  therefore,  the  platelets  are  reduced  to  chips 
of  insignificant  size,  many  of  which  soon  disappear  altogether  by  dis- 
solution, but  the  regions  in  which  the  thrombocytes  have  undergone 
this  disintegration,  soon  become  the  seats  of  active  fibrin-prohferation. 
In  this  way  definite  centers  of  coagulation  are  formed,  from  which  the 
different  shreds  of  fibrin  gradually  extend  through  the  blood  in  all 
directions.  Practically  all  the  platelets  take  part  in  this  process  so 
that  they  finally  become  intricate  constituents  of  the  network  of  fibrin. 
The  red  and  white  corpuscles,  on  the  other  hand,  remain  normal, 
because  the  shreds  of  fibrin  pass  by  them  without  actually  imbibing 
them.  It  has  been  proven  by  Blirker-  that  the  number  of  the  throm- 
bocytes is  proportional  to  the  mass  of  the  fibrin  formed,  and  that  this 
reaction  may  be  varied  by  changes  in  temperature  as  well  as  by  the 
addition  of  chemicals.  Thus,  any  agent  tending  to  cause  a  destruc- 
tion of  the  thrombocytes,  also  hastens  the  coagulation  of  the  blood, 
while  any  substance  possessing  preservative  quahties,  not  only  retards 
this  process,  but  actually  prevents  it.  The  latter  end  may  be  attained 
very  readily  by  the  addition  of  hirudin,^  because  this  substance  pre- 
serves the  thrombocytes.  It  must  be  conceded,  therefore,  that,  quite 
irrespective  of  the  red  and  white  corpuscles,  the  disintegration  of  the 
platelets  gives  rise  to  an  agent  which  plays  a  most  important  part  in 
the  coagulation  of  the  blood.  This  activating  substance  is  designated 
as  thrombokinase. 

1  Jour,  of  the  Amer.  Med.  Assoc,  Iv,  1910. 
-  Pfliiger's  Archiv,  cii,  1904,  36. 

3  A  crystallized  form  of  the  extract  of  leeches.  The  heads  of  these  animals 
contain  the  active  principle,  an  albuminous  body. 


THE    COAGULATION    OF   THE   BLOOD 


211 


CHAPTER  XIX 

THE  COAGULATION  OF  THE  BLOOD 

A.  EXTRA VASCULAR  CLOTTING 

Physical  Changes  in  Coagulating  Blood. — Possibly  the  most  strik- 
ing characteristic  of  the  niaininalian  blood  is  its  power  of  changing  its 
fluid  state  into  one  of  semisolidity.  As  this  conversion,  designated  as 
coagulation,  may  set  in  either  after  the  blood  has  escaped  from  the 
blood-vessels,  or  while  still  within  them,  two  forms  of  clotting  are 
obtained,  namely,  the  extravascular  and  the  intravascular. 


(  \ 


Fig.   114. — The  Coagulation  of  the  Blood. 
A,  Normal  blood;  B,  the  formation  of  fibrin  from  colonies  of  thrombocytes  enveloj)- 
ing  the  formed  elements;  (\  the  separation  into  the  coagulum  and  supernatant  serum. 

In  normal  blood  the  different  corpuscular  elements  are  freely  sus- 
pended in  the  plasma.  When  coagulation  sets  in,  delicate  shreds  of 
fibrin  are  formed  which  advance  from  certain  fixed  points  and  traverse 
the  blood  in  different  directions,  encircling  large  colonies  of  corpuscles. 
In  accordance  with  the  view  of  Wooldridge,  these  filaments  arise  in 
consequence  of  a  deposition  of  fine  crystals  which  become  confluent  and 
are  finally  united  into  an  extensive  network.  The  production  of  fibrin, 
therefore,  is  essentially  a  process  of  crystallization,  so  that  the  coagula- 
tion of  the  blood  may  be  said  to  be  based  upon  the  crystallization  of 
fibrin  from  a  supersaturated  solution.  The  physical  characteristics 
of  these  crystals,  as  well  as  their  functional  properties,  make  it  certain 
that  they  are  retained  in  a  liquid  state  and  should  therefore  not  be 
considered  as  solids.  The  meshes  of  this  network  are  gradually  drawn 
more  closely  together  so  that  the  corpuscular  elements  become  more 
tightly  packed.  The  entire  mass  finally  gravitates  to  the  bottom  of 
the  receptacle.  This  gelatinous  deposit  is  known  as  the  coagulum. 
It  is  composed  of  fibrin,  the  different  types  of  corpuscles,  and  nutritive 
material. 

If  the  blood  is  permitted  to  clot  slowly,  so  that  a  complete  deposi- 
tion of  the  red  cells  is  had,  the  coagulum  presents  a  marginal  zone. 


212 


THE    BLOOD 


the  color  of  which  varies  between  yellowish  gray  and  reddish  gray. 
It  is  composed  in  the  main  of  fibrin  and  colorless  corpuscles  and  seems 
to  originate  in  any  blood  in  consequence  of  certain  peculiarities  in 
its  manner  of  coagulating.  The  name  of  "buffy  coat"  or  crusta 
inflammatoria,  has  been  applied  to  this  region. 

The  hquid  which  separates  from  the  clot  in  constantly  increasing 
quantity,  is  known  as  the  serum.  "WTiile  its  immediate  source  is  the 
plasma,  it  differs  from  it  materially,  because  it  contains  no  corpuscular 
nor  larger  nutritive  elements.  The  separation  of  the  blood  into  the 
clot  and  the  serum  begins  as  soon  as  coagulation  sets  in,  but  is  not 
completed  as  a  rule  until  about  24  hours  later.     During  this  time  the 


Figs.    115    axd    116. — The   Fibrix  Needles   Formed   ix  the  Clottikg  of  Blood. 

PLASNL'i.    OF    Ox.A.L-\TED    Dog's    BlOOD    ClOTTED   BT    THROMBIN.       ThE    PHOTOGRAPHS  ShOW 

the  Needles  as  Seex  With  the  Ultramicroscope. 

A,  photographed  by  sun-light;  B,  by  arc-light.  Only  the  needles  h-ing  in  the  focal 
plane  are  seen  distinctly.     (Hoicell.) 

fibrin  shreds  contract  more  and  more  and  squeeze  additional  amounts 
of  serum  out  of  the  clot.  If  the  vessel  into  which  the  blood  is  with- 
drawn is  kept  in  a  cool  place  and  is  not  disturbed,  the  serum  separates 
as  a  clear,  straw-colored  fluid.  It  frequently  happens,  however,  that 
the  clot  adheres  to  the  walls  of  the  receptacle  and  is  torn,  releasing 
varying  numbers  of  red  and  white  corpuscles.  The  serum  then 
assumes  a  reddish  color  and  acquires  a  specific  gravity  which  is 
much  greater  than  that  of  clear  serum. 

Chemical  Changes  in  Coagulating  Blood. — 'VMiile  the  final  and  most 
important  change  effected  during  coagulation  is  the  formation  of  fibrin, 
this  body  cannot  be  obtained  unless  several  preliminarv  reactions  have 
first  been  completed.     Indeed,  the  process  of  clotting  may  be  divided 


THE  COAGULATION  OF  THE  BLOOD 


213 


into  two  stages,  the  first  ending  with  the  formation  of  thrombin  and 
the  second  with  the  production  of  fibrin.  Fibrin  as  su(!h  is  not  present 
in  the  circulating  blood,  but  is  derived  from  a  precursor  through  the 
intervention  of  thrombin.  The  substance  from  which  fibrin  arises,  is 
known  as  fibrinogen  and  is  present  as  such  in  the  plasmatic  portion  of 
normal  blood.  Fibrinogen,  however,  is  an  inert  body  and  must  first 
be  activated  before  its  conversion  into  the  final  product,  fibrin,  can  be 
achieved.  This  activation  is  made  possible  solely  with  the  help  of  a 
fibrin  "ferment,"  commonly  designated  as  thrombin. 

Thrombin  as  such  is  not  present  in  normal  blood,  but  is  formed  from 
an  inactive  precursor,  called  thrombogen  or  prothrombin.  The  con- 
version of  the  latter  into  its  active  form  is  accomplished  by  means  of 
an  organic  thromboplastic  agent,  called  thrombokinase,  in  the  pres- 
ence of  solul)le  calcium.  The  kinase  is  furnished  by  the  cellular 
elements  of  the  blood,  principally  the  thrombocytes.  To  recapitu- 
late, the  circulating  blood  contains  fibrinogen,  thrombogen  and  solu- 
ble calcium  salts.  If  the  blood  is  brought  in  contact  with  a  foreign 
body  so  that  a  destruction  of  the  thrombocytes  results,  thrombokinase 
is  hberated  which,  with  the  help  of  ionic  calcium,  activates  the  throm- 
bogen into  thrombin.  This  process  constitutes  the  first  phase  of 
coagulation.  Its  completion  in  turn  insures  the  second  phase  which 
consists  in  the  conversion  of  fibrinogen  into  fibrin. 

Blood 


Plasma 


Fibrinogen       Thrombogen  Calcium 


I 


Solids 
(Thrombocytes) 


Thrombokinase 


♦Thrombin<- 


>Fibrin<- 


This  explanation  of  the  process  of  clotting  is  in  accordance  with 
the  views  expressed  by  Moravitz,^  Fuld  and  Spiro,^  and  is  based  upon 
data  which  have  been  furnished  in  large  part  by  Schmidt,  Wooldridge, 
Pekelharing,  and  Hammarsten.  While  this  view  is  open  to  several 
objections,  especially  in  regard  to  the  action  of  thrombin,  it  is  the  one 
commonly  accepted  to-day.     A  second  explanation,  which  is  in  part 

1  Hofmeister's  Beitrage,  iv,  1903,  381;  also  see:  A.  Schmidt,  Zur  Blutlehre, 
Leipzig,  1892  and  Wiesbaden,  1895. 

2  Ibid.,  V,  1904,  171. 


214  THE    BLOOD 

dependent  upon  the  work  of  Wooldridge  and  others,  has  recently  been 
advocated  by  Nolf ^  and  Howell.^  It  is  held  that  prothrombin  may  be 
changed  into  thrombin  by  means  of  calcimn  alone,  but  this  reaction 
is  prevented  ordinarily  by  an  antithrombin^  which  is  always  present 
in  the  blood.  If  the  blood  is  injured,  a  thromboplastic  substance  is 
liberated  by  the  corpuscles  (platelets),  which  neutralizes  the  action  of 
the  antithrombin  and  allows  the  activation  of  the  prothrombin  by  the 
calcium.  The  second  stage  of  coagulation  takes  place  as  described 
previously.  The  theories  just  outlined,  therefore,  differ  only  in 
regard  to  the  action  of  the  "kinase"  which,  on  the  one  hand,  is  said  to 
act  as  a  ferment  which  actually  takes  part  in  the  activation  of  the  pro- 
thrombin, and,  on  the  other,  is  believed  to  inhibit  the  anticoagulating 
substance  so  that  the  calcium  is  able  to  incite  the  reaction. 

Thrombokinase. — As  it  has  not  been  possible  so  far  to  demonstrate  an  organic 
kinase  in  the  plasma  of  the  blood,  it  is  commonly  held  that  this  clotting  agent  is 
contained  in  the  formed  elements.  For  this  reason,  a  disintegration  of  the  latter 
must  necessarily  precede  the  liberation  of  this  substance,  but  as  relatively  few  red 
cells  are  destroyed  during  the  shedding  of  the  blood,  it  may  be  concluded  that 
these  elements  cannot  possibly  harbor  the  coagulating  agent.  It  has  also  been 
observed  that  these  cells  are  quite  ineffective  under  ordinary  conditions,  but 
may  be  changed  into  a  coagulating  agent  if  the  hemoglobin  is  thoroughly  separated 
from  the  stroma.  With  the  help  of  the  latter  even  intravascular  clotting  can 
readily  be  effected.  Practically  the  same  statement  may  be  made  regarding  the 
white  corpuscles.  It  is  true,  however,  that  under  experimental  conditions  clot- 
ting may  be  greatly  accelerated  by  the  addition  of  leukocytic  material.  But  this 
fact  cannot  be  employed  as  a  strong  argument  in  favor  of  the  view  that  they  do 
play  a  part  in  normal  clotting,  because  they  are  found  in  large  numbers  in  exudates 
in  which  coagulation  has  not  taken  place.  And  furthermore,  plasma  from  which 
the  leukocytes  and  red  cells  have  been  removed  by  centrifugalization,  may  be  made 
to  clot  by  the  addition  of  water  or  by  passing  a  current  of  carbon  dioxid  through  it. 
Wooldridge,  moreover,  has  shown  that  the  white  cells  of  lymph,  when  washed  in 
salt  solution,  are  quite  unable  to  clot  the  lymph  from  which  they  have  been  taken 
and  neither  can  they  coagulate  peptone-plasma  in  the  absence  of  platelets  or  their 
derivatives. 

The  thrombocytes,  on  the  contrary,  have  been  shown  to  exert  a  most  important 
influence  upon  coagulation,  because  they  disintegrate  very  rapidly  in  shed  blood 
and  the  amount  of  fibrin  formed  is  nearly  proportional  to  the  number  of  platelets 
destroyed.  Various  experiments  may  be  cited  in  support  of  this  statement. 
Thus,  it  is  possible  to  increase  or  to  decrease  their  destruction  by  subjecting  them 
to  different  temperatures  or  to  different  mechanical  and  chemical  influences. 
In  general,  it  holds  true  that  a  medium  which  tends  to  preserve  them,  delays  the 
coagulation,  while  a  medium  which  is  injurious  to  them,  hastens  this  process. 
For  example,  if  a  drop  of  a  solution  of  ammonium  oxalate  (1/100  N)  is  added  to  a 
drop  of  blood,  coagulation  fails  to  take  place.  If  this  sample  of  blood  is  examined 
later  on,  it  will  be  found  to  contain  the  thrombocytes  in  a  state  of  perfect  preserva- 
tion, while  the  red  and  white  corpuscles  are  thoroughly  fragmented.  Moreover, 
Schmidt  has  called  attention  to  the  fact  that  the  plasma  derived  from  sedimented 
horse-blood,  exhibits  a  difference  in  its  coagulability  in  so  far  as  its  upper  portion 
clots  more  readily  than  its  lower,  but  may  be  made  to  remain  fluid  for  a  much 
longer  time  than  the  latter  by  passing  it  through  a  filter.     In  explanation  of  this 

1  Archives  intern,  de  physiol.,  ix,  1910,  407. 

2  Am.  Jour,  of  Physiol.,  xxix,  1911,  29. 
2  Called  hepatothrombin  by  Nolf . 


THE  COAGULATION  OF  THE  BLOOD  215 

phenomenon,  it  may  be  stated  that  the  thrombocytes,  on  account  of  their  lesser 
specific  gravity,  collect  in  much  greater  numbers  near  the  surface  of  the  plasma  and 
that  they  may  then  be  removed  from  it  by  filtration.  Bizzozero  beat  freshly 
drawn  blood  with  cotton  threads  until  they  were  thoroughly  covered  with  plate- 
lets. They  were  then  washed  in  a  0.7  per  cent,  soluticm  of  sodium  chlorid  to 
remove  the  red  corpuscles.  If  desired,  a  rapid  coagulation  of  artificial  pro- 
thrombin could  then  be  effected  by  suspending  these  threads  in  solutions  of  this 
substance.  To  prove  Ids  point  more  conclusively,  he  showed  subsequently  that 
this  result  cannot  be  ol)tained  with  the  cotton  threads  alone,  while  threads  covered 
with  retl  cells  or  with  leukocytes,  gave  rise,  at  best,  to  only  a  very  slow  type  of 
coagulation.  Moreover,  it  has  been  observed  repeatedly  that  the  disintegrating 
thrombocytes  act  as  centers  for  the  formation  of  fibrin,  and  that  the  injection  of 
platelets  into  the  circulation  produces  intravascular  clotting.  It  must  be  con- 
cluded, therefore,  that  the  platelets  yield  a  substance  which  serves  as  the  exciting 
agent  of  the  coagulation. 

Morawitz  calls  this  agent  thrombokinase,  but  it  is  also  referred  to  as  cytocym. 
If  it  is  assumed  that  the  platelets  are  not  real  cells  but  merely  fluid  crystals,  the 
liberation  of  the  thrombokinase  would  correspond  to  the  deposition  of  these 
crystals  as  insoluble  threads  of  fibrin.  For  the  present,  however,  it  seems  best  to 
adhere  to  the  view  of  Morawitz,  Fuld  and  Spiro  as  previously  outlined.  In 
accordance  with  this  explanation,  it  becomes  necessary  to  assume  further  that  the 
blood  of  those  animals  which  does  not  clot  when  collected  directly  from  the  blood- 
vessel, contains  no  thrombokinase.  The  absence  of  this  agent  is  readily  accounted 
for,  because  these  animals  are  not  in  possession  of  thrombocytes.  Instead, 
their  tissues  contain  a  very  effective  thromboplastic  substance  which  takes  the 
place  of  thrombokinase  and  which  is  brought  in  contact  with  the  blood  as  it 
flows  across  the  opened  surface.  But,  the  mere  fact  that  in  us  and  allied  animals 
the  principal  coagulating  agent  is  held  in  the  blood  itself,  does  not  preclude  the 
possibility  of  a  similar  substance  being  present  in  our  tissues;  in  fact,  it  seems 
entirely  probable  that  we  are  thus  doubly  protected. 

Thrombogen  is  a  normal  constituent  of  the  plasma.  Only  a  part  of  it  is  used 
up  during  coagulation.  The  remaining  portion  escapes  activation  either  because  a 
sufficient  quantity  of  thromboplastic  material  to  cause  its  complete  conversion  is 
not  at  hand,  or  because  its  formation  is  stopped  as  soon  as  the  coagulation  has 
advanced  to  a  certain  stage.  It  is  not  present  in  the  tissues,  and  the  indications 
are  that  it  is  not  derived  from  the  cellular  elements  of  the  blood,  but  is  held  in 
solution  in  the  plasma.  Drinker^  believes  that  it  arises  in  the  bone-marrow, 
because  it  may  be  removed  from  the  latter  in  considerable  amounts  by  perfusion. 
It  is  very  stable  and  is  capable  of  withstanding  the  temperature  of  boiling  water 
for  a  brief  period  of  time.  Although  calcium  is  necessary  to  incite  its  conversion 
into  thrombin,  this  salt  is  by  no  means  the  precursor  of  thrombin.  Thrombogen 
is  also  known  as  prothrombin,  proferment  or  plasmozym. 

Thrombin,  or  fibrin  ferment  is  not  a  preexisting  constituent  of  the  blood  nor 
of  any  one  of  the  fluids  of  the  body.  Thus,  if  blood  is  withdrawn  directly  into  an 
excess  of  alcohol,  the  precipitate,  when  dried,  pulverized,  and  extracted  with 
water,  yields  practically  no  thrombin.  While  it  is  usually  regarded  (Schmidt) 
as  an  enzyme  or  ferment,  it  must  be  remembered  that  an  agent  of  this  kind  possesses 
the  property  of  producing  maximal  reactions  even  when  present  in  minute 
amounts.  Another  peculiarity  of  enzymes  is  their  power  of  producing  a  chemical 
reaction  without  losing  any  of  their  substance.  But  as  Wooldridge,  Nolf  and  Rett- 
ger^  have  failed  to  observe  these  peculiarities  in  thrombin,  its  ferment  nature  has 
not  been  definitely  established.  Indeed,  the  evidence  seems  to  point  rather  the 
other  way,  because  it  has  been  found  that  the  amount  of  thrombin  is  directly  pro- 
portional to  the  amount  of  fibrin  formed,  as  the  following  compilation  will  show: 

^  Am.  Jour,  of  Physiol.,  xli,  1916,  5. 

2  Am.  Jour,  of  Physiology,  xxiv,  1909,  429. 


216  THE    BLOOD 

5  drops  of  thrombin  yield  0.2046  gm.  of  fibrin. 
10  drops  of  thrombin  yield  0.3575  gm.  of  fibrin. 
20  drops  of  thrombin  yield  0.6089  gm.  of  fibrin. 
40  drops  of  thrombin  yield  1.5872  gm.  of  fibrin. 

Besides,  it  has  been  noted  that  thrombin  actually  becomes  a  part  of  the  final 
product,  and  that  this  reaction  does  not  varj^  with  the  temperature,  i.e.,  it  takes 
place  at  17°  C.  as  well  as  at  40°  C.  Rettger,  therefore,  draws  the  conclusion  that 
fibrin  is  not  derived  exclusively  bj'  a  progressive  conversion  of  the  fibrinogen, 
but  may  also  be  produced  by  a  direct  combination  of  these  bodies.  The  product, 
however,  is  unstable,  because  the  thrombin  maj*  be  separated  from  it  with  relative 
ease.  Thrombin  may  also  be  prepared  in  accordance  with  the  directions  given  by 
Schmidt.  1  A  certain  quantity  of  blood  having  been  permitted  to  clot,  the  serum 
is  precipitated  by  the  addition  of  15  to  20  volumes  of  alcohol,  in  excess.  The  pre- 
cipitate is  removed  after  several  days  or  months  and  is  dried,  pulverized  and  ex- 
tracted with  water.  While  this  solution  contains  different  protein  bodies  and  salts, 
it  may  be  concluded  that  the  coagulation  which  it  induces  when  added  to  solutions 
of  pure  fibrinogen,  is  caused  by  its  thrombin  constituent.  Buchanan  and  Gamgee 
advise  to  extract  the  ordinary  washed  fibrin  for  several  days  with  an  8  per  cent, 
solution  of  sodium  chlorid.  The  filtrate  is  not  pure,  but  contains  dissolved 
proteins  in  addition  to  much  thrombin.  Howell-  purifies  this  extract  bj'  shaking 
it  repeatedly  with  chloroform.  In  this  way,  the  coagulable  proteins  are  removed, 
while  the  thrombin  is  left  behind  in  a  pure  state,  although  somewhat  diminished 
in  quantity.  This  author  states  that  it  is  easily  soluble  in  water  and  is  not  coagu- 
lated by  boiling.  Moreover,  while  it  is  difficult  to  precipitate  it  with  alcohol  in 
excess,  it  may  be  precipitated  with  ammonium  sulphate  in  half  saturation.  As 
it  gives  positive  results  with  several  of  the  ordinary  protein  reagents,  it  must  be 
regarded  as  a  protein  substance. 

Fibrinogen  exists  as  an  independent  body  in  the  plasma  of  the  circulating 
blood.  It  is  also  present  in  lymph,  chyle,  and  certain  transudates  and  exudates, 
but  not  in  the  blood  serum,  inasmuch  as  it  is  used  up  in  the  process  of  clotting. 
While  its  place  of  origin  is  not  definitely  known,  it  is  certain  that  it  is  not  derived 
from  the  corpuscular  elements  of  the  blood.  It  should  be  mentioned,  however, 
that  some  evidence  is  at  hand  to  show  that  it  may  be  formed  in  the  liver  and  in  the 
myeloid  tissue  of  the  bone-marrow.  Thus,  Nolf  has  found  that  the  quantity  of 
fibrinogen  in  the  blood  may  be  greatlj'  diminished  by  extirpating  the  former  organ 
or  by  the  administration  of  poisonous  amounts  of  phosphorus  or  chloroform.  Men- 
tion should  also  be  made  of  the  observation  of  Dastre  that  the  blood  of  the  mesen- 
teric vein  is  richer  in  fibrinogen  than  that  of  the  corresponding  artery.  This  fact 
has  been  interpreted  as  showing  that  the  intestinal  wall  is  one  of  the  sources  of 
this  substance. 

Fibrinogen  maj^  be  obtained  in  solution  and  free  from  other  proteins  in  the 
following  manner:  A  quantity  of  fresh  blood  is  mixed  with  a  solution  of  sodium 
oxalate  in  amounts  sufficient  to  give  a  0.1  per  cent,  oxalate  mixture.  The  latter 
is  then  centrifugalized  and  its  plasma  portion  precipitated  by  the  addition  of  an 
equal  amount  of  a  saturated  solution  of  sodium  chlorid.  The  resulting  precipitate 
of  fibrinogen  is  pressed  out  or  centrifugalized,  redissolved  in  an  8  per  cent,  salt 
solution,  and  the  filtrate  precipitated  by  a  saturated  salt  solution.  Having  been 
subjected  to  this  process  three  times,  the  final  precipitate  is  pressed  between  filter 
paper  and  is  then  finely  divided  in  water.  The  precipitate  ma}'  be  dissolved 
in  a  1  per  cent,  solution  of  sodium  chlorid.  If  it  does  not  dissolve  readily,  a  few 
drops  of  a  0.5  per  cent,  solution  of  sodivim  bicarbonate  should  be  added.  The 
traces  of  sodium  oxalate  may  be  removed  by  diah'sis  in  a  colloidin  sac,  against  a 
1  per  cent,  solution  of  sodium  chlorid. 

1  Pfliiger's  Archiv,  xi,  1887,  515. 

2  Am.  Jour,  of  Physiol.,  xxvi,  1910,  26. 


THE  COAGULATION  OF  THE  BLOOD  217 

A  pure  solution  of  fibrinogen  may  be  kept  at  ordinary  temperatures  for  an 
indefinte  period  of  time  without  its  yielding  even  traces  of  fibrin.  A  perfectly 
typical  coagulum,  however,  may  be  produced,  if  either  a  washed  fibrin-clot,  a  small 
quantity  of  blood  serum,  or  a  solution  containing  thrombin  is  added  to  it. 

Fibrinogen  is  a  protein.  It  belongs  to  the  group  of  the  globulins.  From  para- 
globulin,  it  may  be  distinguished  in  several  ways;  viz. :  it  coagulates  at  a  lower  tem- 
perature (55°  to  00°),  is  completely  precipitated  by  saturation  with  sodium  chlorid 
or  magnesium  sulpliate,  and  may  be  converted  into  the  insoluble  protein,  fibrin. 
Its  percentage  composition  has  been  given  by  Hammarsten  as:  C  52.93,  H  6.90, 
N  16.66,  S  1.25,  O  22.26.  According  to  Schmiedeberg  its  molecular  composition 
is:  C108H162N30SO34. 

Fibrin. — In  accordance  with  the  analyses  of  Hammarsten,  fibrin  possesses  the 
same  composition  as  fibrinogen.  This  similarity,  however,  is  only  an  apparent 
one,  because  as  botl;  substances  are  extracted  with  alcohol  and  ether,  the  fat  and 
lipoid  are  not  included  inj  the  analysis,  and  hence,  the;  remaining  substance 
appears  as  a  protein  of  the  composition  just  given.  Wooldridge,' in  fact,  believes 
that  these  bodies  are  not  identical  at  all  but  show  certain  differences  in  the  lipin 
part  of  their  molecules.  Fibrinogen  as  it  exists  in  the  plasma  is  regarded  as  a 
lecithoprotein  or  as  a  substance  containing  much  phospholipin.  Fibrin  is  similarly 
constituted,  but  contains  less  phospholipin.  The  chemical  process  underlying  the 
formation  of  the  relatively  insoluble  fibrin  is  not  clearly  understood.  Fibrinogen 
is  said  to  change  first  into  soluble  fibrin,  and  later  on  into  fibrin  proper.  In  accord- 
ance with  Hammarsten,  ^a  hydrolysis  results  which  splits  the  molecule  of  the  fibrin- 
ogen into  fibrin  and  fibrinoglobulin.  Other  investigators,  however,  assume  that 
physicochemical  alterations  are  incited  which  lead  to  an  intramolecular  rearrange- 
ment of  the  fibrinogen.  Thus,  fibrinogen  is  regarded  as  the  hydrosol,  and  fibrin  as 
the  hydrogel  of  one  and  the  same  globulin.^  It  is  also  supposed  that  a  precipita- 
tion of  the  fibrinogen  by  electrolytes  takes  place  soon  after  the  thrombin  has  incited 
its  decomposition.'* 

If  the  blood  is  beaten  with  a  rough  piece  of  wood  while  it  is  being  withdrawn 
from  the  blood-vessel,  the  fibrin  accumulates  upon  the  stick  in  the  form  of  an 
elastic  fibrous  mass,  the  springiness  of  which  is  lessened  as  soon  as  the  shreds  are 
torn  or  are  separated  from  their  attachments.  This  deposit  is  always  contamin- 
ated with  red  corpuscles  and  lymphoid  cells.  If  it  is  essential  to  obtain  this  sub- 
stance in  a  pure  form,  it  should  be  prepared  from  filtered  plasma,  or  from  filtered 
transudates;  moreover,  it  should  be  noted  that  if  it  is  allowed  to  remain  in  contact 
with  the  blood  from  which  it  has  been  removed,  it  dissolves  in  part.  While  the 
factors  which  are  responsible  for  this  fibrinolysis  are  not  known,  it  is  believed  that 
they  are  of  enzymic  origin.  Fibrin  derived  from  the  blood  of  different  animals, 
exhibits  somewhat  different  properties.  It  is  insoluble  in  water,  alcohol  and  ether, 
but  may  be  dissolved  in  dilute  salt  solutions  at  a  temperature  of  40°  C. 

B.  INTRAVASCULAR  CLOTTING 

It  has  been  found  that  the  blood  retains  its  fluid  condition  only  as 
long  as  it  is  permitted  to  remain  in  contact  with  the  normal  intima  of 
the  blood-vessels.  This  statement  implies  that  coagulation  must  set 
in  as  soon  as  the  blood  is  brought  in  relation  with  a  foreign  body,- 
whether  this  be  outside  or  inside  the  vascular  channels.     Intravascular 

^Collected  papers,  Rep.  to  the  Scient.  Comm.  of  the  Grocer's  Assoc,  i,  201; 
ii,  266. 

*  This  view  is  also  held  by  Schmiedeberg  (Archiv  fiir  Exp.  Path,  und  Pharm., 
xxxix)  and  Heubner  (ibid.,  xhx,  1903,  229). 

^  Iscovesco,  Soc.  Biol.,  Ix  andlxi,  1906. 

*  Friedemann  and  Friedenthal,  Zeitschr.  fiir  exp.  Path.,  iii,  1906,  73. 


218  THE   BLOOD 

clotting  may  be  incited  by  introducing  a  solid  object  directly  into  the 
blood-stream,  or  by  causing  a  trauma  of  the  blood-vessel  and  surround- 
ing tissue  so  that  these  will  be  changed  into  destructive  agents.  A 
thin  layer  of  fibrin  is  then  deposited  upon  the  injured  area,  more  and 
more  material  being  gathered  in  gradually  until  a  clot  has  been  formed 
which  may  occlude  the  entire  lumen  of  the  blood-vessel.  When  fully 
formed,  a  clot  of  this  kind  is  known  as  a  thrombus.  After  the  blood 
current  has  played  against  this  intravascular  coagulum  for  some  time, 
pieces  of  it  may  be  broken  off  and  carried  to  distant  parts  of  the  cir- 
culatory system,  where  they  may  obstruct  the  blood  flow  and  give  rise 
to  an  anemia  and  functional  uselessness  of  the  tissues  situated  distally 
to  the  block.  A  floating  thrombus  is  known  as  an  embolus.*  The 
ultimate  outcome  of  a  condition  of  this  kind  depends  upon  the  freedom 
with  which  the  tissues  so  cut  off  may  be  supplied  with  blood  by  anas- 
tomosing vessels.  It  need  scarcely  be  mentioned  that  the  lining  of 
the  blood-vessels  may  also  be  changed  into  a  destructive  agent  by  the 
products  of  bacteria,  and  other  toxic  substances  circulating  through 
the  system. 

Intravascular  clotting  may  also  be  incited  experimentally  by  the 
injection  of  solutions  of  various  substances.  In  accordance  with  the 
statements  made  previously,  it  might  be  supposed  that  thrombin  or 
thromboplastic  substance  would  act  as  very  powerful  coagulating  agents 
when  introduced  into  the  circulation,  but,  curiously  enough,  the  system 
possesses  the  power  of  protecting  itself  against  them.  Howell  believes 
that  the  action  of  thrombin  is  neutralized  in  this  case  by  a  greater 
production  of  antithrombin. 

The  effects  obtained  with  tissue  extracts  and  solutions  of  thrombo- 
plastic substance  are  rather  perplexing.  Extensive  clotting  most 
frequently  results  in  consequence  of  the  injection  of  moderate  amounts 
of  thrombokinase  and  extracts  of  organs  rich  in  cellular  elements,  such 
8S  the  thymus  and  lymph  glands.  It  has  been  suggested  by  Wool- 
dridge  that  these  extracts  contain  thrombokinase.  Their  injection, 
therefore,  leads  to  the  same  results  as  the  liberation  of  this  body  in 
shed  blood.  It  is  to  be  noted,  however,  that  small  quantities  of  these 
extracts  diminish  the  coagulabHity  of  the  blood.  The  former  reaction 
is  usually  designated  as  the  positive  and  the  latter  as  the  negative 
phase  of  the  injection,  but  as  a  lessening  of  the  coagulabiUty  cannot  be 
obtained  in  this  manner  during  extravascular  clotting,  it  must  find  its 
origin  in  certain  functional  peculiarities  of  the  tissue  cells,  analogous 
to  their  behavior  toward  toxins.  It  is  a  well-known  fact  that  the 
injection  of  diphtheria  toxin  gives  rise  to  a  certain  amount  of  antitoxin 
in  the  course  of  two  or  three  days.  Additional  injections,  however, 
most  generall}'  produce  a  complete  disappearance  of  the  antitoxin 
until,  a  day  or  two  later,  it  again  makes  its  appearance  in  quantities 
much  larger  than  those  present  before  the  second  injection.     It  should 

^  The  circulation  may  also  be  obstructed  by  embolisms  of  different  origin,  for 
example,  by  droplets  of  fat  or  bubbles  of  air. 


THE  COAGULATION  OF  THE  BLOOD  219 

also  be  mentioned  that  the  effects  of  Witte's  peptone,  or  of  hirudin  are 
only  temporary.  It  seems,  therefore,  that  certain  tissue  cells  possess 
the  power  of  rendering  these  substances  inert,  the  probability  being 
that  this  neutrahzation  is  brought  about  by  the  discharge  of  an  anti- 
coagulating  agent. 

The  fact  that  the  blood  does  not  clot  while  traversing  the  normal 
circulatory  channels,  may  therefore  be  explained  in  two  ways,  namely: 
(a)  by  saying  that  thrombokinase  is  not  hberated  as  long  as  the  blood 
is  prevented  from  coming  in  contact  with  a  destructive  agent  and  (h), 
that  a  certain  amount  of  an  anticoagulating  substance  is  always  pres- 
ent in  the  blood  which  serves  the  purpose  of  retaining  the  thrombin 
in  its  inactive  condition. 

THE  TIME  OF  COAGULATION 

The  period  intervening  between  the  moment  of  the  withdrawal  of 
the  blood  and  the  moment  when  it  has  assumed  a  jelly-like  consistency, 
is  known  as  the  coagulation  time.  Various  methods  have  been  devised 
to  determine  its  length,  but  none  of  them  gives  absolutely  rehable 
results.  Vierordt^  employed  a  glass  tube  possessing  a  diameter  of  1 
mm.  and  a  length  of  5  cm.  A  white  horse  hair 
having  been  placed  lengthwise  in  this  tube,  the 
latter  was  then  filled  with  the  blood  to  be  tested. 
After  a  few  moments  the  hair  was  withdrawm 
at  intervals  and  a  short  distance  each  time,  until 
small  coagula  began  to  adhere  to  it.  Possibly 
the  simplest  procedure  is  to  collect  a  small  quan- 

J.-J.  ri-ij-  j.j.j.i_  r  1-  •  Fig.   117 — Coagl'latiox 

tity  or  blood  in  a  test  tube  oi   ordinary  size,         rj,^^^  ^^  Blood. 
noting  the  time  of  its  withdrawal,  and  to  deter-       ^_  chamber  in  which 
mine  again  the  moment  when  it  is  possible  to  drop  is  suspended  from 
invert  this  tube  without  causing  the  blood  to  ""'"^,^"^  ""/  "e'^^  ^^^  '^^'^^^ 

,     -^  ,,  ocular  of  microscope. 

flow  out.     Brodie    and    KusselP    advocate  the 

following  method:  A  drop  of  freshly  drawn  blood  is  placed  upon 
the  polished  tip  of  a  conical  piece  of  glass  (Fig.  117).  The  latter  is 
then  inverted  and  placed  in  a  small  compartment  underneath  a  lens 
magnifying  thirty  diameters.  Very  weak  currents  of  air  are  brought  to 
bear  upon  the  lateral  surface  of  this  suspended  drop  at  intervals  of 
thirty  seconds  until  the  corpuscles  cease  to  spin  around  and  the  ex- 
ternal layers  have  assumed  a  gelatinous  consistency.  Biirker^  employs 
a  glass  sHde  the  central  area  of  which  is  depressed  and  surrounded  by 
a  low  wall  of  glass.  A  drop  of  boiled  water  is  then  placed  in  this  com- 
partment, to  which  is  added  a  drop  of  fresh  blood.  The  time  of  mixing 
these  fluids  is  accurately  recorded  by  means  of  a  kymograph  and 

1  Archiv  fur  Heilkunde.  1878,  193. 

2  Jour,  of  Physiol.,  xxi,  1897,  403;  also  see:  Pratt,  Archiv  fiir  Exp.  Path, 
und  Pharm.,  .xlix,  1903,  299. 

'  Pfliiger's  Archiv,  cii,  1904,  57. 


A 


220  THE    BLOOD 

Jaquet  chronometer.  At  intervals  of  half  a  minute  the  hair-like  end 
of  a  glass  rod  is  drawn  through  this  mixture  from  side  to  side  until  it 
catches  the  first  shreds  of  fibrin.  This  moment  is  again  noted.  Can- 
non and  MendenhalP  have  devised  a  small  instrument,  known  as  a 
graphic  coagulometer,  consisting  of  a  horizontal  writing  lever  and  a 
vertical  glass  tube  containing  the  blood  to  be  tested  (Fig.  118).  A 
coil  of  very  thin  copper  wire  is  suspended  in  this  blood,  its  other  end 
being  attached  to  the  tip  of  the  lever.  The  latter  is  counterpoised 
in  such  a  manner  that  it  retains  its  horizontal  position  without  supports 
as  soon  as  the  blood  is  coagulated.  This  procedure,  therefore,  con- 
sists in  releasing  the  lever  at  intervals  of  30  seconds  until  its  pointer 
fails  to  rise. 

The  experiments  of  Vierordt  have  shown  at  an  early  date  that  the 
coagulation  time  of  human  blood  is  subject  to  considerable  daily  varia- 
tions.    During  the  morning  hours,  he  found  its  value  to  be  9.6  minutes, 


^ *    id 


s 


Fig.  118. — Graphic  Coagulometer. 
A,  writing  lever  counterpoised  by  weight  W  and  supported  at  S  and  R;  P,  rod  by- 
means  of  which  supports  may  be  removed;  C,  wire  which  rests  with  its  ring-like  end; 
D,  in  blood  drawn  into  cannula  C. 

after  the  noon-day  meal  10.1  minutes,  and  in  the  evening  8.1  minutes. 
This  investigator,  however,  did  not  protect  the  blood  against  changes 
in  the  temperature  of  the  air  and  also  failed  to  detect  the  first  indica- 
tions of  clotting  with  any  degree  of  accuracy.  For  this  reason,  his 
tests  have  led  to  values  which  are  somewhat  higher  than  those  sub- 
mitted by  other  investigators.  Biirker,  who  repeated  these  experi- 
ments under  more  favorable  circumstances,  obtained  values  ranging 
between  6  and  12  minutes.  The  latter  were  gotten  in  the  morning 
and  the  former  in  the  evening. 

The  coagulation  time  differs  considerably  in  different  individuals. 
Hewson  states  that  the  average  time  is  3  to  4  minutes,  while  Gendrin 
gives  it  as  10  hiinutes.  Biirker,  however,  found  a  rather  close  agree- 
ment, but  only  after  he  had  thoroughly  controlled  such  factors  as 
age,  sex,  temperature  and  the  time  of  day.  His  values  range  between 
6  and  7.5  minutes.  Those  of  Cannon  and  Mendenhall  average  4.9 
minutes.  The  first  signs  of  clotting  usually  appear  within  3  or  4 
minutes  after  the  withdrawal  of  the  blood.  The  average  time  in  the 
dog  and  cat  is  2.5  to  4  minutes. 

1  Am.  Jour,  of  Physiol.,  xxxiv,  1914,  225. 


THE    COAGULATION    OF   THE   BLOOD  221 

Somo  persons,  who  are  known  as  blcodors,  exhibit  a  decided  tend- 
ency toward  delayed  clotting  which  frequently  endangers  their  life 
(hemophilia).  Hemorrhages  from  the  mucous  surfaces  may  occur 
almost  at  any  time  and  without  apparent  cause.  Extravasations 
may  also  result  into  the  subcutaneous  tissue  and  the  joints,  as  well  as 
into  the  different  serous  cavities  of  the  body.  This  condition,  the  cause 
of  which  is  imknown,  is  inherited  and  usually  destroys  the  male  line, 
i.e.,  it  remains  dormant  in  the  females  but  may  be  transferred  by 
them  to  their  male  offsprings. 

CONDITIONS  INFLUENCING  THE  COAGULATION  TIME 

Temperature. — In  general  it  may  be  said  that  high  temperatures 
accelerate  and  low  temperatures  retard  the  clotting.  For  this  reason, 
hot  cloths  are  often  applied  to  bleeding  surfaces,  the  heat  acting  merely 
as  an  agent  to  intensify  the  chemical  changes  underlying  the  process 
of  coagulation.  Conversely,  a  sample  of  blood  may  be  retained  in  its 
fluid  condition  for  a  relatively  long  period  of  time  by  surrounding  the 
receptacle  in  which  it  is  kept  with  crushed  ice.  This  result  may  be 
made  the  more  striking  if  blood  is  used,  the  normal  clotting  time  of 
which  is  long;  for  example,  that  of  the  horse  or  that  of  invertebrates. 
If  blood  is  heated  to  60°  C,  it  loses  its  power  of  coagulation,  because 
the  fibrinogen  is  precipitated  at  this  temperature. 

The  effect  of  heat  and  cold  seems  to  be  directly  proportional  to  the 
destruction  of  the  thrombocytes,  but  while  these  elements  disintegrate 
more  readily  at  high  than  at  low  temperatures,  they  are  also  broken 
up  at  the  temperature  of  the  body.  The  fact  that  the  blood  of  cold- 
blooded animals  clots  very  slowly  is  frequently  cited  as  proving  that 
low  temperatures  tend  to  retard  the  coagulation,  but  it  is  more  than 
likely  that  this  is  merely  a  coincidence  and  that  the  correct  explanation 
is  to  be  sought  in  fundamental  differences  in  the  manner  of  clotting 
of  this  type  of  blood.  ^ 

Methods  of  Collecting  the  Blood. — If  the  blood  is  drawn  into  a 
receptacle  with  a  smooth  surface,  it  does  not  clot  so  readily  as  if  col- 
lected in  one  possessing  a  rough  surface.  It  is  also  true  that  the  coagu- 
lation sets  in  more  quickly  in  a  receptacle  which  presents  a  large  area 
to  the  blood.  For  this  reason,  the  clotting  may  be  greatly  retarded 
by  oiling  the  walls  of  the  vessel  or  by  coating  them  with  wax,  paraffin, 
or  agar.  In  explanation  of  these  differences  it  need  only  be  mentioned 
that  the  liberation  of  the  activating  agent  depends  primarily  upon  the 
destruction  of  the  thrombocytes.  Quite  naturally,  an  oiled  receptacle 
or  one  possessing  a  small  surface,  must  be  less  injurious  to  these  cells 
than  one  presenting  the  opposite  characteristics. 

The  same  explanation  holds  true  in  the  case  of  blood  which  is 
retained  in  its  fluid  state  by  surrounding  it  with  the  normal  lining  of 
the  blood-vessel.     Thus,  if  a   certain  segment  of  a  vein  is  filled  by 

^  L.  Loeb,  Archiv  path.  Anat.,  clxxxv,  1906,  160. 


222  THE   BLOOD 

placing  a  ligature  upon  its  central  end  and  is  then  excised  after  having 
previously  ligated  its  distal  end,  the  blood  so  entrapped  remains  fluid 
for  many  days.  This  preparation,  which  is  known  as  the  "living  test 
tube,"  must  be  kept  under  proper  conditions  of  moisture  and  tem- 
perature, because  if  its  walls  are  injured,  it  will  act  in  the  same  manner 
as  any  other  foreign  body  and  cause  intravascular  clotting.  If  this 
preparation  is  suspended  for  a  time,  the  red  corpuscles  finally  settle  by 
gravity,  so  that  it  is  possible  to  obtain  the  supernatant  liquid  sepa- 
rately and  to  subject  it  later  on  to  coagulating  agents. 

Air  was  formerly  regarded  as  a  necessary  factor  in  coagulation,  but 
as  this  process  also  takes  place  in  blood  which  has  been  collected  in  a 
tube  above  mercury,  this  view  can  no  longer  be  held.  Accumulations  of 
air  in  the  form  of  larger  or  smaller  bubbles  act  as  foreign  bodies  and 
hasten  the  destruction  of  the  thrombocytes  and  the  liberation  of 
thrombokinase. 

Substances  Derived  from  the  Tissues. — The  observation  has  been 
made  repeatedly  that  the  blood  of  certain  animals,  when  prevented 
from  coming  in  contact  with  the  neighboring  tissues,  clots  less  speedily 
or  remains  fluid  for  sometime  after  its  withdrawal.  This  is  true  espe- 
cially of  the  blood  of  birds,  reptiles  and  fishes,  which  clots  rather 
quickly  if  permitted  to  flow  across  the  incised  tissues,  but  fails  to 
coagulate  for  many  days  if  drawn  from  the  cannulized  blood-vessel 
directly  into  a  clean  and  dust-free  beaker.  This  result  indicates  that 
the  blood  of  these  animals  is  devoid  of  a  coagulating  agent,  although 
a  substance  of  this  character  is  contained  in  their  tissues.  The  plasma 
obtained  from  this  type  of  blood  also  remains  fluid  for  a  long  time,  but 
coagulates  within  a  few  minutes  if  an  extract  of  the  tissues  is  added  to 
it.  Under  ordinary  conditions,  however,  an  animal  of  this  kind  is 
fully  protected  against  serious  hemorrhage,  because  the  escaping 
blood  is  subjected  to  the  coagulating  agent  as  soon  as  it  leaves  the 
vascular  channel. 

Different  extracts  have  been  prepared  from  the  tissues  of  mammals 
which  markedly  accelerate  the  coagulation  of  the  blood.  The  active 
principle  contained  in  them  has  been  variously  designated  as  cell- 
globulin,  tissue-fibrinogen,  tissue  nucleoproteid,  coagulin,  and  zymo- 
plastic  substance.  HowelP  suggests  the  term  of  thromboplastic  sub- 
stance, because  it  permits  of  a  more  general  application,  and  refers 
merely  to  an  agent  which  accelerates  the  clotting  without  indicating 
the  manner  in  which  this  acceleration  is  brought  about.  A  substance 
of  this  character  has  been  obtained  by  Howell  from  certain  tissues  with 
the  help  of  ether  or  with  ether  and  alcohol.  It  is  known  as  kephalin, 
and  is  held  in  combination  with  a  protein  which  is  precipitated  at  a 
temperature  of  60°  C.  According  to  Howell,  this  body  possesses  the 
property  of  neutralizing  the  antithrombin,  while  others^  believe  that 
it  is  identical  with  fibrin  ferment  and  that  the  activation  of  the  pro- 

*  Am.  Jour,  of  Physiol.,  xxxi,  1912,  1. 

^  Moravitz,  Hofmeister's  Beitrage,  v,  1904.  133. 


THE  COAGULATION  OF  THE  BLOQD  223 

thrombin  to  thrombin  is  facihtatcd  by  it.  It  is  held,  however,  that 
fibrin  ferment  as  such  is  not  i)resent  in  the  tissues. 

Admixture  of  Neutral  Salts. — When  present  in  small  amounts,  the 
neutral  salts  act  ratlicr  favorably  upon  coagulation,  but  tend  to  retard 
this  process  as  soon  as  their  quantity  surpasses  a  certain  minimum. 
Thus,  a  27  per  cent,  solution  of  magnesium  sulphate  prevents  the  clot- 
ting for  a  long  time,  if  1  part  of  it  is  added  to  3  or  4  parts  of  blood. 
Sodium  sulphate  in  half-saturated  solution  manifests  a  similar  action, 
but  it  must  be  mixed  with  an  equal  quantity  of  blood.  In  all  these 
instances  the  corpuscles  settle  very  slowly,  but  their  deposition  may 
be  hastened  by  centrifugalization.  The  supernatant  plasma,  known 
as  "salted  plasma,"^  may  be  made  to  clot  later  on  by  diluting  it  suffi- 
ciently with  water  or  by  the  addition  of  a  few  drops  of  a  solution  of 
thrombin.  If  the  "salted"  blood  is  left  standing  for  a  day  before  it  is 
centrifugalized,  the  plasma  does  not  clot. 

Biirker  emphasizes  the  fact  that  weak  solutions  of  magnesium 
sulphate  tend  to  preserve  the  thrombocytes,  so  that  it  is  possible  to 
obtain  them  from  the  supernatant  plasma  long  after  the  red  cells 
have  separated  out.  The  deduction,  therefore,  seems  justified  that 
weak  solutions  of  the  neutral  salts  inhibit  the  formation  of  the  thrombin, 
while  strong  solutions  prevent  the  interaction  between  this  agent  and 
the  fibrinogen.^ 

Weak  solutions  of  sodium  chlorid  do  not  influence  the  coagulation, 
while  concentrated  solutions  of  this  salt  manifest  an  action  similar 
to  that  of  the  salts  mentioned  previously.  Thus,  it  is  possible  to 
prevent  the  clotting  by  drawing  the  blood  into  an  equal  volume  of 
a  10  per  cent,  solution  of  this  salt.  Sodium  carbonate  in  concentrated 
solution  and  bile  salts  also  retard  this  process. 

Decalcification  of  the  Blood. — Arthus  and  Pages^  have  shown  that 
the  blood  from  which  the  calcium  has  been  removed,  remains  fluid 
for  an  indefinite  period  of  time.  This  end  may  be  attained  by  col- 
lecting it  in  a  0.1  to  0.3  per  cent,  solution  of  sodium  or  ammonium 
oxalate.  It  should  be  remembered,  however,  that  it  may  be  made  to 
clot  at  any  time  subsequently  by  adding  a  proper  amount  of  a  calcium 
salt  to  it.  Furthermore,  it  has  been  shown  that  the  mere  presence  of 
dissolved  calcium  is  not  sufficient  to  incite  clotting,  but  that  it  must  be 
made  available  in  the  form  of  a  salt  held  in  an  ionized  state,  for  example, 
as  calcium  chlorid  or  sulphate.  The  oxalated  blood  may  be  subjected 
to  centrifugalization,  after  which  the  plasma  derived  from  it,  may  be 
treated  in  the  same  manner  as  other  non-coagulable  plasmas.  Thus, 
horse-blood  containing  0.1  per  cent,  sodium  oxalate,  will  yield  a 
perfectly  clear,  yellowish  plasma  which  displays  no  tendency  to  clot 
under  ordinary  conditions.  But  if  this  plasma  is  warmed  and  mixed 
with  a  solution  of  calcium  chlorid  drop  by  drop  in  excess,  it  will  give 

1  A.  Schmidt,  Zur  Blutlehre,  Leipzig,  1892. 

"^  Bordet  and  Gengou,  Ann.  Inst.  Past.,  xviii,  1904,  90. 

3  Jour.  Phys.,  xxii,  1890,  739. 


224  .  THE    BLOOD 

a  firm  coagulum,  from  which  a  perfectly  clear  serum  is  eventually 
separated. 

It  must  be  concluded,  therefore,  that  calcium  plays  an  important 
part  in  clotting.  The  controversy  regarding  the  precise  action  of  tiiis 
salt  initiated  by  Pekelharing,4ias  finally  beensettlcdby  Hammarsten,^ 
who  has  proved  that  it  plaj's  an  important  part  during  the  first  stage 
of  this  process.  This  deduction  is  based  upon  the  observation  that 
a  calcium-free  solution  of  fibrinogen  may  be  made  to  coagulate  by 
means  of  calcium-free  thrombin,  while  the  latter  cannot  be  formed  in 
the  absence  of  soluble  calcium  salts.  Again,  oxalate  plasma  contains 
no  fibrin  ferment,  but  gives  rise  on  cooKng  to  an  inactive  precipitate 
in  which  active  tkrombin  may  be  generated  at  anj^  time  by  the  addi- 
tion of  a  soluble  calcium  salt.  Obviously,  therefore,  the  calcium  serves 
the  purpose  of  activating  the  prothrombin  of  the  plasma,  but  when 
fully  formed,  the  action  of  the  thrombin  cannot  be  hindered  in  any 
way  by  the  precipitation  of  this  salt. 

Solutions  of  strontitun  citrate,  sodium  citrate  or  sodium  metaphos- 
phate  also  exert  a  retarding  influence  upon  coagulation.  Thus,  if 
sodium  citrate  is  added  to  blood  in  the  presence  of  a  calcium  salt,  a 
double  salt  of  sodium-calcium-citrate  is  formed,  and,  as  the  calcium 
is  retained  in  this  union  as  a  part  of  the  acid  radical,  it  cannot  partici- 
pate in  the  process  of  clotting.  A  similar  result  may  be  obtained  with 
sodium  fluorid  in  solutions  of  3  parts  of  this  salt  to  1000  parts  of  blood. 
If  thrombin  is  added  to  this  mixture,  coagtilation  sets  in  immediately. 
The  calcium  precipitates  a  portion  of  the  protein,  but  invariably 
incites  clotting  if  added  in  excess.  To  begin  with,  therefore,  the  cal- 
cium seems  to  be  held  as  a  fluorid  in  combination  with  a  part  of  the 
protein,  until  its  uncombined  portion  is  enabled  to  manifest  its  char- 
acteristic action.  Thus,  the  fluorid  binds  the  calcium  in  the  same 
manner  as  the  oxalates. 

Substances  of  Animal  Origin. — The  circulating  blood  of  the 
mammals,  and  especially  that  of  the  dog,  may  be  rendered  non-coagu- 
lable  by  the  procedure  of  peptonization  which  consists  in  injecting  a 
solution  of  commercial  peptone  ("\A'itte's)  intravenously.  To  attain 
the  aforesaid  restilt,  it  is  sufl&cient  as  a  rule  to  use  about  0.3  gram  of 
peptone  per  kilo  of  the  body  weight.  The  blood  of  a  peptonized 
animal  remains  fluid  for  hours  after  its  withdrawal,  and  non-coagulable 
plasma  may  be  obtained  from  it  by  the  use  of  the  centrifuge.  Pep- 
tone solutions,  however,  are  quite  miable  to  produce  this  effect  if  the 
animal  has  been  fed  shortlj^  before  the  injection  or  if  they  are  added 
to  fresh  normal  blood  after  it  has  been  withdrawn  from  the  body. 
It  has  also  been  noted  that  they  do  not  retard  the  clotting  very  ap- 
preciably when  introduced  into  the  peritoneal  ca^dty  instead  of  directly 
into  the  blood-stream.  This  method  of  rendering  the  blood  non- 
coagulable  cannot  be  recommended  for  experiments  upon  the  circula- 

^  Intern.  Beitriige  fiir  Virchow's  Festschrift,  i,  1891. 
*  Zeitschr.  fiir  phys.  Chemie,  xxii,  1896,  333. 


THE  COAGULATION  OF  THE  BLOOD  225 

tion,  because  the  peptone  tends  to  cause  a  certain  degree  of  vascular 
depression.  The  respiratory  movements  are  quickened  and  the  jjlood- 
pressurc^  frequently  drops  to  a  veiy  low  level. 

It  is  l)elieved  that  this  action  of  peptone  is  made  possible  by  the 
liberation  or  formation  of  a  substance  which  hinders  coagulation,  the 
so-called  antithrombin.^  As  the  latter  is  not  a  constituent  of  the 
peptone,  it  must  be  formed  subsequent  to  its  injection.  Nolf-  and 
others  believe  that  it  is  produced  in  the  liver,  because  the  exclusion 
of  this  organ  from  the  circulation  destroys  the  aforesaid  action  of  the 
peptone.  Moreover,  Delezenne^  has  succeeded  in  producing  an  anti- 
coagulating  agent  by  perfusing  the  excised  liver  with  a  peptone  solu- 
tion. It  seems  that  this  antibody  is  enabled  to  unfold  its  character- 
istic action  by  neutralizing  a  certain  quantity  of  the  fibrin  ferment. 
It  is  also  of  interest  to  note  that  the  peptone  gives  rise  to  a  certain 
degree  of  resistance  or  immunity,  because  if  a  second  injection  is  made 
a  day  later,  it  fails  as  a  rule  to  render  the  blood  non-coagulable.  Ex- 
tracts of  crayfish  or  of  mussels  act  in  a  somewhat  similar  manner. 

Leech  Extract  and  Snake  Poisons. — A  substance  possessing  a 
marked  inhibitor  power  upon  coagulation  has  been  obtained  by  Hay- 
craft''  from  leeches.  In  its  pure  crystalline  form  it  is  known  as  hirudin. 
Although  relatively  resistant  to  high  temperatures,  its  effectiveness 
may  be  materially  lessened  by  heating  it  to  100°  C.  It  behaves  in 
general  like  a  secondary  albumose.  When  injected  intravenously* 
or  when  mixed  with  fresh  blood  after  its  removal  from  the  body, 
it  produces  a  rather  lasting  non-coagulability.  Its  action  is  said  to 
depend  upon  the  production  of  an  antibody  which,  in  accordance  with 
the  statements  of  jMoravitz,  regulates  the  formation  of  thrombin  with 
quantitative  precision,  Pekelharing,  on  the  other  hand,  has  expressed 
the  opinion  that  it  prevents  the  liberation  of  those  bodies  upon  which 
the  production  of  the  fibrin  ferment  depends.  The  latter  view  has 
recently  been  advocated  by  Biirker  who  emphasizes  the  fact  that 
solutions   of   hirudin   act   preservatively   upon   the   blood   platelets. 

Substances  possessing  a  similar  action  have  been  found  in  Ixodes 
ricinus*'  and  in  ankhylostomum  caninum.''  In  this  connection  atten- 
tion should  also  be  called  to  the  biological  peculiarity  that  the  venoms 
of  snakes  may  act  either  acceleratory  or  inhibitory.     The  poison  of 

1  Fuld  and  Spiro,  Hofmeister's  Beitrage,  v,  1904,  or  Moravitz,  Archiv  fiir 
klin.  Med.,  Ixxix,  1903-4. 

2  Arch,  intern,  de  phys.,  ii,  1904-5. 
2  Arch,  de  phys.,  viii,  1896,  655. 

*  Arch.  f.  Exp.  Path.  u.  Pharm.,  xviii,  1884,  209.  It  has  been  isolated  by 
Franz  (Archiv  f.  Exp.  Path.  u.  Pharm.,  xlix).  The  leeches  are  dried,  pulverized 
and  extracted  with  normal  saline  solution.  It  suffices,  however,  to  use  only  the 
head  portions  of  these  animals,  because  the  active  substance  is  contained  in  the 
buccal  glands. 

*  Use  10  to  20  eg.  for  10  kg.  of  body  weight  in  10  to  20  c.c.  of  saline  solution,  and 
1  eg.  for  each  additional  kilo  of  weight. 

^  Sebatani,  Arch,  ital   de  bioL,  xxxi,  1899,  375. 
^  Loeb  and  Smith,  C.  Bact.,  x.xxvii,  1904,  37. 

15 


226  THE    BLOOD 

the  cobra,  for  example,  inhibits  the  coagulation  even  in  very  minute 
doses  in  vivo  as  well  as  in  vitro,  because  it  prevents  the  conversion 
of  the  prothrombin  into  thrombin.  The  venoms  of  other  snakes, 
for  example,  that  of  pseudechis  porphytaceus,^  behave  in  the  same 
manner  as  tissue-extracts,  but  the  question  whether  their  action  is 
identical  with  that  of  thrombin  or  of  thrombokinase,  has  not  been 
definitely  decided. 

Defibrination. — It  is  possible  to  hasten  the  formation  of  the  fibrin 
by  vigorously  whipping  the  blood  during  its  withdrawal  with  a  rough 
stick  of  wood  or  with  a  bundle  of  fine  wires.  The  shreds  of  fibrin 
then  adhere  to  the  wood,  while  the  blood  from  which  they  have  been 
removed  remains  fluid  for  an  indefinite  period  of  time.  Obviously, 
this  procedure  causes  a  rapid  destruction  of  those  cellular  elements 
from  which  the  thrombokinase  is  derived.  The  fact  that  the  fibrin 
may  be  separated  in  this  way,  is  made  use  of  at  times  in  rendering  cer- 
tain inoperative  aneurysms  less  dangerous  to  life.  The  blood  con- 
tained in  these  saccular  enlargements  of  the  blood-vessels,  is  coagulated 
by  the  insertion  of  several  long  needles  of  steel.  Acting  as  foreign 
bodies,  these  needles  incite  a  deposition  of  fibrin  in  constantly  in- 
creasing mass  until  the  entire  lumen  of  the  tumor  has  been  occluded. 

Menstrual  blood  is  commonly  regarded  as  being  non-coagulable. 
This  belief  is  erroneous,  because  coagula  are  always  present  in  the 
upper  portion  of  the  vagina.  Only  the  fluid  cruor  mixed  with  mucus 
escapes.  It  is  true,  however,  that  the  mucus  retards  the  clotting, 
because  it  tends  to  smoothen  the  surface  of  this  passage  and  to  separate 
the  individual  masses  of  fibrin  more  widely  from  one  another. 


CHAPTER  XX 


THE  TOTAL  QUANTITY  AND  DISTRIBUTION  OF  THE  BLOOD. 

LOSS  OF  BLOOD 

Quantity  of  Blood. — It  was  formerly  thought  possible  to  determine 
the  total  amount  of  blood  present  in  an  animal  by  simply  opening  an 
artery  and  permitting  the  blood  to  escape  until  it  ceased  flowing. 
It  must  be  evident,  however,  that  this  procedure  is  open  to  certain 
objections,  because  a  considerable  portion  of  the  blood  is  always 
entrapped  in  the  finer  ramifications  of  the  vascular  system  as  well  as  in 
the  central  veins.  Welker-  has  advocated  the  following  method. 
A  small  amount  of  blood  is  withdrawn  and  diluted  with  saline  solu- 
tion in  the  proportion  of  1 :  500.     This  mixture,  designated  as  solution 

1  Martin,  Jour,  of  Physiol.,  xxxii,  1905,  207. 

"^  Zeitschr.  fiir  rat.  Med.,  iv,  1858  (modified  by  Heidenhain). 


THE   TOTAL  QUANTITY    AND    DISTRIBUTION    OF   THE   BLOOD  227 

a,  is  set  aside  in  a  receptacle  of  known  capacity.  The  animal  is  then 
thoroughly  bled,  and  its  vascular  channels  washed  out  with  normal 
saline.  To  avoid  errors,  the  urinary  and  biliary  bladders  are  removed. 
The  different  organs  and  tissues  are  then  finely  divided  and  thoi-oughly 
extracted  with  saline.  This  mixture  (6)  is  subsequently  diluted,  until 
its  color  corresponds  precisely  to  that  of  solution  a  when  placed  in 
the  same  kind  of  receptacle.  If  the  volume  of  solution  h  is  now  divided 
by  500,  the  quotient  indicates  how  many  times  the  quantity  of  blood 
contained  in  solution  a  is  contained  in  solution  h. 

The  first  attempt  to  determine  the  quantity  of  blood  in  a  chemical  manner 
has  been  made  by  Grehant  and  (Juinquaud.^  Having  ascertained  the  volume  per 
cent,  of  oxygen  in  a  given  sample  of  blood,  the  animal  was  permitted  to  breathe  a 
known  volume  of  carbon  monoxid.  The  total  amount  of  CO  was  then  deter- 
mined and  also  the  volume  per  cent,  of  O  in  a  second  sample  of  blood.  The 
difference  in  the  volume  per  cent,  of  O  in  the  two  samples  corresponds  to  the  volume 
per  cent,  of  CO  in  the  blood,  because  CO  displaces  an  equal  volume  of  O.     The  total 

V 
quantity  of  blood  is  calculated  according  to  the  formula  -     X  100;      V    stands 

for  the  total  amount  of  CO  absorbed  by  the  blood,  and  v  for  the  volume  per  cent, 
of  CO,  i.e.,  for  the  number  of  cubic  centimeters  of  this  gas  for  each  cubic  centi- 
meter of  blood. 

The  method  of  Haldane  and  Smith^  is  based  upon  a  similar  principle.  It 
depends  upon  the  displacement  of  the  oxygen  from  oxyhemoglobin  by  carbon  mon- 
oxid. If  a  person  is  permitted  to  inhale  a  definite  volume  of  CO,  and  if  it  is  then 
found  by  means  of  a  hemoglobinometer  that  )^  of  the  hemoglobin  of  his  blood 
has  been  saturated  with  this  gas,  it  may  be  concluded  that  five  times  this  amount 
is  needed  to  charge  all  of  his  blood.  In  this  way  we  ascertain  what  might  be  called 
the  carbon  monoxid  capacity  of  the  blood.  We  know  that  the  amount  of  CO 
in  CO-hemoglobin  is  identical  with  the  amount  of  O  contained  in  0-hemoglobin, 
and  hence,  the  above  value  also  indicates  the  oxygen  capacity  of  the  blood.  Know- 
ing the  latter,  the  amount  of  hemoglobin  present  in  the  body  can  easily  be  as- 
certained, and  knowing  the  percentage  amount  of  the  latter,  the  total  volume 
of  the  circulating  blood  can  thereupon  be  calculated. 

To  illustrate:  A  certain  person  exhibits  the  color  of  the  100  percent,  stand- 
ard and  possesses  therefore  a  capacity  of  18.5  c.c.  of  oxygen  per  100  c.c.  of  blood. 
If,  after  the  inhalation  of  75  c.c.  of  carbonic  oxid  gas,  his  blood  is  found  to  be 
saturated  with  this  gas  to  the  extent  of  15  per  cent.,  an  equal  per  cent,  of  the 
18.5  c.c.  must  be  present  as  carbon  monoxid,  namely,  2.7  c.c.  Consequently, 
if  2.7  c.c.  of  carbon  monoxid  are  present  in  100  c.c.  of  blood  after  breathing  75  c.c. 
of  this  gas,  it  only  remains  to  be  determined  how  much  additional  gas  must  be 
inhaled  in  order  to  give  the  value  of  18.5. 

Thus,    2.7  c.c.  per  100  c.c.  of  blood  on  inhalation  of  75  c.c.  of  CO 

75 
1.0  c.c.  per  100  c.c.  of  blood  on  inhalation  of  ^-^  c.c.  of  CO 

7  5  X  18  5 
and  18.5  c.c.  per  100  c.c.  of  blood  on  inhalation  of  — — ,  _    -^  c.c.  of  CO 

This  implies  that  the  total  oxygen  capacity  is  500  c.c.  As  18.5  c.c.  of  this  amount 
are  contained  in  100  c.c.  of  blood,  the  total  volume  of  blood  which  will  carry  500 

c.c.  of  the  gas  is: r-^-z —  =  2727  c.c.     The  total  weight  of  this  mass  of  blood 

is  ascertained  by  multiplying  the  volume  with  the  specific  gravity. 

1  Compt.  rend.,  vii,  1883. 

2  Jour,  of  Physiol.,  xx,  1836,  295,  and  xxv,  1900,  497. 


228  THE    BLOOD 

Quincke^  attempted  to  estimate  the  blood  volume  from  the  change  in  the  blood 
counts  before  and  after  transfusion.  Lindemann-  calculates  the  volume  of  the 
blood  during  transfusion  with  the  help  of  the  following  factors:  c,  the  cell  per- 
centage by  volume  of  the  blood  introduced;  b,  the  quantity  of  blood  introduced, 
both  being  open  to  direct  measurement;  I,  the  cell  percentage  by  volume  of  the 
patient's  blood  after  the  transfusion ;  x,  the  initial  volume  and  a,  the  cell  content 
of  the  initial  volume.     Then: 

xa  +  be  =  l{x  +  b) 

xa  -]-  be  =  Ix  +  lb 

xa  —  Ix  =  lb  —  be 

x{a  —  I)  =  lb  —  be 
lb  -be 

X   =  r 

a  —  I 

Thus:  If  the  amount  of  blood  transfused  is  1500  c.c,  the  amount  of  blood  previously 
withdrawn  for  tests  70  c.c,  the  cell  volume  before  transfusion  13.7  per  cent.,  the 
cell  volume  after  transfusion  25.5  per  cent,  and  the  cell  volume  of  the  donor  40 
per  cent.,  then  the  blood  volume  of  the  patient  amounts  to : 

40X1500-25.5X1500       ,^.„  ,    „„  ,„,„     „ 

pr^r-;; z^rii =  1843  C.C.  +  70  C.C.  =1913  c.c. 

26. o  —  13.7 

The  circulating  blood  of  the  dog  is  estimated  at  about  7.7  per  cent, 
of  the  body  weight,  in  the  cat  and  rabbit  at  5  per  cent,  and  in  birds  at 
10  per  cent.  Similar  values  have  been  found  by  Bischoff^  and  Weber 
and  Lehmann^  in  guillotined  criminals.  Based  upon  these  early  figures, 
the  amount  of  blood  present  in  an  animal  has  always  been  calculated  at 
one-thirteenth  of  the  body  weight.  The  experiments  of  Haldane  and 
Smith,  however,  seem  to  prove  that  this  figure  is  too  high.  Having 
obtained  an  average  value  of  0.49  per  cent.,  these  authors  believe  that 
the  total  quantity  of  blood  in  man  equals  only  one-twentieth  of  the 
body  weight.  Thus,  a  man  weighing  70  kg.  possesses  about  3684 
grams  of  blood. 

While  the  assumption  that  the  quantity  of  blood  preserves  a  direct 
relationship  to  the  weight  of  the  body,  is  a  natural  one  to  make,  it 
should  be  remembered  that  we  are  not  dealing  with  perfectly  constant 
conditions,  because  the  weight  is  subject  to  frequent  changes.  A  de- 
position of  fat,  a  greater  development  of  the  musculature,  a  transfer  of 
lymph  and  other  temporary  and  permanent  alterations  are  prone  to 
interfere  with  the  establishment  of  such  a  relationship. 

The  Distribution  of  the  Blood. — The  blood  having  been  ejected 
from  the  heart,  is  distributed  to  the  different  tissues  and  organs  of  the 
body  in  amounts  commensurate  with  their  activities.  In  general,  it 
may  be  said  that  the  tissues  which  form  the  framework  of  the  body 
need  a  relatively  small  quantity,  because,  when  fully  grown,  their 
upkeep  and  additional  slight  growth  do  not  necessitate  intense 
metabolic  changes.     Glandular  tissues,  on  the  other  hand,  need  a 

1  Deutsch.  Archiv  fur  klin.  Med.,  xx,  1877,  27. 

2  Jour.  Am.  Med.  Assoc,  Ixx,  1918,  1210.  Mention  should  also  be  made  of 
the  antitoxin  method  of  von  Behring  (Munchener  med.  Wochenschr.,  Iviii,  1911. 
655). 

3  Zeitschr.  fiir  Zoologie,  vii,  1855  and  ix,  1857. 

*  Zeitschr.  fiir  physiolog.  Chemie.,  Leipzig,  1853. 


THE    TOTAL   QUANTITY    AND    DISTRIBUTION    OF    THE    BLOOD  229 

much  larger  quantity,  because  the  production  of  a  secretion  or  excre- 
tion always  presupposes  an  abundant  supply  of  fresh  material.  It 
should  also  b(^  noted  that  an  organ  may  receive  a  large  amount  of 
blood  at  any  given  time  but  may  not  retain  much  of  it.  Again,  it 
may  receive  only  a  small  quantity  of  blood,  but  hold  a  considerable 
portion  of  it  in  reserve  as  "residual  blood."  To  illustrate:  The  in- 
testine of  a  dog  of  medium  weight  is  supplied  with  about  2.5  c.c.  of 
blood  in  a  second,  or  150  c.c.  in  a  minute.  While  this  amount  may 
seem  to  be  unusually  large,  it  should  ho  remembered  that  the  intestine 
of  an  animal  of  this  kind  weighs  about  500  grams,  so  that  the  150  c.c. 
of  blood  must  actually  be  distributed  to  500  grams  of  tissue  substance. 
Hence,  as  only  about  30  c.c.  of  blood  are  allotted  to  each  100  grams  of 
intestine  in  a  minute,  this  organ  cannot  be  said  to  be  very  vascular. 
The  reverse  relationship  exists  in  the  case  of  the  kidney.  While  the 
blood-supply  of  this  organ  is  as  copious  as  that  of  the  intestine,  its 
vascularity  must  be  much  greater,  because  its  average  weight  is  only 
40  to  50  grams.  In  the  succeeding  table^  the  different  organs  of  the 
dog  have  been  arranged  in  accordance  with  the  amounts  of  blood  re- 
ceived by  them  per  100  grams  of  substance  and  per  minute. 

5  c.c.  for  the  post,  extremity  58  c.c.  for  the  spleen 

12  c.c.  for  the  skeletal  muscle  59  c.c.  for  the  liver  (venous) 

20  c.c.  for  the  head  84  c.c.  for  the  liver  (total  supply) 

21  c.c.  for  the  stomach  136  c.c.  for  the  brain 
25  c.c.  for  the  liver  (arterial)  150  c.c.  for  the  kidney 

30  c.c.  for  the  portal  organs,  com-       480  c.c.  for  the  suprarenal  body 

bined  560  c.c.  for  the  thyroid  gland 

31  c.c.  for  the  intestine 

According  to  these  results,  the  vascularity  of  the  liver  is  surpassed 
by  that  of  the  brain,  kidney,  adrenal  body  and  thyroid  gland.  But  if 
considered  solely  from  the  standpoint  of  the  blood-supply,  the  quantity 
allotted  to  this  organ  must  be  larger  than  that  of  any  other,  because 
as  it  receives  about  7.0  c.c.  in  a  second,  its  supply  per  minute  amounts 
to  more  than  400  c.c.  It  will  be  seen,  therefore,  that  the  blood  must 
complete  the  circuit  through  its  channels  once  in  about  every  three 
minutes.  In  accordance  with  the  analyses  of  the  respiratory  air  by 
Zuntz,^  Krogh'^  and  Boothby,"*  the  lungs  of  man  receive  more  than  3 
liters  of  blood  in  a  minute. 

The  data  presented  by  Ranke'^  tend  to  show  that  the  blood  is  distri- 
buted at  any  one  time  as  follows:  one-fourth  to  the  heart,  lungs  and 
central  blood-vessels,  one-fourth  to  the  liver,  one-fourth  to  the  mus- 
cles and  one-fourth  to  the  remaining  organs.  These  values  have  been 
obtained  by  measuring  the  amount  of  blood  contained  in  the  b  ood- 

1  Compiled  in  accordance  with  data  presented  by  Burton-Opitz  in  Pfliigei's 
Archiv,  cxxix,  1908,  and  Quarterly  Jour,  of  Physiol.,  iv,  1911. 
^  Zeitschr.  fur  Balneologie,  iv,  1912. 
^  Skand.  Archiv  fiir  Physiol.,  xxvii,  1912. 

*  Am.  Jour,  of  Physiol.,  xxxvii,  1915. 

*  Die  Blutverteilung  und  Thatigk.  der  Organe,  Leipzig,  1871. 


230  THE    BLOOD 

vessels  supplying  the  aforesaid  organs  after  having  previously  ligated 
them  at  the  same  time.  The  tissues  were  then  subjected  to  the  chromo- 
metric  test  described  previously. 

Loss  of  Blood. — The  blood  escaping  from  a  wound  exhibits  certain 
differences  in  color  which  are  dependent  upon  differences  in  the  loca- 
tion and  extent  or  depth  of  the  lesion.  A  bright  red  color  signifies 
arterial  bleeding  and  a  dark  red  color  a  venous  extravasation.  In 
either  case,  the  blood  escapes  in  large  volume,  and,  in  arterial  hemor- 
rhage, under  a  considerable  pressure.  In  capillary  bleeding,  on  the 
other  hand,  the  blood  oozes  out  slowly  as  fine  droplets  which  finally 
coalesce  to  form  a  flat  coagulum.  Its  color  is  intermediate,  provided, 
of  course,  that  its  oxygenation  has  not  been  interfered  with  by  such 
conditions  as  venous  stasis  or  arterial  hyperemia.  Hemorrhages  are 
described  as  primaiy  and  secondary,  the  latter  term  being  apphed 
to  those  losses  of  blood  which  may  occur  after  operations,  in  conse- 
quence of  a  belated  or  improper  union  of  the  parts.  They  are  also 
classified  as  internal  and  external,  according  as  to  whether  the  blood 
escapes  into  a  tissue  or  serous  cavity,  or  actually  reaches  the  surface  of 
the  bod}'. 

Repeated  small  hemorrhagic  extravasations,  or  a  single  large  hemor- 
rhage, frequentl}'  result  in  a  diminution  in  the  volume  of  the  circulat- 
ing blood  which  must  necessarily  endanger  the  maintenance  of 
proper  djmamical  conditions.  This  vascular  depression  may  finally 
become  so  acute  that  the  function  of  the  different  cells  of  the  body  is 
lost  completely,  that  of  the  nervous  centers  being  affected  first. 
Hemorrhages  may  also  prove  fatal  in  a  more  direct  way,  in  that  the 
blood  may  find  its  way  into  a  vital  structure,  and  render  it  functionally 
useless.  This  is  especially  true  of  hemorrhages  from  the  cerebral  ar- 
teries into  the  adjoining  nervous  tissue.  The  complex  of  symptoms 
resulting  therefrom,  is  known  as  apoplexy. 

Small  losses  of  blood  are  readily  compensated  for  b}'  a  temporary 
diminution  in  the  size  of  the  blood-bed  and  a  regeneration  of  the  fluid 
and  corpuscular  elements  lost.  The  fluid  portion  of  the  blood  is 
quickly  replaced  by  a  transfer  of  Ijinph  from  the  tissue  spaces  and 
IjTnphatic  channels.  The  regeneration  of  its  corpuscular  constituents, 
however,  requires  a  much  longer  time,  because  their  formation  depends 
upon  the  activity  of  the  hematopoietic  tissues  which  is  gradual  and 
cannot  be  made  to  surpass  a  certain  maximal  value.  In  case  the 
loss  of  blood  has  been  severe,  it  may  not  be  possible  to  effect  a  compen- 
sation by  ordinary  physiological  means,  and  an  artificial  restitution 
of  the  blood  lost  must  be  resorted  to.  This  end  is  accomplished  by 
the  processes  of  infusion  and  transfusion. 

The  former  procedure  purposes  to  replace  the  fluid  part  of  the  blood  directly 
by  an  artificial  medium.  A  sterile  0.6  per  cent,  solution  of  sodium  chlorid,  heated 
to  the  temperature  of  the  body,  is  usually  employed.  If  the  hemorrhage  has  been 
very  severe  and  if  the  relaxation  of  the  vascular  system  is  extreme,  a  small  amount 
of  adrenalin  should  be  added  to  the  infusion  liquid.  As  this  agent  constricts  the 
blood-vessels,  thereby  lessening  the  size  of  the  blood-bed,  the  blood  pressure  will 


THE   TOTAL  QUANTITY   AND    DISTRIBUTION    OF   THE   BLOOD  231 

be  more  quickly  restored  than  if  the  saline  alone  is  used.  For  the  same  reason  it 
has  recentlj"  been  advocated  to  raise  the  viscosity  of  this  medium  by  the  addition 
of  gelatin.^  The  heart  reacts  much  sooner  if  it  is  made  to  contract  against  a 
moderate  peripheral  resistance.  Attention  should  also  be  called  to  the  fact  that 
the  loss  ot  pressure  during  the  hemorrhage  permits  of  the  occurrence  of  certain 
reflexes  which  tend  to  prevent  a  fatal  loss  of  blood  by  diminishing  the  force  and 
frequency  of  the  heart  beat  and  by  constricting  the  bleeding  vessels  at  the  seat  of 
the  injury. 

The  term  transfusion  is  applied  to  the  procedure  purposing  to  displace  or  to 
replace  a  portion  of  the  blood  of  an  animal  by  the  blood  of  another  animal.*  If  ac- 
complished by  the  direct  method,  an  intimate  connection  is  made  between  a  blood- 
vessel of  the  donor  and  a  vein  of  the  recipient  by  means  of  a  special  cannula.' 
The  blood-vessels  of  the  forearm  are  generally  selected  if  the  transfusion  is  to  be 
performed  upon  man.  Defibrinated  blood  has  also  been  made  use  of,  but  this 
procedure  is  only  permissible  in  animal  experimentation,  because  the  defibrination 
requires  time  and  as  the  blood  is  subjected  during  this  process  to  the  influence  of 
foreign  bodies,  it  is  difficult  to  retain  it  in  an  aseptic  condition.  Moreover,  as 
the  formation  of  fibrin  is  preceded  by  the  production  of  certain  agents  which  may 
in  part  remain  uncombined,  the  danger  of  intravascular  clotting  of  the  blood  of  the 
recipient  is  not  at  all  remote  The  indirect  method  of  transfusion  necessitates 
the  use  of  a  receptacle  in  which  the  blood  of  the  donor  is  retained  for  a  brief  period 
of  time  until  permitted  to  flow  into  the  veins  of  the  recipient.  This  procedure  is 
also  open  to  serious  objections,  because,  whatever  precautions  are  taken,  the  danger 
of  coagulation  cannot  be  excluded  with  absolute  certainty  by  the  addition  of  an 
anticoagulating  agent  nor  by  the  use  of  oiled  and  paraffined  receptacles. 

A  method  which  is  regarded  with  much  favor  at  the  present  time  is  the  so-called 
citrate  method.*  Having  applied  a  tourniquet  to  the  arm  of  the  donor,  a  cannula 
is  inserted  in  one  of  the  larger  veins  at  the  elbow  (median  cephalic).  The  blood  is 
collected  in  a  graduated  cjdinder  containing  a  2  per  cent,  solution  of  sodium  citrate. 
If  50  c.c.  of  blood  are  to  be  obtained,  50  c.c.  of  the  solution  are  taken  so  that  a  two 
per  thousand  mixture  is  effected.  The  blood  is  then  rapidly  transferred  to  a 
salvarsan  apparatus  containing  20  to  30  c.c.  of  a  physiological  solution  of 
sodium  chlorid,  and  is  permitted  to  run  into  the  punctured  vein  of  the  recipient  by 
gravitation. 

The  direct  transfer  of  blood  from  the  donor  to  the  patient  was  conceived  at  an 
earh^  date,^  and  has  been  practised  repeatedly  since  the  middle  ages,  either  to 
replace  blood  lost  by  hemorrhage  or  to  displace  blood  rendered  useless  bj'  disease. 
It  must  be  conceded,  however,  that  the  high  hopes  entertained  for  this  procedure 
as  a  curative  means  have  not  been  realized.  In  the  first  place,  it  is  conceivable 
that  the  transfer  of  blood  from  the  donor  through  an  ordinary  connecting  cannula 
is  Uable  to  hberate  the  agents  which  subsequently  cause  intravascular  clotting  in 
the  recipient.  An  unprotected  cannula  acts  as  a  foreign  body,  and  hence,  great 
care  must  always  be  taken  to  keep  the  blood  in  relation  with  the  normal  lining  of 

^  Bayliss,  Proc.  Royal  Soc,  London,  1917. 

2  Vogel  and  McCurdv,  Arch.  Int.  Med.,  Dec,  1913;  also  see:  Robertson,  Jour. 
Exp.  Med.,  xxvi,  1917,  221. 

3  Esmarch  (1877)  used  hydrostatic  pressure  to  force  defibrinated  blood  into 
the  vein.  In  1900  he  advocated  the  use  of  normal  saline  solutions.  The  transfer 
of  blood  from  one  human  being  into  another  through  the  agency  of  a  receptacle 
was  first  practised  by  Ziemssen  (1892). 

*  Carbat,  Jour.  Am.  Med.  Assoc,  Ixvi,  1915;  Lewisohn,  ibid.,  Ixviii,  1917,  826, 
and  Pemberton,  Surg.,  Gynec.  and  Obst.,  xxviii,  1919,  262. 

*  Savonarola  mentions  the  case  of  Pope  Innocent  VII  who  was  bled  and  whose 
blood  was  injected  into  two  young  men.  These  men  were  bled  later  on  and  their 
blood  passed  into  the  veins  of  the  Pope.  The  result,  however,  did  not  warrant 
a  repetition  of  this  procedure,  because  all  three  men  died. 


232  THE   BLOOD 

the  blood-vessels.  In  recent  years  a  number  of  cannulas^  have  been  devised  which 
make  a  direct  anastomosis  possible  and  obviate  the  danger  of  clotting.  The  second 
reason  is  intimately  associated  with  the  hemolytic  property  of  the  blood.  As  will 
be  shown  later,  the  body  fluids  of  different  animals  contain  certain  agents  which 
are  prone  to  cause  serious  injury  to  the  blood  of  the  recipient.  The  constituents 
primarily  involved  are  the  red  cells  which  are  destroyed  in  varying  numbers  until 
a  proper  aeration  of  the  tissues  can  no  longer  be  effected. 

Clearly,  therefore,  the  blood  of  the  donor  should  first  be  tested  as  to  its  hemo- 
l.vtic  power  before  it  can  safely  be  introduced  into  the  recipient.  It  may  rightly  be 
assumed  that  the  blood  of  a  widely  divergent  species  is  not  at  all  suitable  for  trans- 
fusion, because  its  properties  would  most  likely  be  very  imlike  those  of  the  blood 
of  the  recipient.  For  similar  reasons  it  may  be  concluded  that  the  blood  of  an 
animal  that  is  closely  related  to  the  recipient,  is  least  prone  to  incite  hemolysis. 
Thus,  transfusions  upon  human  beings  will  prove  less  dangerous  and  promise  better 
results  if  a  near  relative  is  selected  as  the  donor. 

1  Carrel,  Med.  Record,  Ixxxii,  1912,  1013. 


SECTION  V 
THE  LYMPH 


CHAPTER  XXI 
PROPERTIES  AND  FORMATION  OF  LYMPH 

General  Consideration. — The  lymph  forms  a  medium  of  inter- 
change between  the  blood  and  the  tissues.  This  is  made  necessary  by 
the  fact  that  the  blood  does  not  come  in  actual  contact  with  the  cells, 
but  remains  separated  from  them  by  the  Hning  of  the  capillaries.  It 
thus  plays  the  part  of  a  middleman,  and  carries  nutritive  material 
to  the  cells  in  exchange  for  the  products  of  their  metabolism.  It  is 
true,  however,  that  the  importance  of  the  lymph  as  a  distributing 
agent  varies  in  different  tissues,  because  some  of  them  are  more  vascular 
than  others,  and  are  equipped  for  this  reason  with  a  more  intricate  net- 
work of  blood-capillaries.  The  individual  cells  are  thus  brought  into 
closer  relation  with  the  blood-stream.  Under  less  favorable  conditions 
relatively  large  numbers  of  cells  are  grouped  around  a  single  blood 
channel,  so  that  the  nutrition  of  the  outlying  elements  can  only  be 
effected  by  a  correspondingly  greater  development  of  the  lymphatic 
vessels  and  spaces.  In  fact,  some  tissues  are  free  from  blood-vessels, 
their  nutrition  being  carried  on  by  the  lymph  filling  the  delicate  i  ter- 
cellular  spaces  permeating  them.  An  arrangement  of  this  kind  is 
present  in  the  central  zone  of  the  cornea  through  which  the  rays  of 
light  enter  the  eye.  It  need  scarcely  be  mentioned  that  the  presence 
of  blood-capillaries  in  this  particular  structure  would  tend  to  hinder 
the  refraction  of  the  Ught  rays. 

The  term  lymph  is  generally  apphed  to  that  part  of  the  body  fluid 
which  is  contained  in  the  preformed  lymphatic  channels,  while  that 
part  of  it  which  bathes  the  individual  cells,  is  designated  as  tissue 
fluid.  This  classification  has  some  points  in  its  favor,  because  the 
intercellular  spaces  are  not  always  directly  continuous  with  the  larger 
central  channels,  but  are  at  times  separated  from  them  by  delicate 
membranous  partitions.  As  the  latter  are  only  semipermeable,  it 
usually  happens  that  the  composition  of  the  tissue-fluid  is  slightly 
different  from  that  of  the  intravascular  lymph.  Lymph,  however, 
originates  in  all  parts  of  the  body  and  all  types  of  lymphatic  fluids 
contribute  toward  its  formation.  For  this  reason,  it  seems  desirable 
to  include  under  this  heading  also  those  hquids  which  are  contained 
in  the  different  serous  spaces  of  the  body,  for  example,  in  the  peri- 
cardial,  pleural  and   peritoneal   cavities,   and   in   the  spaces  of  the 

233 


234 


THE    LYMPH 


cerebrum,  spinal  cord,  eyes,  ears  and  joints.  It  should  also  be  remem- 
bered that  the  lymph  of  the  intestinal  radicles  assumes  a  milky  appear- 
ance when  much  fat  is  being  absorbed.  It  is  then  designated  as  chyle. 
The  following  fluids,  therefore,  may  be  included  in  this  discussion : 


Intercellular . 


Lymph  \ 


Intravascular . 


Tissue-fluid  throughout  the  body 
Pericardial  fluid 
Pleural  fluid 
Peritoneal  fluid 
Cerebrospinal  liquid 
Aqueous  humor 

Endo-  and  perilymph  of  the  internal  ear 
Lvmph  in  the  collecting  channels 
I  Chyle 


Properties  of  Lymph. — ^Large  quantities 
of  lymph  may  be  collected  by  inserting  a 
cannula  into  one  of  the  large  lymphatic 
channels,  preferably  the  thoracic  duct  of 
the  dog  or  cat.  The  latter  arises  in  the 
upper  part  of  the  abdominal  cavity  and 
traverses  the  chest  in  close  proximity  to 
the  descending  aorta.  It  empties  its  con- 
tents into  the  left  subclavian  vein  at  its 
point  of  confluency  with  the  external  jugular 


Fig.  119. — Thoracic  Duct. 
(D)  At  its  point  of  confluency  with  left  sub- 
clavian vein  (S);  C,  carotid  artery;  T,  trachea; 
O,  esophagus;  LC,  longus  colli  muscle;  SA, 
scalenus  anticus;  L,  lymphatic  glands;  E,  ext. 
jugular  vein. 


Fig.  120. — The  Distribution  of  the 
Lymphatics. 
A,  The  domain  of  the  thoracic  duct 
(unshaded  portion) ;  B,  right  lymph 
duct;  C,  left  cervical  duct;  D,  right 
cervical  duct. 


vein.     By  following  the  latter  into  the  aperture  of  the  chest,  a  cannula 
may  be  inserted   in  this  duct  without  rupturing   the   pleural   mem- 


PROPERTIES    AND    FORMATION    OF   LYMPH  235 

branes.  It  is  also  possible  to  tap  the  cervical  lymphatic  duct  which 
drains  the  different  structures  of  the  head.  The  thoracic  duct,  how- 
ever, is  to  be  preferred,  because  it  collects  the  lymph  from  the  largest 
part  of  the  body,  namely  from  the  posterior  extremities,  the  abdominal 
organs,  and  the  entire  left  and  lower  right  half  of  the  thorax. 

As  the  Ijnnph  is  derived  from  the  plasma  of  the  blood,  it  may  justly 
be  assumed  that  its  composition  is  very  similar  to  that  of  the  mother- 
fluid,  but  since  the  capillary  wall  really  serves  as  a  filter-like  barrier, 
the  plasma  cannot  pass  through  it  as  such  but  only  in  a  much  diluted 
form.  For  this  reason,  lymph  is  often  designated  as  diluted  plasma. 
If  gathered  during  periods  of  fasting,  it  is  as  clear  as  water,  and  only 
slightly  opalescent.  It  exhibits  a  yellowish  green  or  yellowish  gray 
hue.  Its  watery  consistency  is  indicated  by  the  fact  that  its  specific 
gravity  varies  between  1.016  and  1.023,  and  its  viscosity  between 
2400  and  3000.  It  is,  therefore,  only  1.7  times  more  viscous  than 
distilled  water  at  37°  C.^  It  possesses  a  salty  taste,  a  faint  odor,  and 
an  alkaline  reaction,  equaling  0.15-0.22  per  cent.  Na2C03.  Soon 
after  it  leaves  the  duct,  it  changes  into  a  homogeneous  jelly  and  later 
on  into  a  soft  coagulum  which  embraces  large  numbers  of  white  blood 
corpuscles  of  the  type  of  the  lymphocytes.  These  cells  seem  to  be  the 
carriers  of  the  clotting  agent,  because  their  number  bears  a  close 
relationship  to  the  mass  of  the  fibrin  formed.  The  coagulation-time 
of  lymph  varies  between  2.5  and  7  minutes,  the  average  time  being 
4.5  minutes.  It  cannot  be  said,  therefore,  that  it  clots  less  speedily 
than  blood  (dog). 

Lymph  contains  3.6  to  5.7  per  cent,  of  solids,  the  proteins  consisting  of  fibrin- 
ogen, paraglobulin,  and  serum-albumin.  When  derived  from  the  lymphatics  of 
the  liver,  it  presents  an  especially  high  percentage  of  albumin.  Its  fat  content  is 
small,  namely  0.06  per  cent.  The  salts  comprise  principally  sodium  chlorid  and 
sodium  carbonate.  Diastatic  and  lipolytic  ferments  are  also  present.  The 
following  analytical  data  have  been  furnished  by  Munk. 

Water 94 .  38-96 .  53  per  cent. 

Solids.. 3.66-  5.62  percent. 

Albumin 3 .  52-  3 .  54  per  cent. 

Reducing  substances 0 .  09-  0 .  10  per  cent. 

Minerals 

NaCl 0.583    gram  in  100  c.c.  " 

NajCOs 0.217    gram  in  100  c.c. 

K2HPO4 0.028    gram  in  100  c.c. 

CasCPOOa 0.028    gram  in  100  c.c. 

Mg3(P04)2 0.009    gram  in  100  c.c. 

Fe3(P04)2 0.0025  gram  in  100  c.c. 


0.87  per  cent. 


If  the  animal  is  fed  with  food  containing  fat,  the  lymph  traversing 
the  thoracic  duct  eventually  assumes  a  milky  appearance.  It  is  then 
known  as  chyle.  This  change  becomes  noticeable  about  2  to  3  hours 
after  the  ingestion  of  this  particular  kind  of  food  and  is  attributable 
to  the  absorption  of  globules  of  fat  which  gain  the  lymphatic  system 
through  its  intestinal  radicles,  commonly  designated  as  lacteals.     By 

^  Burton-Opitz  and  Nemser,  Am.  Jour,  of  Physiol.,  xlv,  1917,  25. 


236  THE    LYMPH 

inference  it  may  therefore  be  concluded  that  the  fat  content  of  the 
lymph  varies  directly  with  the  intensity  of  the  absorption  of  this  food- 
stuff. Thus,  it  is  not  uncommon  to  obtain  as  low  a  value  as  0.06  per 
cent,  during  fasting,  and  values  as  high  as  15  per  cent,  during  periods 
of  very  active  fat  absorption.  In  this  connection,  attention  should  be 
called  to  the  fact  that  the  lymph  does  not  aid  in  the  absorption  of  the 
proteins,  but  plays  a  part,  although  rather  insignificant,  in  the  absorp- 
tion of  sugar.  As  will  be  shown  later,  these  substances  do  not  enter 
the  lymph  but  are  transferred  in  largest  part  into  the  blood-capillaries 
of  the  intestine. 

The  microscopic  examination  of  clear  lymph  reveals  numerous 
colorless  corpuscles  belonging  to  the  group  of  the  lymphocytes. 
Rather  poor  in  cytoplasm  these  cells  display  a  prominent  nucleus. 
They  arise  in  the  lymphatic  glands  and  nodes  with  which  the  Ijonph 
channels  are  beset  and  hence  are  always  present  in  greater  numbers  in 
the  lymph  leaving  these  structures  than  in  that  entering  them.  A 
similar  difference  in  the  formed  constituents  of  the  lymph  is  noticeable 
in  lymphoid  tissues,  such  as  the  tonsils,  thjmius,  spleen,  and  the  differ- 
ent patches  and  glandular  follicles  of  the  intestine.  This  fact  clearly 
shows  that  the  organs  just  enumerated  serve  as  places  of  origin  for 
these  cells,  whence  they  are  eventually  flushed  into  the  blood-stream 
to  become  one  of  the  varieties  of  circulating  white  corpuscles. 

The  appearance  of  the  different  lymph-hke  fluids  mentioned  prev- 
iously is  very  similar  to  that  of  the  intravascular  lymph.  Normal 
cerebrospinal  fluid  is  perfectly  clear,  colorless,  slightly  salty,  and  free 
from  formed  elements.^  Its  specific  gravity  varies  between  1.002  and 
1.008;  its  reaction  is  slightly  alkaline.  Its  content  in  glucose  (0.05  to 
0.1  per  cent.)  corresponds  to  the  amounts  of  sugar  present  in  other 
serous  fluids.  Brief  reference  should  also  be  made  at  this  time  to  the 
fact  that  intracellular  glycogen  has  been  found  to  exist  in  the  cells 
of  the  choroid  plexus;^  in  fact,  it  appears  that  the  cerebrospinal  fluid 
is'a  true  secretory  product  of  this  organ.^  This  contention  is  based 
upon  the  observation  that  the  formation  of  this  fluid  may  be  acceler- 
ated by  extract  of  brain  or  retarded  by  extract  of  thyroid.  The 
cerebrospinal  liquor  does  not  coagulate  spontaneously,  because  it  does 
not  contain  fibrinogen,  but  may  be  made  to  clot  by  the  addition  of 
small  quantities  of  blood  or  lymph.  This  fact  accounts  for  the  peculiar 
phenomenon  that  this  fluid  frequently  clots  in  the  course  of  inflamma- 
tory conditions  or  after  injuries  to  the  nervous  tissue.  Obviously, 
lesions  of  this  kind  enable  the  elements  of  the  blood  to  enter  this  fluid. 
The  total  quantity  of  cerebrospinal  fluid  is  estimated  at  60  to  150  c.c. 
of  which  20  to  30  c.c.  are  contained  in  the  ventricles. 

^  Anglada,  Le  liquide  c^phalo-rachidien,  Paris,  1910  (Literature) ;  also  see :  Plaut, 
Rehm  and  Schottmiiller,  Leitf.  zur  Untersuchung  der  Zerebrosp.  Fliissigkeit.,  Jena, 
1913. 

*  Goldman,  Archiv  fiir  klin.  Chir.,  ci,  1913. 

'  Dixon  and  Halliburton,  Jour,  of  Physiol.,  xlvii,  1913,  215. 


PROPERTIES  AND  FORMATION  OF  LYMPH         237 

The  data  pertaining  to  the  humors  of  the  eye,  and  to  the  fluid  in  the 
endolymphatic  and  perilymphatic  spaces  of  the  internal  ear,  are  not 
essentially  different  from  those  just  given.  The  former  have  been 
proved  to  he  true  secretory  products  of  the  cells  covering  the  ciliary 
body.  Their  function  is  to  set  up  a  pressure  which  keeps  the  different 
constituents  of  the  eyeballs  in  a  condition  of  tension  and  thus  permits 
of  the  most  perfect  refraction  of  the  light  rays.  The  pericardial 
fluid  is  clear,  yellowish  in  color,  and  sticky  in  character.  It  contains 
2.3  to  4.5  per  cent,  of  solids  and  does  not  clot  spontaneously.  Its 
content  in  salts  (0.76  to  0.87  per  cent.)  is  made  up  largely  of  sodium 
chlorid.  The  synovial  fluid  of  the  joints  which,  however,  cannot  be 
classified  as  a  true  transudate,  possesses  in  general  the  same  composi- 
tion and  characteristics  as  the  general  lymph,  but  contains  in  addition 
an  appreciable  amount  of  mucin. 

The  Sources  of  Lymph. — Volkmann^  has  shown  at  an  early  date 
that  the  principal  constituent  of  the  body  is  water.  Upon  the  basis 
of  two-thirds  of  water  and  one-third  of  solids,  an  individual  weighing 
60  kilos  may  be  said  to  contain  40  liters  of  water;  and  furthermore, 
since  it  has  been  established  by  Starling^  that  only  about  100  c.c.  of 
lymph  are  returned  to  the  blood  in  the  course  of  one  hour  (dog),  a  very 
large  part  of  it  must  be  held  in  the  tissues.  Only  )^6  0  part  of  the  total 
quantity  of  h^mph  reenters  the  blood  in  the  time  specified. 

About  70  per  cent,  of  the  fluids  of  the  body  are  contained  in  the 
muscles,  bones  and  skin.  This  statement,  however,  does  not  imply 
that  these  structures  give  rise  to  a  proportional  amount  of  intravascular 
lymph;  indeed,  it  has  been  found  by  Starling  that  the  ductus  thoracicus 
derives  its  contents  largely  from  the  abdominal  organs  which,  under 
ordinary  conditions,  give  lodgment  to  only  about  7  per  cent,  of  the 
total  body-fluid.  Practically  no  lymph  is  returned  from  the  posterior 
extremities.  It  must  be  evident,  therefore,  that  certain  parts  of  the 
body  contain  considerable  quantities  of  fluid,  but  permit  only  a  small 
portion  of  it  to  escape  into  the  central  lymphatic  channels.  Others, 
again,  are  relatively  poor  in  fluid,  because  they  permit  a  free  through 
flow.  It  is  also  true  that  an  organ  which  gives  rise  to  large  quantities 
of  intravascular  lymph,  generally  furnishes  a  fluid  possessing  a  high 
specific  gravity.  Thus,  it  has  been  ascertained  that  the  lymph  derived 
from  the  extremities  is  very  poor  in  organic  material,  while  that  of  the 
liver  is  rich  in  these  complex  substances.  The  Ij'mph  furnished  by 
the  other  abdominal  organs,  is  not  quite  so  concentrated  as  the  latter. 

The  Formation  of  Ljmiph. — ^Lymph  is  commonly  regarded  as 
diluted  blood  plasma,  i.e.,  as  blood  plasma  which  in  its  passage  through 
the  Hning  cells  of  the  capillaries  has  lost  some  of  its  coarser  constitu- 
ents. Two  theories  are  held  regarding  its  formation.  The  oldest 
of  these  is  the  one  advocated  by  Ludwig  and  his  pupils,  and  modified 
more  recently  by  Starling.     It  holds  that  lymph  is  formed  in  a  purely 

^  Verh.  d.  sachs.  Ges.  der  Wissensch.,  Leipzig,  xxvi,  1874. 
2  Schafer's  Textbook  of  Physiology,  i,  285,  London,  1898. 


238  THE    LYMPH 

mechanical  waj-  by  the  filtration  of  the  blood  plasma  through  the  capil- 
lary wall.  The  second  theory,  propounded  by  Heidenhain  and  his 
pupils,  maintains  that  the  formation  of  lymph  is  not  effected  by 
filtration  alone,  but  is  also  dependent  upon  osmosis  and  diffusion,  and 
in  addition  upon  a  certain  vital  activity  of  the  cells.  To  the  latter 
the  term  of  vitalismus  has  been  apphed.  It  must  be  clearly  under- 
stood, however,  that  this  designation  does  not  allot  to  these  cells  meta- 
physical qualities,  but  only  intends  to  imply  that  the  formation  of 
lymph  is  associated  with  certain  microchemical  and  microphysical 
changes  which  at  this  time  are  still  beyond  scientific  analysis. 

In  accordance  with  the  pure  filtration  theory,  it  is  held  that  a  por- 
tion of  the  blood  plasma  is  forced  through  the  passive  cells  of  the 
capillary  wall  as  through  a  filter,  i.e.,  from  a  place  of  high  pressure  to 
a  place  of  low  pressure. .  The  driving  force  is  furnished  in  this  case 
by  the  pressure  prevailing  in  the  blood-capillaries,  while  the  area  of 
low  pressure  is  formed  by  the  intercellular  lymphatic  spaces.  As  no 
other  chemicophysical  force  is  brought  to  bear  upon  this  process, 
the  quantity  of  the  IjTnph  formed  must  be  directly  proportional  to 
the  capillary  pressure.  This  theor}'-  finds  support  in  the  composition 
of  the  lymph,  because  its  inorganic  constituents  are  practically  the 
same  as  those  of  the  blood  plasma,  while  its  content  in  protein  is 
considerably  less. 

It  also  finds  some  support  in  certain  observations  to  which  atten- 
tion has  been  called  by  Starhng.  Thus,  it  has  been  found  that  while 
the  quantity  of  Ijonph  is  usually  directly  proportional  to  the  height 
of  the  capillary  pressure,  it  does  not  preserve  this  relationship  at  all 
times.  This  fact  tends  to  show  that  a  relatively  low  blood  pressure 
may  be  associated  with  a  very  copious  secretion,  and  vice  versa.  At  all 
events,  these  results  are  not  in  accordance  with  the  conditions  neces- 
sary for  filtration.  This  author  also  claims  that  the  permeabihty  of 
the  capillary  endothehum  is  not  the  same  in  all  parts  of  the  body. 
Thus,  it  is  stated  that  the  walls  of  the  capillaries  traversing  connective 
tissue,  ofifer  a  much  greater  resistance  to  the  escaping  lymph  than 
those  of  the  intestine  and  liver.  The  latter,  in  fact,  are  surprisingly 
permeable.  In  harmony  with  these  structural  and  functional  differ- 
ences, it  has  been  found  that  the  Ijonph  derived  from  the  former  is 
usually  very  dilute,  while  that  from  the  aforesaid  abdominal  organs 
contains  a  very  appreciable  amount  of  proteins.  The  greatest  pos- 
sible permeabihty  is  shown  by  the  capillaries  of  the  hver,  in  which 
organ  a  copious  transudation  of  concentrated  Ij-mph  is  frequently 
associated  with  very  low  pressures.  In  this  connection  it  is  of  interest 
to  note  that  the  fining  of  the  hepatic  capillaries  is  in  many  places  very 
incomplete,  so  that  the  blood  is  enabled  to  come  into  much  closer 
contact  with  the  liver-ceUs.  For  this  reason,  it  cannot  surprise  us  to 
find  that  a  fiuid  which  is  injected  into  the  arterial  supply  channels  of 
this  organ,  frequently  escapes  into  the  spaces  between  the  hepatic 
cells. 


PROPERTIES    AND    FORMATION    OF   LYMPH  239 

The  influence  which  the  capillary  blood  pressure  possesses  upon 
the  production  of  lymph,  may  be  more  fully  portrayed  in  the  follow- 
ing manner.  If  the  lymphatics  of  the  liver  are  ligated,  the  largest 
part  of  the  Ij^mph  traversing  the  thoracic  duct,  must  of  course  be  de- 
rived from  the  intestines.  If  the  thoracic  aorta  is  now  obstructed,  the 
flow  of  lymph  ceases,  owing  to  the  diminished  capillary  pressure. 
Just  the  opposite  effect,  namely,  a  heightened  driving  force  and  an 
increased  discharge  of  lymph,  may  be  obtained  by  obstructing  the 
portal  vein.  A  similar  experiment  may  be  performed  upon  the  liver 
itself.  If  the  inferior  vena  cava  is  compressed  centrally  to  the  orifice 
of  the  hepatic  vein,  a  pronounced  diminution  of  the  general  blood 
pressure  results  which,  however,  is  accompanied  by  an  increase  in  the 
flow  of  the  lymph  from  the  thoracic  duct.  In  view  of  the  fact  that  the 
obstruction  of  the  vena  cava  leads  to  an  engorgement  of  the  blood- 
vessels of  the  liver  and  a  local  rise  in  the  capillary  pressure,  this  result 
cannot  surprise  us,  and  especially  not  if  it  is  noted  that  the  occlusion 
of  the  hepatic  vein  remains  without  effect,  provided  that  the  lymphatics 
of  this  organ  have  been  hgated  beforehand.  An  augmentation  of  the 
capillary  pressure  of  the  posterior  extremities  may  be  produced  in  an 
easy  way  by  blocking  the  venous  return,  but,  curiously  enough,  this 
procedure  does  not  materially  increase  the  flow  of  lymph  from  this 
particular  part  of  the  body.  Starling  endeavors  to  unify  these  data 
by  assuming  that  the  height  of  the  pressure  plays  a  paramount  role 
in  the  formation  of  lymph  only  in  those  organs  in  which  the  capil- 
laries are  very  permeable,  while  in  those  organs  in  which  they  are  rela- 
tively impermeable,  other  factors  are  brought  into  play. 

The  view  of  Heidenhain  is  based  upon  a  number  of  facts  which, 
however,  do  not  deny  that  filtration  plays  a  part  but  merely  tend  to 
prove  that  this  factor  is  not  the  only  one  concerned  in  the  formation 
of  lymph.  This  author  shows  first  of  all  that  the  different  organs  are 
quite  unable  to  derive  their  entire  supply  of  inorganic  and  organic 
material  from  lymph  which  is  formed  exclusively  by  filtration,  because 
a  quantity  of  fluid  would  be  required  to  satisfy  their  needs  which  would 
be  very  much  larger  than  that  actually  present  in  our  body.  For 
example,  as  1.7  grams  of  CaO  are  contained  in  1.0  kg.  of  cow's  milk, 
the  entire  product  for  24  hours  would  embrace  about  42.5  grams  of 
this  substance.  In  order  to  render  this  amount  available  to  the  secre- 
tory cells  of  the  mammary  glands,  236  liters  of  lymph  would  be 
required,  because  this  substance  is  normally  present  in  a  concentra- 
tion of  only  0.018  per  cent.  This  discrepancy  can  only  be  explained 
by  assuming  that  the  filtration  is  associated  with  osmosis  and  diffusion 
which  processes  would  naturally  tend  to  augment  that  production  of 
lymph  which  is  had  by  pressure  alone. 

Heidenhain  has  also  called  attention  to  the  fact  that  the  increases 
in  the  flow  of  lymph  are  not  always  associated  with  rises  in  the  capil- 
lary blood  pressure.  In  testing  the  influence  which  the  exclusion  of 
different  tissues  and  organs  exerts  upon  the  lymph  flow,  it  was  found 


240  THE    LYMPH 

that  the  ligation  of  the  hepatic  vein  is  followed  bj^  an  increased  forma- 
tion of  lymph  rich  in  proteins.  This  fact  has  been  interpreted  by  this 
author  as  sho^\ing  that  the  lining  cells  of  the  hepatic  capillaries  possess 
a  true  secretory  power.  Starling,  on  the  other  hand,  came  to  the  con- 
clusion later  on  that  it  is  due  to  the  greater  permeability  of  these 
channels  occasioned  by  a  certain  structural  deficiency  of  their  lining. 
This  diversity  of  opinion,  however,  does  not  lessen  the  weightiness 
of  the  observations  of  Heidenhain,  because  while  it  is  possible  to  in- 
terpret this  phenomenon  in  this  way,  a  single  exception  of  this  kind 
does  not  materially  weaken  the  sum  total  of  the  evidence  presented. 

Undoubtedly  the  most  important  facts  brought  forth  by  Heiden- 
hain pertain  to  the  augmentation  of  the  lymph  flow  by  means  of  sub- 
stances which  he  has  designated  as  hmiphagogues.  But,  as  these 
agents  not  only  accelerate  the  production  of  lymph,  but  also  give  rise 
to  Ijmiph  of  a  different  concentration,  they  have  been  divided  into 
IjTnphagogues  of  the  first  and  second  class.  To  the  former  group 
belong  watery  extracts  of  the  dried  muscles  of  crabs,  crayfish  and 
leeches,  the  products  of  certain  bacteria,  extracts  of  liver  and  intestine, 
peptone  and  egg  albumin.  In  the  second  gi-oup  must  be  placed  all 
crystahne  substances,  such  as  sugar,  sodium  chlorid  and  other  neutral 
salts. 

On  injecting  a  hmiphagogue  of  the  first  class  into  the  venous 
circulation,  the  flow  of  lymph  is  increased  as  much  as  six  times  the 
normal.  This  quantitative  change  is  associated  with  a  greater  concen- 
tration and  a  lessened  coagulability  of  the  lymph,  and  may  be  obtained 
with  very  small  amounts  of  the  excitatory  substance.  The  blood 
pressure,  therefore,  suffers  no  change  whatever,  and  hence,  this  result 
cannot  justly  be  attributed  to  an  enhancement  of  the  conditions  of 
filtration.  An  even  greater  discharge  of  lymph  may  be  obtained  with 
the  help  of  the  lymphagogues  of  the  second  class,  but  naturally,  as  the 
introduction  of  these  substances  necessitates  a  solvent,  it  cannot  be 
avoided  that  the  plasma  of  the  blood  and  the  body-fluid  are  thereby 
rendered  more  watery.  It  is  possible,  however,  to  complete  these 
injections  without  markedly  increasing  the  general  blood  pressure, 
provided  that  the  solution  is  permitted  to  enter  slowly.  It  seems, 
therefore,  that  the  careful  introduction  of  moderate  amounts  of  water 
as  solvent  cannot  be  seriousl}"  objected  to,  because  it  is  not  hkely  to 
augment  the  capillary  pressure  in  a  measure  sufficient  to  be  able  to 
refer  the  increased  flow  of  l^Tnph  to  this  cause. 

Great  importance  has  been  attached  to  the  fact  that  the  flow  of 
lymph  continues  for  some  time  after  death,  and  may  even  be  height- 
ened at  this  time  by  the  injection  of  a  IjTnphagogue.  Strictly  speaking, 
however,  this  phenomenon  does  not  actually  prove  that  lymph  is 
formed  after  the  blood  has  ceased  to  circulate,  because  it  is  quite  pro- 
bable that  the  tissue-fluid  continues  to  seek  the  large  lymphatics  even 
after  the  capillary  pressure  has  been  destroyed.  Stress  has  also  been 
placed  upon  the  fact  that  post-mortem  lymph  possesses  a  greater  con- 


PROPERTIES    AND    FORMATION    OF    LYMPH  241 

ccntration  than  normal  lymph.  It  must  be  admitted,  however,  that 
this  change  may  be  caused  by  a  rapid  influx  of  the  "blood  plasma" 
from  the  liver  capillaries. 

The  view  of  Heidenhain,  that  the  lymi)hafi;()fj;ucs  exert  their  char- 
acteristic action  by  stimulating  the  cells  of  the  capillary  walls  to 
greater  activity,  has  been  objected  to  by  Starling,  upon  the  ground  that 
the  lymphagogues  of  the  first  class  injure  the  lining  cells  of  the  blood- 
vessels, and  especially  those  of  tlie  liver.  Henc{;  tlujy  permit  a  greater 
through  flow  of  concentrated  lymph  simply  by  ))eing  more  permeable. 
The  lymphagogues  of  the  second  group  are  said  by  him  to  render  the 
lymph  hypertonic,  thereby  equipping  it  with  a  greater  osmotic  pres- 
sure. In  consequence  of  this  change  the  tissue-fluid  is  drawn  into  the 
larger  lymphatics  and  eventually  finds  its  way  into  the  blood-stream. 
Priority,  however,  cannot  be  accorded  to  this  statement,  because  Hei- 
denhain has  shown  at  an  even  earlier  date  that  the  lymph-driving  prop- 
erties of  these  substances  are  proportional  to  thc^ir  osmotic  power. 
Ascher^  and  his  pupils  regard  the  lymphagogues  of  the  first  class  as 
liver-poisons  which  not  only  tend  to  increase  the  formation  of  lymph, 
but  also  accelerate  the  other  activities  of  this  organ.  Thus,  it  has 
been  demonstrated  that  chemical  and  morphological  changes,  such  as  a 
disappearance  of  the  glycogen,  result  whenever  these  substances  are 
injected.  In  a  similar  manner,  Popoff-  has  shown  that  the  introduc- 
tion of  peptone  increases  the  flow  of  lymph  from  the  thoracic  duct,  but 
does  not  augment  the  flow  from  other  channels.  This  result  is  easily 
explained,  because  this  extra  quantity  of  lymph  is  derived  principally 
from  the  intestine.  It  has  also  been  noted  that  the  peptone  gives  rise 
to  a  hyperemic  condition  of  the  portal  blood-vessels  which  eventually 
culminates  in  hemorrhagic  extravasations  into  the  intestinal  wall. 

As  the  average  student  of  physiology  is  largely  concerned  with  the 
acquisition  of  definite  fundamental  facts  and  cannot  be  expected  to 
display  a  keen  interest  in  controversial  discussions,  it  seems  best  not 
to  debate  this  question  further.  Suffice  to  say,  that  we  are  in  posses- 
sion of  certain  agents  which  give  rise  to  a  greater  formation  of  lymph 
without  causing  significant  alterations  in  either  the  general  or  the  local 
blood  pressure.  Clearly,  if  the  dynamical  conditions  in  the  capillaries 
are  permitted  to  remain  the  same,  while  at  the  same  time  a  more 
copious  discharge  of  lymph  is  obtained,  it  may  justly  be  assumed  that 
this  result  is  dependent  upon  a  greater  activity  of  the  lining  cells  of  the 
capillaries.  In  accordance  with  the  conception  of  Heidenhain,  these 
cells  may  therefore  be  said  to  be  equipped  with  true  secretory  powers. 
But  even  if  the  reader  should  feel  inclined  to  favor  the  view  that  these 
phenomena  do  not  necessitate  the  assumption  of  a  vital  activity  on  the 
part  of  the  fining  cells,  the  filtration  theory  would  nevertheless  have 
to  be  greatly  modified,  because  we  are  still  in  a  position  to  cite  other 
data  in  opposition  to  it. 

'  Zeitschr.  ftir  Biologie,  xxxii-xlvii,  1895-1906. 
2  Jour,  of  Physiol.,  xxv,  1899,  479. 
16 


242  THE    LYMPH 

It  is  a  well-known  fact  that  the  stimulation  of  the  choida  tympani 
nerve  is  followed  by  a  dilatation  of  the  blood-vessels  of  the  submaxillary 
gland  and  a  copious  discharge  of  saliva.  This  effect  is  not  obtained 
subsequent  to  the  administration  of  atropin.  Concerning  the  dis- 
charge of  lymph,  it  has  been  found  by  Heidenhain  and  Cohnheim^ 
that  the  excitation  of  this  nerve  causes  no  alteration,  in  spite  of  the 
fact  that  the  vascularity  of  this  organ  is  very  much  increased.  Fur- 
thermore, it  has  been  observed  by  Barcroft^  that  the  water  lost  by  the 
blood  during  its  passage  through  this  gland,  enters  not  only  the 
sahvary  ducts,  but  also  finds  its  way  in  even  greater  quantities  into 
the  lymphatics.  In  this  connection,  it  should  also  be  mentioned  that 
Ascher  and  his  co-workers  have  proved  that  other  organs,  such  as  the 
thyroids,  intestine,  liver,  and  pancreas,  give  rise  to  much  greater 
amounts  of  lymph  whenever  their  activity  is  heightened,  and  that  the 
lymph  formed  during  these  periods  of  increased  metabolism  is  more 
concentrated.  In  explanation  of  these  phenomena  it  is  possible  to 
submit  three  views,  namely,  (a)  that  any  glandular  activity  leads  to 
the  production  of  certain  substances  which  tend  to  stimulate  the  lining 
cells  of  the  capillaries  (Heidenhain),  (h)  that  lymph  may  also  be  formed 
by  the  secretory  cells  of  these  glands  (Ascher),  and  (c)  that  the  complex 
molecules  of  the  proteins,  fats  and  carbohydrates  are  simplified  so  that 
the  number  of  the  particles  in  solution  in  the  lymph  is  increased  in 
harmony  with  the  increase  in  the  osmotic  pressure  of  the  latter 
(StarHng). 

The  third  view  has  also  been  offered  by  Starling  and  others  in 
explanation  of  the  fact  that  the  intravascular  lymph  and  tissue-fluid 
possess  a  greater  molecular  concentration  than  the  blood. ^  As  has 
been  stated  previously,  it  is  beheved  that  the  disintegration  of  the 
complex  molecules  renders  the  lymph  hypertonic  and  that  this  cata- 
bolic  change  then  leads  to  an  influx  of  water  into  the  lymphatics. 
On  close  examination,  however,  this  explanation  cannot  be  considered 
as  a  very  good  one,  because  it  is  known  that  the  vascular  walls  are 
very  permeable  to  water,  and  hence,  it  seems  quite  unlikely  that  the 
osmotic  differences  between  the  blood  and  the  tissues  can  be  main- 
tained for  any  length  of  time.  For  this  reason,  it  is  safe  to  assame 
that  the  greater  molecular  concentration  of  the  lymph  can  only  be 
retained  with  the  aid  of  some  special  activity  of  the  lining  cells  of 
the  capillaries. 

In  this  connection,  mention  should  also  be  made  of  the  experiments 
of  Heinecke  and  Megerstein*  which  Show  that  the  sodium  chlorid 
content  of  the  blood-serum  of  nephritic  rabbits  is  less  than  that  of  the 
ascitic  fluid.  Moreover,  if  this  salt  is  ingested  in  larger  amounts,  the 
percentage  of  this  salt  increases  in  the  serum  as  well  as  in  the  transu- 

1  Vorles.  iiber  allg.  Pathologie,  2,  Ausgabe,  i,  1882,  493. 

2  Jour,  of  Physiol.,  xxv,  1899,  479. 

3  Botazzi,  Ergebn.  der  Physiol.,  vii,  1908,  310. 
*  Archiv  fiir  klin.  Med.,  xc,  1907,  101. 


PROPERTIES    AND    FORMATION    OF    LYMPH  243 

date,  but  in  a  more  uninistakal:)le  manner  in  the  latter.  This  result 
proves  very  clearly  that  the  capillary  wall  possesses  a  certain  selective 
power  which  enables  it  to  keep  the  NaCl-contcnt  of  the  blood  constant 
by  facilitating  the  escape  of  the  superfluous  quantity  of  this  salt.  That 
the  lining  cells  are  also  capable  of  furthering  the  escape  of  water  has 
•been  demonstrated  by  the  experhnents  of  Carlson,  Greer  and  Becht.^ 
It  seems  that  the  lymph  in  the  cervical  ducts  of  the  horse  or  dog  may 
acquire  a  molecular  concentration  much  below  that  of  the  blood; 
in  fact,  the  difference  may  become  so  great  at  times  that  it  cannot  be 
explained  upon  the  basis  of  ordinary  hydrostatic  laws.  The  secretory 
properties  of  the  capillary  lining  cells  are  also  proved  in  an  indirect 
way  by  the  fact  that  the  cellular  components  of  the  salivary  glands, 
kidneys  and  pancreas  completely  dominate  the  quantity  and  quaUty 
of  their  respective  secretions.  If  this  power  is  conceded  to  one  group 
of  cells,  it  would  be  difficult  to  deny  it  to  other  groups  of  cells.  An 
impartial  consideration  of  the  evidence,  therefore,  must  lead  us  to  con- 
clude that  the  formation  of  lymph  is  dependent  upon  (a)  differences  in 
pressure  between  the  blood  and  lymph  spaces,  (6)  differences  in  the 
concentration  of  the  body  fluids,  and  (c)  true  secretory  properties  on 
the  part  of  the  cells  forming  the  capillary  walls.  Thus,  the  three  fac- 
tors engaged  in  this  process  are:  filtration,  diffusion  and  osmosis  and  a 
vital  activity  of  the  capillary  cells. 

The  Factors  Controlling  the  Flow  of  Lymph. — It  has  been  stated 
above  that  the  lymph  is  formed  among  the  cells  of  the  different 
tissues  and  that  it  moves  from  here  with  varying  rapidity  into  the 
larger  collecting  channels,  whence  it  again  reaches  the  vascular  system. 
The  plasma  thus  temporarily  diverted  at  the  periphery  into  extra- 
vascular  spaces,  is  eventually  returned  to  the  blood  traversing  the  cen- 
tral circulatory  system.  A  picture,  the  impressiveness  of  which 
can  scarcely  be  surpassed,  is  presented  at  the  point  of  confluency 
between  the  thoracic  duct  and  the  left  subclavian  vein.  The  clear 
lymph  intermingles  here  with  the  dark  venous  blood  in  the  manner 
of  two  rivers  carrying  varying  amounts  of  sedimentous  material. 
This  picture  is  especially  fascinating  about  two  hours  after  the  inges- 
tion of  fatty  food,  i.e.,  after  the  lymph  has  assumed  a  milky  appearance 
in  consequence  of  its  high  molecular  content  in  fat.  The  entire  duct 
is  then  sharply  outhned  and  may  be  followed  to  the  receptaculum 
chyU  and  its  tributary  radicles  upon  the  surfaces  of  the  intestine. 
The  discussion  pertaining  to  this  subject  may  be  arranged  as  follows: 

1.  While  the  pressure  under  which  the  lymph  is  retained  in  the  smallest  chan- 
nels amounts  to  only  10  to  15  mm.  H2O,  it  nevertheless  decreases  steadily  in  the 
direction  from  the  tissues  to  the  orifices  of  the  main  lymphatic  ducts.  Lymph  is 
formed  peripherally  under  a  capillary  blood  pressure  which  may  be  reckoned  at 
about  40  mm.  Hg.,  while  the  pressure  encountered  in  the  central  venous  trunks 
amounts  to  —  5  mm.  Hg.^  Lymph,  therefore,  flows  from  a  place  of  high  pressure 
to  a  place  of  low  pressure,  but  the  decline  is  not  equally  rapid  in  all  parts  of  the 

1  Am.  Jour,  of  Physiol.,  xix,  1907,  360. 

2  Burton-Opitz,  Am.  Jour,  of  Physiol.,  ix,  1903,  198. 


244  THE    LYMPH 

lymphatic  system.  No  doubt,  the  greatest  part  of  the  original  driving  force  is  used 
up  in  its  passage  through  the  lining  cells  of  the  capillaries,  because  the  pressure 
in  the  tissue  spaces  is  very  slight.  Scarcely  10  mm.  Hg  are  left  for  the  return  of 
the  lymph  from  the  tissue  to  the  blood-stream. 

2.  The  structure  of  the  lymphatic  tubules  is  very  similar  to  that  of  the  blood- 
capillaries.  Their  walls  are  composed  of  a  single  layer  of  elongated  cells  with 
sinuous  outlines  which  are  joined  at  their  edges  into  delicate  tubules.  While  the 
small  lymphatic  ducts  are  generally  larger  than  the  blood-capillaries,  they  do  not 
retain  a  constant  diameter  throughout,  because  constrictions  are  formed  here  and 
there  which  impart  a  segmented  or  bead-like  appearance  to  the  entire  channel. 
The  diameter  of  the  thoracic  duct,  for  example,  varies  between  8  mm.  and  4  mm. 
Of  greatest  importance  to  us  at  this  time  is  the  fact  that  these  narrow  places  are 
usually  beset  with  streamer-like  valves  which  open  only  in  the  direction  of  the 
venous  channels  and  close  as  soon  as  the  pressure  in  the  more  central  lymphatic  rises 
above  that  in  its  tributaries.  In  this  way,  a  backward  flow  of  lymph  is  prevented. 
3.  The  flow  of  lymph  is  also  furthered  by  the  contractions  of  the  skeletal  mus- 
culature. Under  ordinary  conditions,  practically  no  lymph  escapes  from  the  rest- 
ing limbs,  while  copious  amounts  of  it  are  derived  from  the  abdominal  lymphatics. 


Fig.   121. — Cross-section  of  Lymphatic   Vessel  to  Show  Arrangement  of  Valves. 

The  muscles,  however,  are  well  supplied  with  fluid  so  that  their  contraction  is 
immediately  followed  by  an  appreciable  discharge  of  lymph.  Quite  naturally,  as 
the  lymphatics  are  equipped  with  valves,  the  pressure  which  is  thus  brought  to 
bear  upon  their  outside  surfaces,  must  effect  a  quick  onward  rush  of  lymph  in  the 
direction  of  the  more  central  ducts.  The  respiratory  movements  also  facilitate 
the  onward  movement  of  lymph  in  an  indirect  way,  because  during  inspiration  the 
intraabdominal  pressure  is  increased,  while  the  intrathoracic  pressure  is  decreased. 

4.  The  importance  of  gravity  as  a  factor  favoring  the  flow  of  lymph  varies 
with  the  position  of  the  body.  Under  normal  conditions,  this  force  cannot  exert 
an  unfavorable  influence  upon  dependent  parts,  for  the  same  reason  that  it  cannot 
hinder  the  flow  of  the  blood.  The  lymphatics  possess  a  certain  degree  of  tonicity 
which  tends  to  counteract  the  effects  of  gravity. 

5.  In  amphibia,  reptilia  and  birds,  the  flow  of  the  lymph  is  also  aided  by  lymph- 
hearts  which  contract  rhythmically  at  the  rate  of  about  fifty  beats  in  a  minute. 
These  pulsating  saccules  receive  several  lymphatics  and  give  off  a  single  tube 
which  in  most  cases  is  directly  connected  with  a  blood-vessel.  The  orifices  of  the 
tributary  tubules,  as  well  as  that  of  the  central  channel,  are  guarded  by  valves  which 
insure  a  flow  in  the  direction  from  the  tissues  toward  the  veins.  In  the  frog,  the 
pulsations  of  the  lymph-hearts  may  be  observed  dorsally  in  the  fore  part  of  the 
body  as  well  as  next  to  the  coccyx. 


SECTION  V! 
RESISTANCE  AND  IMMUNITY 

CHAPTER  XXII 
THE  BLOOD  AND  LYMPH  AS  PROTECTIVE  MECHANISMS' 

General  Consideration. — The  phenomena  of  resistance  and 
immunity  may  justly  be  regarded  as  belonging  to  physiology,  because 
the  protection  afforded  an  animal  against  toxic  influences  of  all  kinds, 
finds  its  origin  in  certain  agents  which  are  generated  by  the  components 
of  its  tissues.  In  a  practical  way,  however,  the  subject  of  immunity 
is  more  intimately  related  to  bacteriology,  and  hence,  it  is  intended  to 
restrict  the  present  discussion  to  the  most  essential  general  facts. 

The  body  of  an  animal  is  protected  in  a  certain  measure  against 
various  poisonous  substances,  albuminous  material,  ferments,  cellular 
products,  and  pathogenic  bacteria  and  their  derivatives.  When  fully 
developed,  a  resistance  of  this  kind  constitutes  an  immunity.  Thus, 
an  animal  which  cannot  be  affected  by  an  ordinary  dose  of  a  certain 
toxic  substance,  is  said  to  be  immune  against  it.  This  resistance, 
however,  may  not  be  sufficient  against  larger  doses  of  the  same  poison, 
nor  against  minimal  doses  of  an  unusually  virulent  toxin.  Moreover, 
the  degree  of  immunity  may  be  varied  by  outside  influences  so  that 
periods  of  resistance  alternate  with  periods  of  susceptibility. 

Immunity  may  be  partial  or  covi'plete,  but  the  absolute  type  is  rather 
uncommon.  Thus,  cold-blooded  animals  are  often  quite  insusceptible 
to  many  of  the  bacteria  which  produce  violent  reactions  in  warm- 
blooded animals,  while  many  of  the  latter  are  thoroughly  protected 
against  the  infections  which  the  lower  forms  are  very  prone  to  incur. 
As  far  as  man  is  concerned,  an  immunity  may  be  restricted  to  (a)  all 
individuals,  (&)  certain  races  or  tribes,  (c)  certain  families,  and  {d)  cer- 
tain persons.  For  example,  such  diseases  as  Texas  fever  or  hog  cholera 
are  not  prevalent  among  mankind,  while  yellow  fever  and  malaria  do 
not  usually  attack  the  negroes  of  the  West  Indies.  Quite  similarly, 
certain  families  or  individuals  may  possess  a  degree  of  resistance 
against  tuberculosis  which  is  not  shown  by  others. 

Like  other  biological  characteristics,  the  power  of  resisting  a 
specific  pathogenic  influence  may  be  propagated  from  parent  to  off- 

^A  more  detailed  account  will  be  found  in  Wassermann's  "Immune  sera, 
hemolysins,  cytotoxins  and  precipitins,"  translated  by  Bolduan,  New  York,  1904. 

245 


246  RESISTANCE    AND    IMMUNITY 

spring,  or  may  be  acquired  either  by  an  accidental  or  an  experimental 
infection.  In  the  former  instance,  the  immunity  is  said  to  be  natural 
or  inherited  and,  in  the  latter,  acquired.  The  acquired  type  is  specific 
in  its  nature,  i.e.,  it  protects  solely  against  a  particular  kind  of  toxic 
agent,  and  not  against  others.  Thus,  it  is  possible  to  develop  a  resist- 
ance against  the  bacillus  of  diphtheria,  while  at  the  same  time  the  body 
remains  open  to  infections  by  other  germs,  such  as  the  bacillus  of  teta- 
nus or  typhoid.  Moreover,  while  the  inherited  immunity  is  generally 
permanent,  the  acquired  type  is  often  only  tem-porary,  enabling  the  same 
germ  to  invade  that  anunal  a  second  time.  It  is  true,  however,  that 
most  of  the  infectious  diseases,  such  as  typhoid,  diphtheria,  yellow 
fever,  small-pox,  scarlet  fever,  and  others,  occur  as  a  rule  only  once  in 
the  same  individual.  Immunity  is  also  characterized  as  general  and 
local,  the  former  designation  imph'ing  that  the  cells  of  the  body  as  a 
whole  are  affected,  and  the  latter,  that  solely  a  particular  tissue 
is  so  favored.  For  example,  it  is  a  well-known  fact  that  the  Peyer's 
patches  of  the  intestine  do  not  offer  favorable  conditions  for  the  growth 
of  the  typhoid  bacillus  if  they  have  already  served  as  the  seat  of  a 
proliferation  of  this  kind. 

Active  immunity  is  the  resistance  which  is  acquired  by  an  animal 
in  the  course  of  an  active  unmunization.  Various  methods  are 
practised  to  render  an  animal  immune  in  this  manner,  but  all  of  them 
purpose  to  stimulate  the  tissues  so  that  they  take  an  active  part  in  the 
development  of  the  resistance.  This  end  may  be  attained  (a)  with 
attenuated  cultures,  (6)  vnih.  sublethal  doses  of  virulent  bacteria, 
(c)  with  dead  bacteria,  {d)  with  the  products  of  the  bacteria  prepared 
from  filtered  cultures,  and  (e)  by  feeding  the  dead  cultures. 

Passive  immunity  is  the  resistance  conferred  upon  an  animal  by 
introducing  into  its  system  certain  immune  agents  which  have  been 
developed  in  another  animal  in  the  course  of  an  active  immunization. 
This  procedure,  which  promises  important  therapeutic  results,  dates 
from  the  time  of  Behring  (1890),  who  showed  that  the  sera  of 
animals  immunized  against  the  products  of  the  tetanus  or  diphtheria 
bacillus,  may  be  introduced  into  other  animals  with  the  result  that  the 
recipients  are  rendered  resistant  against  these  particular  poisons. 
This  type  of  immunity,  therefore,  is  conferred  upon  an  animal  without 
it  actively  participating  in  this  process  of  forming  those  elements  w^hich 
are  responsible  for  the  resistance.  The  sera  employed  in  this  process 
are  known  as  antitoxic  sera,  and  are  said  to  contain  antitoxins,  or  bodies 
which  are  specifically  antagonistic  to  toxins. 

In  illustration  of  passive  immunization  might  be  mentioned  the 
procedure  usually  followed  in  protecting  human  beings  against  the 
toxins  of  the  diphtheria  bacillus.  The  antitoxin  concerned  in  this 
reaction  is  obtained  in  larger  quantities  wdth  the  help  of  young  and 
vigorous  horses.  The  systems  of  these  animals  is  first  accustomed  to 
the  diphtheria  poison  by  the  subcutaneous  administration  of  small 
doses  of  diphtheria  toxin.     The  doses  are  then  gradually  increased. 


THE  BLOOD  AND  LYMPH  AS  PROTECTIVE  MECHANISMS       247 

At  the  end  of  three  or  four  months  a  quantity  of  blood  is  withdrawn 
from  the  jugular  vein  under  antiseptic  precautions,  and  is  allowed  to 
clot.  Its  serum  is  then  treated  in  a  special  way  and  is  finally  standard- 
ized. Under  favorable  conditions,  an  animal  yields  from  250  to  800 
units  of  antitoxin.  For  the  prophylactic  immunization  of  healthy 
individuals  about  500  units  are  required,  while  in  a  therapeutic  way, 
it  may  be  administered  in  amounts  ranging  between  3000  and  20,000 
units. 

Causes  of  Immunity. — In  general  it  may  be  stated  that  the  immu- 
nity against  microbic  infection  is  dependent  upon  two  processes,  namely, 
upon  the  phagocytic  power  of  the  leukocytes,  in  the  presence  of 
opsonins  (page  203),  and  secondly,  upon  the  protecting  influence  of 
certain  substances,  known  as  antibodies.  As  perfectly  definite  histo- 
logical elements  have  not  been  discovered  as  yet  in  the  fluids  of  our 
body,  these  antibodies  must  be  regarded  as  the  products  of  precise 
chemical  correlations,  i.e.,  as  agents  that  have  been  developed  in  the 
course  of  physicochemical  reactions  between  the  cellular  components 
of  the  tissues  and  the  invading  unit,  or  antigen.  Thus,  the  effective- 
ness of  an  immunity  must  depend  upon  the  quantity  and  quality  of 
the  antibodies  which  are  formed  in  consequence  of  the  stimulating 
action  of  the  antigen. 

The  place  of  origin  of  these  bodies  has  not  been  definitely  ascer- 
tained. It  is  believed  by  some  investigators  that  they  are  generated 
somewhere  in  the  body  in  the  course  of  tissue  metabolism,  while  others 
hold  that  they  are  not  independent  elements  but  are  derived  from  the 
leukocytes.  If  the  latter  view  is  accepted,  which  is  that  of  the  French 
school,  the  entire  process  of  immunity  constitutes  merely  a  reaction 
which  is  secondary  to  phagocytosis.  The  facts  brought  forth  by 
Ehrlich  and  his  pupils,  however,  seem  to  contradict  this  conception. 
Thus,  it  has  been  found  that  the  immune  bodies  exist  preeminently 
in  the  blood,  but  their  presence  can  only  be  established  in  a  physio- 
logical way.  In  illustration  of  this  statement  it  might  be  mentioned 
that  the  destructive  power  of  sera  upon  bacteria  is  lessened  by  allowing 
them  to  stand,  or  by  heating  them  to  56°  C.  It  has  also  been  observed 
repeatedly  that  immunized  blood-serum  is  richer  in  globulin  than  nor- 
mal serum. 

Many  physiological  facts  might  be  cited  to  prove  that  an  animal 
is  in  actual  possession  of  these  antibodies  and  that  it  is  equipped  with 
them  either  at  birth,  or  later  on  in  the  course  of  its  life.  It  is  also  of 
interest  to  note  that  the  formation  of  these  bodies  may  be  brought 
about  not  only  with  the  aid  of  bacteria  and  their  products,  but  also 
with  the  help  of  a  number  of  different  toxins  of  animal  and  vegetable 
origin.  Ehrlich,^  for  example,  has  shown  that  specific  antitoxins  may 
be  formed  against  the  poisons  of  some  of  the  higher  plants.  Similar 
protective  substances  have  been  obtained  by  Galmette^  against  the 

^  Deutsch.  med.  Wochenschr.,  1891. 
2  Compt.  rend.,  1894. 


248  EESISTANCE    AND    IMMUNITY 

venoms  of  snakes;  moreover,  Bordet,^  as  well  as  Belfanti  and  Carbone,^ 
have  established  the  fact  that  the  serum  of  an  animal  into  which  the 
defibrinated  blood  of  another  species  has  been  repeatedly  injected, 
acquires  the  power  of  hemolyzing  the  red  cells  of  this  serum.  Quite 
similarly,  the  repeated  injection  of  spermatozoa^  may  finally  lead  to 
the  production  of  a  blood-serum  which  acts  destructively  upon 
these  elements.  Reactions  of  varying  specificity  have  also  been 
obtained  with  ciliated  epithelium,  mucous  tissue,  pancreas,  and 
kidney  substance. 

*  In  general  it  may  be  said  that  the  blood  and  tissue-fluids  are  capable 
of  inciting  any  one  of  the  following  reactions : 

(a)  A  destruction  of  red  corpuscles,  hemolysis. 

(6)  A  destruction  of  other  types  of  cells,  cytolysis. 

(c)  A  destruction  of  bacterial  cells,  bacteriolysis. 

(d)  An  agglutination  or  clumping  of  cells  of  different  kinds,  inclu- 
sive of  bacteria. 

(e)  A  precipitation  of  the  cytoplasm. 

(/)  A  coagulation  of  the  cellular  contents. 

The  substances  by  means  of  which  these  reactions  are  brought 
about,  are  designated  respectively  as  hemolysins,  cytolysins,  bacteri- 
olysins,  agglutinins,  precipitins,  and  coagulins,  but  only  the  last  four 
of  these  plaj^  a  part  in  the  production  of  that  tj^pe  of  immunity  which 
is  specifically  directed  against  pathogenic  bacteria. 

Nature  of  the  Reaction. — Two  theories  are  commonly  held  to 
explain  bacterial  immunity.  Thus,  it  has  been  suggested  by  Roux, 
Buchner,  and  others  that  the  antitoxic  substances  or  antitoxins  do 
not  attack  the  toxins  directly,  but  destro}^  them  in  an  indirect  way 
by  rendering  the  bod}"  more  resistant  against  them.  In  the  second 
place,  it  has  been  proposed  by  Ehrhch,  Behring  and  others  that  a 
specific  interaction  occurs  between  the  antitoxin  and  the  toxin  in  the 
nature  of  an  ordinary  chemical  reaction.  The  evidence  so  far  pre- 
sented b}"  different  observers  favors  the  latter  view  and,  hence,  it 
must  be  concluded  that  the  union  between  the  antitoxin  and  the  toxin 
is  dependent  upon  the  presence  of  two  distinct  bodies  which  inter- 
act in  accordance  with  the  laws  of  valency.  The  chemical  nature  of 
this  process  is  betrayed  by  the  fact  that  concentrated  solutions  are 
more  effective  than  dilute,  and  that  it  is  accelerated  by  heat  and  re- 
tarded by  cold. 

In  accordance  w^ith  the  accepted  view  pertaining  to  chemical 
neutralization,  Ehrlich  assumed  that  the  molecule  of  the  toxin  con- 
sists of  two  separate  groups  or  atoms,  one  of  which  unites  with  the 
antitoxin  and  binds  it,  while  the  other  brings  its  specific  action  to 
bear  upon  the  latter.     The  intermediary  or  anchoring  portion  is  desig- 

1  Ann's  de  I'inst.  Pasteur,  1896. 

2  Giron.  della  R.  Acad,  di  Torino,  1898. 

*  Metchnikoff.  Ann's  de  I'inst.  Pasteur,  1898,  or  Landsteiner,  Centralbl.  fur 
Bakterienk.,  i,  1899,  25. 


THE  BLOOD  AND  LYMPH  AS  PHOTECTIVE  MECHANISMS        249 

nated  as  "haptophoro"  and  the  poisonous  •portion  as  "toxophorc." 
A  similar  view  has  been  expressed  by  Arrhenius  and  Madsen,^  who 
beUeve  that  tiie  toxin  possesses  a  weak  chemical  avidil}'  for  the  anti- 
toxin, the  resulting  reaction  being  similar  to  that  occurring  between 
a  weak  acid  and  base.  The  medium,  therefore,  would  embrace  un- 
combined  toxin  and  antitoxin  as  well  as  the  neutral  product.  It  is 
quite  impossible,  however,  to  explain  the  phenomena  of  hnmunity 
in  this  simjile  manner.  It  has  also  been  pointed  out  l)y  Craw  that  the 
neutralization  of  the  toxin  is  comparable  to  the  action  which  takes 
place  between  absorbing  membranes  and  certain  dyestuffs.  For 
example,  if  a  piece  of  filter  paper  is  placed  in  a  solution  of  fuchsin, 
some  of  the  d3^e  adheres  to  the  paper,  the  adhesion  increasing  with  the 
concentration  of  the  solution.  Furthermore,  if  the  piece  of  filter 
paper  is  first  divided  into  several  smaller  ones  which  are  then  placed 
in  the  solution  separately,  the  absorption  will  be  more  intense  than  that 
obtained  with  the  help  of  the  whole  paper.  It  is  also  conceivable  that 
the  union  of  the  antitoxin  and  toxin  is  not  exclusively  a  chemical 
process,  but  is  in  part  governed  by  physical  laws. 

An  explanation  regarding  the  relationship  existing  between  the 
toxins  and  the  cellular  components  of  the  body,  was  first  made  possi- 
ble upon  the  ])asis  of  Ehrlich's  theory  pertaining  to  the  nature  of  the 
protoplasmic  molecule,  published  in  1885.  When  applied  to  the  inter- 
action between  the  antitoxin  and  the  toxin,  it  is  generally  designated 
as  the  side-chain  theory ^  It  is  assumed  that  each  protoplasmic  mole- 
cule possesses  a  central  core  of  protein  upon  which  the  specific  activities 
of  the  cell  depend.  Branching  out  from  this  core  we  have  a  number 
of  side-chains,  or  "receptors,"  by  means  of  which  the  cell  is  brought 
into  relation  with  the  substances  contained  in  the  blood.  An  inter- 
change of  materials  is  effected  through  them  which  purposes  the 
substitution  of  the  waste  products  by  newly  acquired  nutritive  particles. 

This  process  may  be  illustrated  by  the  configuration  given  to  the 
free  and  combined  salicylic  acid  group.  In  this  case,  the  benzol  ring 
represents  the  radicle,  and  the  COOH  and  OH  the  side-chains  as 
follows : 

OH 

C 

/\ 
H— C       C— COOH 

H— C       C— H 

\/ 
C 

H 

»  Zeitschr.  fiir  physik.  Chem.,  1902. 

"^  Ehrlich,  Collected  Studies  on  Immunity,  translated  by  Bolduan,  New  York, 
1906. 


250  RESISTANCE    AND    IMMUNITY 

In  methyl  salicylate,  for  example,  the  configuration  is  changed  in  this 
way: 

OH 


CO2CH3 


In  a  corresponding  manner,  it  has  been  suggested  by  Ehrlich  that 
the  toxins  are  capable  of  exerting  their  destructive  action  upon  the 
body  by  becoming  chemically  bound  to  the  cells  through  the  inter- 
vention of  the  receptors  of  the  latter.  These  are  specific  in  their 
action  and  cease  their  function  as  soon  as  they  have  combined  with 
the  toxic  substance.  They  are  eventually  broken  down  and  de- 
stroyed. Thus,  when  the  haptophore  group  of  the  toxin  has  been 
anchored  to  a  receptoric  side-chain,  this  particular  feeler  of  the  cell 
is  of  no  further  use  and  is  cast  off.  The  formation  of  the  antitoxic 
substance  depends  upon  the  physiological  reaction  of  the  cell  to  this 
injury.  In  all  probability  the  latter  will  endeavor  to  compensate 
for  the  loss  of  its  receptors  by  the  formation  of  new  ones;  indeed,  the 
constant  stimulation  by  the  toxin  will  finally  lead  to  an  over-produc- 
tion of  receptoric  substance  which,  after  its  disconnection  from  the 
cell,  is  transformed  into  free  circulating  antitoxic  substances.  The 
latter  represent  the  so-called  antibodies  which  exert  their  protective 
action  even  in  regions  of  the  body  far  removed  from  their  place  of 
origin. 

The  side-chain  theory  of  Ehrlich,  therefore,  furnishes  a  means  for 
explaining  the  union  between  the  cells  of  the  animal  and  the  toxins,  as 
well  as  the  formation  of  the  antibodies.  In  the  form  just  given  it 
fails,  however,  to  account  for  several  phenomena  frequently  observed 
during  experiments  on  immunity;  for  example,  it  has  been  noted  that 
certain  pathogenic  bacteria  against  which  the  body  is  resistant,  do  not 
stimulate  the  formation  of  antibodies.  Moreover,  it  has  been  ascer- 
tained a  long  time  ago  that  the  normal  function  of  blood-serum  to 
destroy  certain  pathogenic  bacteria,  may  be  wholly  removed  by  sub- 
jecting it  to  a  temperature  of  56°  C,  but  a  serum  which  has  been 
rendered  inactive  in  this  way,  may  be  reactivated  by  the  addition  of 
a  small  quantity  of  normal  serum. 

These  and  other  facts  have  led  to  the  assumption  that  the  immune 
substances  appear  in  the  form  of  two,  namely,  as  a  thermolabile  body, 
known  as  "alexin,"  and  as  a  more  stable  body,  called  "sensitizing 
substance."  Thus,  it  is  believed  that  the  bacteriolytic  action  of  serum 
depends  upon  the  combined  action  of  these  two  substances.  The 
first  plays  the  part  of  the  principal  agent,  and  the  second,  that  of  the 
binder  which  renders  the  bacteria  vulnerable.     In  the  terminology 


THE  BLOOD  AND  LYMPH  AS  PROTECTIVE  MECHANISMS        251 


of  Ehrlich,  the  alexin  is  known  as  "complement,"  and  the  sensitizing 
substance  as  "  immune  body. "  It  is  held  by  this  investigator  that  the 
complement  cannot  enter  into  combination  with  the  foreign  substance, 
or  antigen,  unless  it  is  attached  to  it  by  a  mediator,  the  immune  body. 
In  accordance  with  an  earlier  suggestion  pertaining  to  the  construction 
of  the  toxin  molecule,  it  is  assumed  further  that  the  molecule  of  the 
immune  body  is  composed  of  two  groups  or  haptophores.  In  accord- 
ance with  their  degree  of  afhmty  for  either  the  antigen  or  the  comple- 
ment, one  of  these  groups  is  designated  as  "cytophile"  and  the  other 
as  "complementophile. "  On  account  of  its  "polarity,"  the  immune 
body  has  been  designated  as  the  "amboceptor." 

To  summarize:  the  antigen  (bacterium,  blood  cell,  poison,  etc.) 
cannot  be  affected  by  the  complement  (alexin  or  antibodies)  unless  it 
is  prepared  for  this  union  by  the  amboceptor  (immune  body  or  sensi- 
tizer) which,  on  account  of  its  polar- 
ity, is  capable  of  becoming  firmly 
anchored  to  it  as  well  as  to  the  com- 
plement. Thus,  the  interaction  be- 
tween the  complement  and  the  anti- 
gen is  made  possible  only  through 
the  intervention  of  the  amboceptor. 

Anaphylaxis. — The  term  anaphy- 
laxis (ana :  against,  phylaxis :  protec- 
tion) was  first  employed  by  Richet^ 
in   1905    to    indicate    an    increased 

sensitiveness  or  susceptibility  toward  infective  and  other  toxic  ma- 
terials. While  studjTJig  the  action  of  the  poison  derived  from  the  sea 
anemone,  he  found  that  if  a  small  dose  of  it,  which  produced  no 
symptoms  upon  its  first  injection,  was  followed  a  week  or  two  later 
by  another  small  dose,  the  animal  became  ill  and  usually  died.  Thus, 
the  most  acute  symptoms  may  follow  a  dosage  which  in  normal  animals 
produces  no  effects  at  all.  Inasmuch  as  a  summation  effect  cannot 
be  held  responsible  for  this  phenomenon,  because  the  interval  of  time 
between  the  two  successive  injections  is  altogether  too  long,  it  must 
be  concluded  that  this  condition  of  very  pronounced  susceptibility 
is  developed  at  some  time  in  the  course  of  this  reaction.  This  deduction 
implies  that  certain  bodies  are  called  into  existence  which  eventually 
produce  an  acute  toxic  state.  These  bodies,  however,  exhibit  a 
marked  specificity,  and  may  be  passively  transferred  to  otRer  animals. 
It  has  been  shown  in  guinea-pigs  that  they  may  be  transmitted  by  the 
female  to  her  offspring. 

This  susceptibility  was  recognized  in  reahty  before  Richet  applied 
to  it  the  name  of  anaphylaxis.  Thus,  it  had  been  observed  that  the 
administration  of  antitoxins  is  followed  at  times  by  most  severe 
symptoms,  giving  rise  to  what  Pirquet  and  Shick^  have  called  serum 

1  Soc.  Biol.,  Ixiv,  1908,  847,  and  Ann.  Inst.  Pasteur,  xxi,  1907. 

2  Wiener  klin.  Wochenschr.,  1902,  No.  26. 


A  •'  f\ns  C 

Fig.  122. — DiAGRAii  Illustrating 
Interactiox  Between  Complement  C 
AND  Antigen  A. 

Am,  amboceptor;  Cy,  cytophile 
and  Co,  complementophile  part  of 
amboceptor. 


252  RESISTANCE    AND    IMMUNITY 

sickness.  Arthus/  moreover,  had  proved  that  a  second  injection  of 
horse  serum  into  rabbits  freciuently  causes  a  verj^  intense  reaction,  so 
much  so  that  this  formerly  perfectly  harmless  procedure  becomes  dis- 
tinctly injurious.  Quite  similarly,  it  had  been  observed  that  a  tuber- 
culous person  is  hypersensitive  to  tubercuhn  and  that  injections  of 
cocain  eventually  give  rise  to  an  increased  susceptibility,  as  evinced 
by  undue  rises  in  the  body  temperature.^  A  similar  hypersensitiveness 
follows  the  repeated  administration  of  apomorphin.^  Anaphylaxis, 
therefore,  may  be  active  and  passive,  because  it  is  possible  to  render 
an  animal  anaphylactic  by  these  injections  and  also  to  transfer  this 
state  from  a  sensitized  to  a  normal  animal.  The  latter  process 
requires  the  injection  of  the  serum  of  an  anaphylactic  animal  which  is 
then  followed,  say  24  hours  later,  by  an  injection  of  the  antigen  origi- 
nally used  to  produce  this  condition  in  the  first  animal. 

Numerous  theories  have  been  advanced  to  explain  anaphylaxis. 
In  general  it  may  be  said  to  be  a  reaction  between  the  antigen  and  the 
specific  antibody.  In  the  same  way  as  antibodies  are  developed  after 
a  definite  period  of  incubation,  a  certain  antigen  may  eventually  give 
rise  to  anaphylactic  bodies,  such  as  toxogenin  (Richet)  anaph3dactin 
or  sensibilin.  This  complex  formed  by  the  antigen  and  antibody  be- 
comes poisonous  in  the  course  of  this  reaction,  but  it  may  also  be  true 
that  the  reaction  affects  the  medium  (blood-serum)  in  such  a  way 
that  it  assumes  toxic  properties. 

iSoc.  biolog.,  Iv,  1903,  817. 

2  Adnico,  Arch.  ital.  de  biol.,  xx,  1894. 

3  Richet,  Soc.  biolog.,  Iviii,  1905,  955. 


PART  III 
THE  CIRCULATION  OF  THE  BLOOD 

SECTION  VII 
THE  MECHANICS  OF  THE  HEART 


CHAPTER  XXIII 
A  COMPARATIVE  STUDY  OF  THE  CIRCULATORY  SYSTEM 

General  Arrangement  of  the  Vascular  System. — In  its  simplest 
form  the  circulatory  system  consists  of  two  parts,  namely,  a  fluid 
and  a  circular  tube,  the  cahber  of  which  is  greatly  increased  at  one 
point  to  represent  the  pumping  mechanism,  or  heart.  The  latter 
first  appears  in  the  form  of  a  smiple  bulbular  enlargement  of  the  gen- 
eral vascular  channel  and  finds  its  origin  in  the  deposition  of  large 
numbers  of  muscle  cells  possessing  automatic  properties.  This  enables 
the  walls  of  this  organ  to  contract  at  intervals  and  to  place  the  fluid 
within  under  a  higher  pressure  than  that  prevailing  in  the  tubes  with- 
out. In  consequence  of  this  difference  in  pressure,  the  fluid  is  forced 
through  orifices  (A)  and  (B)  into  the  distal  channel  (C),  but  as  every 
phase  of  contraction  of  the  musculature  must  necessarily  be  followed 
by  a  phase  of  relaxation,  the  fall  in  pressure  then  resulting  within  the 
heart  must  permit  the  fluid  to  return  into  the  central  cavity  (H). 

A  simple  arrangement  of  this  kind,  however,  is  not  adapted  for 
anything  dynamically  more  perfect  than  an  oscillatory  to  and  fro 
motion  of  the  fluid.  A  true  circular  motion  can  only  be  imparted  to 
the  fluid  within  this  system  by  guarding  the  aforesaid  orifices  {A  and 
B)  of  the  heart  (H)  by  valves  which  open  only  in  the  direction  of  the 
flow.  These  valves  having  been  put  in  their  proper  places,  the  con- 
traction of  the  cardiac  musculature  now  forces  the  fluid  across  the 
yielding  valve  flap  (A)  into  the  distal  channel  (C),  but  is  unable  to  drive 
it  through  the  opposite  orifice  (B),  because  this  valve  closes  immediately 
upon  the  first  increase  in  the  central  pressure.  A  moment  thereafter, 
however,  when  the  relaxation  of  the  cardiac  musculature  has  led  to 
the  establishment  of  a  lower  central  pressure,  the  valve  at  (B)  is  opened, 
allowing  the  fluid  to  reenter  the  central  compartment.     Inasmuch 

253 


254 


THE    MECHANICS    OF   THE    HEART 


as  valve  (A)  is  firmly  closed  at  this  time,  a  definite  direction  of 
flow  is  now  imparted  to  the  fluid.  It  leaves  the  heart  (H)  through 
the  arterial  orifice  {A)  and  cannot  return  to  this  organ  until  it  has 
traversed  the  entire  tube  (C) . 

The  channel  which  conveys  the  blood  away  from  the  heart  is 
known  as  an  artery,  while  the  one  returning  the  blood  to  this  organ  is 
called  a  vein.^  In  a  true  circulatory  system  these  two  divisions  are 
joined  by  a  multitude  of  fine  tubules,  designated  as  capillaries,  so  that 

the  entire  vascular  system  is  really  com- 
posed of  three  parts,  namely  of  arteries, 
capillaries,  and  veins.  In  accordance  with 
certain  structural  pecuHarities,  these  chan- 
nels may  be  subdivided  further  so  that  in 
final  analysis  the  circulatory  system  con- 
sists of  arteries,  arterioles,  arterial  capil- 
laries, capillaries  proper,  venous  capillaries, 
venules,  and  veins.  The  central  arterial 
tube  is  commonly  spoken  of  as  the  aorta, 
and  the  central  collecting  channel  as  the 
vena  cava. 

The .  Circulatory  System  in  the  Lower 
Animals. — In  the  lowest  forms  the  nutri- 
tion of  the  outlying  colonies  of  cells  is 
effected  by  progressive  and  oscillatory 
streams  which  are  brought  into  existence 
by  differences  in  pressure  as  well  as  by 
the  processes  of  diffusion  and  osmosis.  In 
the  highest  animals,  on  the  other  hand, 
these  simple  movements  give  way  eventu- 
ally to  a  complex  roundabout  motion  of 
the  body  fluid,  but  this  end  is  not  attained 
until  the  circulatory  mechanism  has  passed 
through  several  intermediary  stages  of  de- 
velopment. In  order  to  be  able  to  follow  these  changes  more  closely, 
it  seems  advisable  to  initiate  this  discussion  with  a  study  of  the  con- 
ditions existing  in  such  forms  as  the  sponges  which  may  be  said  to 
possess  a  circulation  of  the  most  elementary  kind.  We  find  here 
that  the  water  enters  through  numerous  pores  of  the  derma  and  is 
then  returned  to  the  surrounding  medium  by  way  of  the  central  canal 
and  the  osculum.  The  power  necessary  to  produce  this  fiow  is  fur- 
nished by  the  ciHa  with  which  the  aforesaid  passage  is  beset.  The 
higher  coelenterates  are  in  possession  of  an  alimentary  canal,  the 
smaller  recesses  of  which  extend  far  into  the  substance  of  their 
bodies.     In  this  way,  these  saccular  extensions  are  enabled  to  serve 

^  For  this  reason,  the  pulmonary  artery  is  known  as  an  artery,  although  it 
contains  venous  blood,  and  the  pulmonary  vein  as  a  vein,  in  spite  of  the  fact  that 
it  contains  freshly  aerated  blood. 


Fig.  123. — Schema  of  Simple 
Circulatory  System.  • 
/,  phase  of  contraction;  II, 
phase  of  relaxation  of  heart;  A 
and  B,  valves  guarding  cardiac 
orifices;  D,  arteries;  C,  capil- 
laries; E,  veins. 


A  COMPARATIVE  STUDY  OF  THE  CIRCULATORY  SYSTEM       255 


as  intermediary  agents  between  the  distant  cells  and  the  nutritive 
material  in  the  alimentary  passage.  In  the  medusa  well-marked 
gastrovaseular  streams  may  be  observed.  The  lower  vermes  ex- 
hibit an  arrangement  very  similar  to  that  found  in  the  eoelenterates. 
In  the  slightl}'  higher  forms,  however,  the  alimentary  tract  is  com- 
pletely separated  from  the  general  body  cavity,  so  that  the  gas- 
tric prolongations  are  enabled  to  assume  the  function  of  true  cir- 
culatory channels.  The  fluid  within  them  is  albuminous  in  character, 
and  is  moved  from  place  to  place  by  differences  in  pressure  produced 
by  the  general  movements  of  the  body.  In  some  annelids,  the  cir- 
culatory system  is  fully  differentiated  and  consists  of  a  dorsal  and  a 
ventral  tube  which  are  connected  with  one  another 
by  several  branches.  As  the  latter,  as  well  as  the 
adjoining  segments  of  the  dorsal  tube,  are  auto- 
matically active,  these  forms  may  be  said  to  be  in 
possession  of  a  real  heart  which,  however,  presents 
a  most  rudimentary  structure.  Its  most  essential 
characteristic  is  its  tubular  shape.  In  Arenicola, 
the  main  cardiac  cavity  is  constricted  at  one  point 
so  that  the  cardiac  tube  as  a  whole  appears  as  two 
distinct  compartments. 

Similar  differences  are  to  be  noted  among  the 
vertebrates.  Amphioxus,  for  example,  does  not 
possess  a  distinct  heart,  a  portion  of  its  posterior 
aorta  being  equipped  with  automatic  power.  It 
should  be  remembered,  however,  that  this  animal 
presents  the  first  indications  of  a  portal  circuit,  be- 
cause the  dorsal  aorta  gives  off  certain  branches  to 
the  intestine,  from  which  organ  the  blood  is  then 
collected  by  a  single  tube,  which  is  known  as  the 
portal  vein.  Having  traversed  the  capillaries  of 
the  liver,  the  blood  is  eventually  returned  into  the 
ventral  aorta. 

In  the  lower  animals,  the  power  of  rhythmic  activity  extends  over 
relatively  long  segments  of  the  dorsal  and  lateral  blood-vessels;  but 
in  the  fishes  the  heart  loses  its  diffuse  tubular  character,  and  the  power 
of  contraction  becomes  restricted  to  a  particular  area  of  the  vascular 
system.  These  animals  are  in  possession  of  a  cardiac  mechanism  which 
occupies  the  ventral  extent  of  the  body-cavity  and  presents  a  structure 
very  similar  to  that  found  in  the  higher  animals.  It  is  protected  on 
all  sides  by  a  membrane  which  is  reflected  from  its  base  to  form  a  pouch, 
the  so-called  pericardial  sac.  The  organ,  as  a  whole,  is  composed  of 
two  compartments,  an  antechamber  or  auricle,  and  a  main  chamber 
or  ventricle.  Moreover,  as  the  veins  do  not  unite  with  the  auricle  as 
separate  tubes,  but  become  confluent,  a  vestibular  chamber  is  formed 
which  is  commonly  designated  as  the  sinus  venosus.  Quite  similarly, 
the  aorta  does  not  arise  from  the  ventricle  itself,  but  from  an  appendage. 


Fig  124.— Dia- 
gram TO  Show  the 
Course  of  the  Blood 
Through  the  Fish 
Heart. 

SV,  sinus  venosus; 
A,  auricle;  V,  ven- 
tricle; BA,  bulbus  ar- 
teriosus; A,  aorta 
with  (C)  arteries  to 
gill  plates. 


256 


THE    MECHANICS    OF    THE    HEART 


known  as  the  conus  arteriosus.  All  these  different  parts  of  the  heart 
possess  contractile  powere,  their  action  being  coordinated  in  such  a 
manner  that  the  sinus  contracts  first,  the  auricle  next  and  the  ventricle 
and  conus  last  of  all.  The  blood  traverses  the  chambers  of  the  heart 
in  the  same  direction.  An  oscillator}'-  flow  is  made  impossible  by :  (a) 
the  proper  sequence  of  contraction  of  the  different  segments  of  the 
heart  and  (6)  the  fact  that  the  cardiac  orifices  are  guarded  by  valves 
which  open  onh'  in  the  direction  from  sinus  to  ventricle. 

In  accordance  with  the  force  which  the  different  parts  of  the  heart 
must  develop  in  order  to  propel  the  blood,  the  ventricle  contains  a 


^^ 


much  greater  amount  of  muscle  tissue  than 
the  auricle  or  sinus.  It  must  be  remem- 
bered that  the  ventricle  produces  the  pres- 
sure which  is  necessary  to  drive  the  blood 
through  the  entire  vascular  system.  In  ac- 
complishing this  end  it  must  overcome  the 
relative!}'  high  resistance  prevaihng  in  the 
peripheral  blood-vessels.  The  sinus  and 
auricle,  on  the  other  hand,  pump  the  blood 
merely  into  the  adjoining  ventricle  and,  as 
this  transfer  is  effected  at  a  time  when  the 
latter  is  in  a  condition  of  rest,  the  ante- 
chambers need  not  develop  anything  more 
than  ver}'  moderate  degrees  of  pressure. 

A  pecuhar  modification  of  the  circula- 
tory sj'stem  is  found  in  fish.  Inasmuch 
as  the  respiratory  interchange  in  these 
animals  is  effected  by  means  of  the  gills, 
this  particular  circuit  is  most  highly  de- 
veloped, while  the  lungs  with  their  pulmo- 
nary system  of  blood-vessels  are,  of  course, 
absent.  The  circulation  of  the  gills  is 
made  possible  by  a  number  of  afferent 
branches  which  are  given  off  from  the  ven- 
tral aorta  and  lead  to  the  different  gill- 
plates.  From  here  the  blood  is  conveyed 
to  the  dorsal  aorta  by  way  of  the  efferent  vessels.  In  this  way,  only  a 
part  of  the  blood  discharged  by  the  heart  finds  its  way  into  the  gills, 
where  it  is  aerated  and  is  distributed  subsequently  to  all  parts  of  the 
body.  It  is  returned  to  the  heart  thoroughly  charged  with  carbon 
dioxid.  The  fourth  subclass  of  the  fishes,  the  Dipnoi,  present  rather 
complicated  conditions,  because  they  are  equipped  \\'ith  lungs  as 
well  as  with  giUs  and  hence,  are  in  possession  of  a  pulmonary  and  a 
gill-circuit. 

The  heart  of  the  amphibians  is  situated  in  the  fore  part  of  the  body 
ventrally  to  the  first  vertebrae,  and  consists  of  a  sinus  venosus,  two 
auricles,  and  a  ventricle  with  its  bulbus  arteriosus.     The  blood  which 


Fig.  125. — Diagram  to  Show 

THE      COUESE      OF      THE      BlOOD 

Thbovgh  the  AiiPHiBiAX  Heaet. 
SV,  sinus  venosus;  RA, 
right  auricle;  LA,  left  auricle; 
T',  ventricle;  BA,  bulbus  arte- 
riosus; A,  aorta;  PA,  pulmo- 
nary arteries;  PV,  pulmonary 
veins.  The  striated  portion 
contains  venous  blood,  the 
dotted  portion  mixed  blood, 
and  the  clear  space,  arterial 
blood. 


A  COMPARATIVE  STUDY  OF  THE  CIRCULATORY  SYSTEM        257 


is  returned  from  the  system,  flows  into  the  right  auricle,  while  the 
blood  which  has  just  been  aerated  in  the  lungs,  enters  the  left  auricle. 
When  these  parts  contract,  both  types  of  blood  are  simultaneously 
forced  into  the  ventricular  cavity,  where  they  must  intermingle 
somewhat,  because  they  are  not  kept  apart  by  partitions.  It  must  be 
emphasized,  however,  that  a  thorough  mixture  of  the  aerated  with  the 
venous  blood  cannot  take  place,  because  the  interval  between  the 
auricular  and  ventricular  contractions  is  extremely  brief,  and  because 
the  ventricular  wall  contains  numerous  recesses,  in  which  at  least  a 
part  of  the  venous  and  oxygenated  types  of  blood  finds  separate  lodg- 
ment. It  is  only  natural  to  suppose  that  these  types  of  blood  will  be 
forced  into  those  parts  of  the  ventricle 
which  lie  directly  below  their  respective 
auricular  orifices.  It  is  also  true  that 
the  venous  blood  reaches  the  conus 
arteriosus  ahead  of  the  oxygenated,  be- 
cause the  right  expanse  of  the  ventricular 
cavity  lies  nearest  this  structure.  More- 
over, as  the  resistance  in  the  pulmonary 
circuit  is  less  than  that  in  the  systemic 
blood-vessels,  the  first  gush  of  ventricular 
blood,  venous  in  character,  must  find  its 
way  into  the  lungs  by  way  of  the  pulmo- 
nary artery,  while  the  aerated  portion 
following  it  must  necessarily  be  diverted 
into  the  peripheral  channels.  A  special 
system  of  blood-vessels  for  the  muscula- 
ture of  the  heart  is  not  present  in  amphi- 
bians. These  animals,  however,  are  in 
possession  of  a  hepatic  portal  system  and 
a  peculiar  renal  portal  system.  The 
latter  modification  of  the  vascular  mechan- 
ism finds  its  origin  in  the  double  blood- 
supply  of  the  amphibian  kidney.    It  will  be 


Fig.  126. — Diagram  to  Show 
THE  Course  of  the  Blood 
Through  the  REPTiLiA>f  Heart. 


SV,  sinus  venosus;  RA,  right 
auricle;  LA,  left  auricle;  V,  ven- 
tricle incompletely  divided  by  a 
septum;    A,    aorta;   PA,    pulmo- 

remembered  that  its  glomeruh  receive  their  "^^r^    ^J^J.^"*'!=.  f  ^'    p^!"^^"^^ 

^  .  .  vein,      ine  striated  portion  con- 

blood  from  the  aorta  directly,  while  the  re-  tains    venous    blood,   the  non- 
maining  portions  of  the  urinary  tubules  striated  arterial  blood. 
are  supplied  by  the  renal  portal  vein. 

The  heart  of  the  reptiles  resembles  that  of  the  amphibians  in 
several  particulars.  It  also  consists  of  a  sinus,  two  auricles,  and  a 
ventricle.  A  two-lipped  valve  is  situated  in  the  sino-auricular  orifice 
and  a  right  and  left  semilunar  valve  in  the  corresponding  auriculo- 
ventricular  openings.  The  ventricle,  from  which  the  aorta  and  pul- 
monary artery  emerge  separately,  is  divided  into  two  compartments 
by  a  muscular  septum.  The  separation  is  complete  in  the  crocodiles, 
but  incomplete  in  the  snakes,  lizards,  and  turtles.  In  the  animals 
named  last,  the  tendency  is  to  keep  the  venous  blood  separated  from 


258 


THE    MECHANICS    OF    THE    HEART 


the  aerated,  the  former  being  held  in  the  compartment  to  the  right, 
and  the  latter  largely  in  the  space  to  the  left  of  this  septum.  During 
the  contraction  of  the  ventricle,  the  edges  of  the  septal  flaps  are  brought 
together  so  that  the  largest  amount  of  the  venous  blood  is  forced  into 
the  pulmonary  artery,  while  the  oxygenated  blood  is  diverted  chiefly 
into  the  aorta.  But  while  definite  provision  has  been  made  in  these 
animals  to  prevent  a  complete  mixture  of  the  venous  with  the  aerated 
blood,  a  certain  degree  of  intermingling  is  still  possible  in  several  places 
outside  the  heart.  Excepting  certain  fish,  the  reptilian  heart  is  the 
first  to  exhibit  a  system  of  blood-vessels  for  the  nutrition  of  the  cardiac 

musculature.  The  hepatic  portal  is 
associated  with  a  renal  portal  system. 
The  heart  of  birds  possesses  four 
chambers,  namely  two  auricles  and  two 
ventricles.  A  distinct  vestibular  por- 
tion is  not  present.  The  blood  is  re- 
turned from  the  tissues  by  the  right 
and  left  post,  cavse.  It  enters  the  right 
auricle  and  then  the  right  ventricle, 
whence  it  is  conveyed  to  the  lungs 
through  the  pulmonary  arteiy.  Four 
pulmonary  veins  conduct  it  from  here 
to  the  left  auricle  and  left  ventricle, 
whence  it  again  attains  the  peripheral 
tissues  by  way  of  the  aorta  and  its 
branches.  Thus,  for  the  first  time,  the 
aerated  blood  is  completely  separated 
from  the  venous  blood  by  a  longitudinal 
septum  which  divides  the  heart  into  a 
right  and  a  left  side.  Each  side  in 
turn  embraces  an  antechamber,  or 
auricle,  and  a  main  chamber,  or  ven- 
tricle. The  auriculoventricular  orifices 
are  guarded  by  membranous  valve 
flaps,  the  right  being  large  and  muscular.  The  aortic  and  pulmonary 
orifices  are  beset  with  three  cup-shaped  valve-flaps.  Owing  to  the 
functional  importance  of  the  wings  and  the  corresponding  massive- 
ness  of  the  pectoral  muscles,  the  arteries  supplying  these  parts  are  very 
large  in  caliber.  Moreover,  in  agreement  with  the  position  of  the  legs, 
the  femoral  blood-vessels  are  found  far  forward  in  the  body. 

The  Circulatory  System  in  Mammals. — In  mammals,  the  heart 
is  divided  into  a  right  and  left  half  and  each  half  in  turn  into  an  ante- 
chamber, or  auricle,  and  a  main  chamber,  or  ventricle.  The  blood 
which  is  returned  from  the  tissues,  enters  the  right  auricle  by  way  of 
the  superior  and  inferior  venae  cavse,  while  the  blood  from  the  lungs 
is  conducted  into  the  left  auricle  by  way  of  the  pulmonary  veins. 
Two  distributing  channels  leave  the  heart,  namely,  the  pulmonary 


Fig.  127. — Diagram  to  Show 
THE  Course  of  the  Blood  Through 
THE  Heart  of  Birds. 

PC,  post,  cavse;  724,  right  auricle; 
LA,  left  auricle;  RV,  right  ventricle; 
LV,  left  ventricle;  PA,  pulmonary 
artery;  PV,  pulmonary  vein;  A, 
aorta. 


A  COMPARATIVE  STUDY  OF  THE  CIRCULATORY  SYSTEM       259 


artery  and  the  aorta.     The  former  conveys  the;  blood  from  the  right 
ventricle  to  the  lungs,  and  the  latter  from 
the  left  ventricle  to  all  parts  of  the  body. 

If  the  multituile  of  blood-vessels  con- 
stituting the  different  divisions  of  the  cir- 
culatory system  are  taken  and  moulded 
into  single  channels,  a  system  of  tubes  is 
formed  such  as  is  represented  in  the  ad- 
joining schema  (Fig.  128).  In  studying 
this  diagram  more  closely,  we  find  that 
a  droplet  of  blood  leaving  the  left  ven- 
tricle first  enters  the  central  arterial 
trunk,  or  aorta,  whence  it  escapes  into 
either  the  blood-vessels  of  the  head  or 
those  of  the  trunk  and  lower  extremities. 
In  either  case,  it  must  first  traverse  the 
arteries,  then  the  arterioles  and  finally, 
the  capillaries.  Having  attained  the 
other  side  of  these  extremely  fine  tubules, 
it  enters  the  venules  and  then  the  veins 
to  be  eventually  conveyed  into  the  right 
auricle.  The  venous  trunks  in  the  vi- 
cinity of  the  heart  are  designated  as  the 
superior  and  inferior  cava  respectively. 

This  extensive  system  of  blood-vessels 
which  suppHes  all  the  tissues  of  the  body 
with  the  exception  of  the  lungs,  consti- 
tutes the  greater,  or  systemic  circuit.  It 
embraces  two  specialized  smaller  divi- 
sions, namely,  the  coronary  and  portal 
circuits.  The  former  arises  from  the 
root  of  the  aorta  as  the  coronary  artery 
and  ends  in  the  right  auricle  as  the 
coronary  vein  or  sinus.  The  coronary 
blood-vessels  have  to  do  solely  with  the 
nutrition  of  the  heart.  The  portal  cir- 
cuit begins  with  the  arteries  supplying 
the  so-called  portal  organs,  namely,  the 
spleen,  pancreas,  Hver,  stomach,  and  in- 
testine. Having  traversed  the  different 
capillary  networks  of  these  organs,  the 
blood  is  collected  by  a  singlfe  channel, 
known  as  the  portal  vein,  and  is  then 
conducted  to  the  Hver,  whence  the  he- 
patic veins  convey  it  into  the  inferior 
vena  cava.  The  portal  circuit,  therefore,  is  concerned  chiefly  with  the 
processes  of  digestion  and  absorption. 


Fig.   128. — Schema  of  the 
Circulation. 

A,  aorta;  Ar,  arteries;  Art, 
arterioles;  AC,  arterial  capillaries; 
C,  capillaries;  VC,  venous  capil- 
laries; Ven,  venules,  Ve,  veins; 
VCS,  vena  cava  superior;  VCJ, 
vena  cava  inferior;  RA,  right 
auricle;  RV,  right  ventricle;  LA, 
left  auricle;  LV,  left  ventricle;  1, 
tricuspid  valve;  2,  mitral  valve; 
3,  pulmonary  semil.  valve;  4,  aortic 
semil.  valve;  PA,  pulmonary- 
artery;  L,  lungs;  PV,  pulmonary 
veins;  PO,  portal  organs;  PF,  por- 
tal vein;  HA,  hepatic  artery;  Li, 
liver;  HV,  hepatic  vein. 


260  THE    MECH.^>.-ICS    OF   THE    HEART 

The  second  principal  division  of  the  circulator}-  sj-stem  is  formed 
by  the  Usser  or  pulmonary  circuit.  It  consists  of  the  puhnonar\'  artery 
and  its  branches  which  conduct  the  blood  from  the  right  ventricle  into 
the  capillaries  of  the  lungs,  and  of  the  pulmonan,-  veins  which  collect 
the  aerated  blood  and  return  it  into  the  left  auricle.  Thus,  while 
every  drop  of  blood  is  forced  to  traverse  the  greater  and  lesser  circuits 
successively,  the  course  which  it  ma}'  pursue  is  not  restricted  to  one 
and  the  same  channel,  because  it  may  pass  either  into  the  capillaries 
of  the  head  or  into  those  of  the  heart,  portal  organs  and  posterior  ex- 
tremities. In  other  words,  a  large  number  of  shorter  and  longer 
paths  are  open  to  it. 

In  perfect  agreement  with  the  circulation  in  the  lower  forms,  the 
blood  of  the  mammal  is  made  to  flow  in  the  direction  indicated, 
because  the  contraction  of  the  auricles  antecedes  that  of  the  ventricles 
b}-  a  definite  period  of  time,  and  because  the  circulatory  channel  is 
beset  with  valves  which  open  onh'  in  one  particular  direction.  As  far 
as  the  second  factor  is  concerned,  it  should  be  stated  at  this  time  that 
there  are  three  sets  of  valves  to  be  considered,  namety:  (a)  the  auriculo- 
ventricular  which  guard  the  openings  between  the  auricles  and  ven- 
tricles, (6)  the  semilunar  which  are  situated  in  the  orifices  of  the  aorta 
and  pulmonary  artery,  and  (c)  numerous  venous  valves  which  are 
placed  as  a  rule  at  the  points  of  confluency  of  small  and  large  veins. 
The  first  set  of  valves  comprises  the  tricuspid  and  mitral,  the  former 
being  placed  in  the  right  and  the  latter  in  the  left  orifice.  Both  open 
downward  into  the  cavities  of  the  ventricles.  The  second  set  con- 
sists of  the  pulmonary  and  aortic  semilunar  valves.  Their  flaps  yield 
outward,  i.e.,  in  a  direction  away  from  the  ventricles.  The  venous 
valves  open  only  toward  the  heart. 

The  Circulatory  System  During  Fetal  Life. — The  circulator}' 
system  of  the  adult  human  being  finds  its  origin  in  the  system  which  is 
present  during  the  last  months  of  intra-uterine  hfe.  The  complete 
separation  of  the  young  from  the  mother  effected  at  birth,  necessitates 
first  of  all  the  presence  of  a  heart  that  is  capable  of  developing  an 
adequate  driving  force,  and  secondly,  several  ver}'  definite  alterations 
in  the  distribution  of  certain  blood-vessels  which  insure  a  perfect  con- 
tinuity of  the  vascular  channels.  It  should  be  emphasized,  however, 
that  the  changes  effected  at  bii'th,  are  not  the  only  ones  to  which  the 
circulation  of  the  human  embr}'o  is  subject  to.  Thus,  it  has  been 
established  that  the  early  vitelline  system  which  is  fully  developed 
during  the  third  week,  is  modified  several  times  to  meet  new  conditions, 
and  its  shortcomings  are  soon  compensated  for  by  the  formation 
of  the  allantoic  vessels  which  are  speciahzed  further  into  the  placental 
circulation.  The  following  pecuharities  are  evident  during  the  last 
months  of  gestation.  The  blood  spaces  of  the  placenta  which  lie  in 
contact  with  the  enormously  enlarged  capillaries  of  the  uterus,  unite 
eventually  to  form  two  blood-vessels,  commonly  known  as  the 
umbilical  arter}'-  and  vein.     The  latter  conveys  the  blood  from  the 


A  COMPARATIVE  STUDY  OF  THE  CIRCULATORY  SYSTEM       261 


placenta  to  the  fetus.  Very  soon  after  it  enters  the  fetus  through  the 
unibihcal  perforation,  it  divides  into  two  channels,  one  of  which 
unites  directly  with  the  inferior  vena  cava,  and  the  other  with  the 
portal  vein  in  the  immediate  vicinity  of  the  liver.     The  portal  branch 


Fig.  129. — The  Fetal  Circulation. 
P,  placenta;  UV,  umbilical  vein  carries  oxygenated  blood  and  unites  with  the 
vena  cava  inferior  (JVC)  and  portal  vein  (PV).  This  blood  mixes  wdth  the  venous 
blood  and  enters  the  right  atrium,  (RA)  being  here  diverted  largely  through  the  fora- 
men ovale  into  the  left  auricle  (LA).  From  here  it  passes  into  the  left  ventricle  (LV), 
aorta  (.-l)  and  either  into  head  circuit  or  abdominal  aorta  (A A).  Here  it  may  be 
diverted  into  the  portal  organs  (PO)  or  continue  onward  into  the  common  iliac  (C'JA), 
external  iliac  (EJA)  or  hypogastric  arteries  (HA).  In  the  latter  case  the  blood  again 
reaches  the  placenta  by  way  of  the  umbilical  arteries  (['.4).  The  blood  from  the  head 
enters  the  superior  vena  cava  (SVC)  and  right  auricle  (RA),  where  it  is  diverted  into 
the  right  ventricle  (RV)  and  pulmonary  artery  (PA).  From  here  it  passes  chiefly 
through  the  ductus  arteriosus  (DA)  into  the  aorta.  A  small  portion  of  its  traverses 
the  lungs  proper  (L)  to  be  returned  to  the  left  auricle  (LA)  by  way  of  the  pulmonary 
vein  (PV).  The  striated  vessels  contain  venous  blood  and  the  dotted  vessels,  mixed 
blood. 

is  known  as  the  ductus  venosus.  Whichever  course  the  placental 
blood  selects,  it  eventually  reaches  the  right  auricle.  It  is  to  be  noted, 
however,  that  it  is  immediately  mixed  with  the  blood  of  the  inferior 


262  THE  MECHANICS  OF  THE  HEART 

cava  which  in  all  probability  is  fully  loaded  with  the  waste  products 
of  the  fetal  tissues. 

On  account  of  the  peculiar  position  of  the  orifice  of  the  inferior 
cava  and  the  presence  of  a  lip-like  membrane,  known  as  the  Eustachian 
valve,  the  blood  entering  the  right  auricle  is  immediately  directed 
through  an  opening  in  the  interauricular  septum  into  the  cavity  of  the 
left  auricle.  This  orifice  which  thus  grants  a  free  passage  to  a  portion 
of  the  venous  blood  into  the  arterial  side  of  the  heart,  is  called  the 
foramen  ovale.  Under  normal  conditions  this  defect  is  closed  very 
shortly  after  birth,  its  place  being  taken  by  a  tense  fibrous  membrane 
which  forever  thereafter  remains  sharply  differentiated  from  the 
much  thicker  muscular  portion  of  this  septum.  In  certain  infants, 
however,  it  does  not  become  patent  until  several  weeks  after  birth; 
in  fact,  in  some  it  never  becomes  completely  impervious.  The  venous 
blood  then  continues  to  intermingle  with  the  arterial  and  the  more  so, 
the  larger  the  size  of  the  opening  remaining.  In  indication  of  the 
poor  aeration  of  the  tissues  resulting  in  consequence  of  this  condition, 
the  skin  and  mucous  membranes  of  these  children  retain  a  bluish 
appearance. 

From  the  left  auricle,  the  blood  passes  into  the  left  ventricle  and 
from  here  into  the  aorta.  If  it  is  now  diverted  into  the  blood-vessels 
of  the  head,  it  eventually  reaches  the  right  auricle  by  way  of  the  supe- 
rior vena  cava.  PecuHarly  enough,  the  stream  from  this  blood-vessel 
is  directed  in  such  a  way  that  it  flows  directlj"  through  the  right 
auriculoventricular  opening  into  the  ventricle  of  the  same  side  without 
seriously  interfering  with  the  cross-current  through  the  foramen  ovale. 
The  puhnonary  artery  then  conducts  the  blood  into  the  lungs,  but  as 
these  organs  are  inactive  and  are  merely  a  slowly  growing  mass  of 
tissue,  they  do  not  require  much  blood.  For  this  reason,  by  far  the 
largest  quantity  of  the  blood  of  the  pulmonary  artery  is  not  distributed 
to  the  lungs  at  all,  but  escapes  into  the  aorta  b}^  way  of  a  special  chan- 
nel, commonly  called  the  ductus  arteriosus.  Onty  an  insignificant 
portion  of  the  blood  of  the  puhnonary  artery  actually  reaches  the  capil- 
laries of  the  lungs,  whence  it  again  attains  the  left  auricle  by  way  of 
the  puhnonary  veins.  This  blood,  of  course,  serves  solely  the  purpose 
of  supplying  nutritive  material  to  the  growing  lung  tissue. 

A  droplet  of  blood  may  pursue  the  course  just  outlined  a  nmnber  of 
times,  but  it  may  also  happen  that  it  is  forced  into  the  posterior  parts 
of  the  body,  i.e.,  into  the  portal  circuit  or  into  the  blood-vessels  of  the 
legs,  and  eventually  regain  the  heart  by  way  of  the  inferior  cava.  Last 
of  all,  it  may  leave  the  fetus  altogether  and  return  to  the  placenta  by 
way  of  the  hypogastric  branches  and  the  umbihcal  artery.  Clearly, 
therefore,  the  paths  which  a  drop  of  blood  may  follow,  are  even  more 
numerous  and  diverse  in  the  fetus  than  they  are  in  the  adult.  It  may 
be  said,  however,  that  a  verj'  considerable  portion  of  the  blood  allotted 
to  the  posterior  part  of  the  body,  constantly  leaves  the  fetal  channels 
to  be  replenished  in  the  placenta.     Considered  in  a  general  way,  it  is 


THE  ARRANGEMENT  OF  THE  MUSCULATURE  OF  THE  HEART   263 

obvious  that  tho  circulation  of  the  fetus  greatly  favors  the  head 
region,  the  proper  growth  of  the  nervous  system  being  of  much  greater 
importance  than  that  of  the  other  tissues  and  organs. 

The  distinctive  features  of  the  fetal  system  may,  therefore,  be 
said  to  be  the  ductus  venosus,  the  foramen  ovale,  the  ductus  arteriosus, 
the  hypogastric  arteries,  and  the  umbilical  arteiy  and  vein.  The 
obUteration  of  these  blood-vessels  is  initiated  immediately  after  birth, 
but  several  days  usually  elapse  before  this  process  has  been  completed. 
Thus,  the  distal  portions  of  the  hypogastric  arteries  are  usually  found 
to  be  impervious  at  the  end  of  the  third  or  fourth  day,  while  the 
obliteration  of  the  ductus  venosus  and  umbilical  vein  is  not  effected 
until  the  end  of  the  first  week  and  that  of  the  ductus  arteriosus  not 
until  the  end  of  the  third  or  fourth  week. 


CHAPTER  XXIV 

THE  ARRANGEMENT  OF  THE  MUSCULATURE  OF  THE  HEART 
THE  VALVES  OF  THE  HEART 

The  Structure  of  the  Auricles  and  Ventricles. — The  adult  human 
heart  measures  about  125  mm.  in  length,  87  mm.  in  breadth,  and  62 
mm.  in  thickness.  Its  volume  exhibits  the  following  variations: 
22  c.c.  at  birth,  155  c.c.  during  the  fifteenth,  250  c.c.  during  the 
twentieth,  and  280  c.c.  during  the  fiftieth  year.  Thus,  it  will  be  seen 
that  its  growth  is  most  rapid  during  early  life.  Beginning  with  about 
the  fifteenth  year,  the  heart  of  the  male  becomes  larger  than  that  of 
the  female.  At  birth  the  organ  weighs  about  24  grams,  at  puberty 
250  grams,  and  in  adult  life  310  grams.  The  heart  of  the  adult  female 
weighs  about  255  grams.  To  begin  with,  the  ventricles  are  equally 
heavy,  but  at  the  end  of  the  second  year  the  left  weighs  about  twice 
as  much  as  the  right,  this  relationship  of  2  :  1  being  retained  until 
death. 

The  wall  of  the  heart  is  composed  of  three  layers,  namely  a  lining 
membrane,  or  endocardium,  a  median  coat,  or  myocardium,  and  an  outer 
investment,  or  epicardium.  The  outermost  layer  forms  at  the  same 
time  the  inner  or  visceral  half  of  the  pericardium  which  is  then  reflected 
from  the  base  of  the  heart  to  serve  as  the  parietal  half  of  this  capsular 
investment.  The  space  which  is  thus  cut  off  from  the  general  cavity 
of  the  thorax,  is  known  as  the  pericardial  sac.  Its  opposing  surfaces 
are  moistened  with  a  few  drops  of  a  lymph-like  fluid,  called  the  peri- 
cardial fluid.  The  function  of  the  latter  is  to  lessen  the  friction  which 
must  necessarily  be  associated  with  the  changes  in  the  volume  of  the 
heart.     The  pericardium  contains  many  elastic  fibers  which  coalesce 


264  THE  MECHANICS  OF  THE  HEART 

with  the  adventitia  of  the  large  veins.  Elastic  fibers  and  a  few  smooth 
muscle  cells  are  also  scattered  through  the  endocardium,  and  espe- 
cially through  the  lining  of  the  auricles.  As  far  as  the  function  of  the 
pericardium  is  concerned,  it  may  be  stated  that  it  exerts  a  restraining 
influence  upon  the  musculature  of  the  heart,  insuring  a  certain  com- 
pactness of  its  substance,  and  serving  to  counteract  the  effects  of  un- 
usual degrees  of  pressure  within  its  chambers.  Thus,  any  defect  in 
this  enveloping  membrane  generally  permits  of  a  decided  outward 
bulging  of  the  cardiac  substance  which  in  turn  may  lead  to  an  in- 
competency of  the  valves. 

It  is  very  suggestive  that  the  heart  of  mammals  is  composed  of  a 
type  of  muscle  tissue  which  occupies  an  intermediate  position  between 
the  primitive  smooth  muscle  and  the  specialized  striated  muscle.  In 
fact,  its  high  content  in  sarcoplasm  would  tend  to  ally  it  more  closely 
with  the  former  tissue.  It  is  also  of  interest  to  note  that  in  the  lower 
forms  the  cardiac  muscle  is  composed  of  actual  cells  possessing  a  spindle- 
like shape  and  an  elongated  nucleus.  In  these  animals,  the  heart 
appears  essentially  as  a  simple  tubular  muscle,  the  different  parts  of 
which  are  intimately  connected  with  one  another  by  bridges  of  muscle 
tissue. 

In  the  mammals,  on  the  other  hand,  the  mass  of  the  ventricular 
musculature  is  completely  separated  from  the  auricles  by  a  heavy 
deposit  of  connective  tissue  situated  in  the  domain  of  the  auriculo- 
ventricular  groove.  It  is  to  be  noted  that  the  perimysium  enveloping 
the  muscle  fibers  increases  very  markedly  at  this  level  of  the  heart, 
while  the  muscle  fibers  decrease  in  number,  their  places  being  taken 
eventually  by  strong  fibrotendinous  rings,  the  so-called  annuli  fibrosi. 
These  structures  which  occupy  the  auriculoventricular  furrow, 
serve  as  the  framework  to  which  the  different  strands  of  muscle-tissue 
are  fastened.  But,  while  the  auricles  and  ventricles  of  the  mammalian 
heart  are  not  united  by  direct  bridges  of  muscle,  they  are  brought 
into  functional  relation  by  a  strand  of  musculonervous  tissue  which  is 
known  as  the  auriculoventricular  bundle  or  the  bundle  of  His. 

In  accordance  with  the  low  degree  of  pressure  developed  by  the 
auricles,  the  musculature  of  these  chambers  appears  as  a  thin  capsule 
to  which,  however,  a  seemingly  disproportionate  strength  is  given  by 
the  musculi  pectinati.  These  projecting  strands  of  muscle  tissue  are 
especially  numerous  in  the  domain  of  the  appendix  auriculae,  where 
they  encroach  upon  the  main  cavity  in  such  a  manner  that  saccular 
recesses  are  formed  which  are  known  as  the  foramina  Thebesii.  In 
this  way,  the  capacity  of  the  central  expanse  of  the  auricular  cavity, 
which  lies  directly  above  the  auriculoventricular  orifice,  may  be  greatly 
increased  at  any  time  without  incurring  the  danger  of  over-distending 
and  rupturing  its  wall.  A  circular  depression  upon  the  interauricular 
septum  indicates  the  location  of  the  foramen  ovale  of  intra-uterine  life. 
In  addition,  the  right  auricular  cavity  presents  the  orifice  of  the  coro- 
nary sinus,  guarded  by  the  delicate  valve  of  Thebesius.     In  the  left 


THE  ARRANGEMENT  OF  THE  MUSCULATURE  OF  THE  HEART   265 


cavity,  wo  observe  the  orifices  of  the  pulmonary  veins,  generally  four 
in  number. 

The  musculature  of  the  principal  mass  of  the  auricles  is  arranged 
as  an  outer  transverse  and  an  inner  longitudinal  layer.  ^  Moreover, 
while  each  auricle  really  constitutes  an  anatomical  and  functional 
entity,  a  number  of  fibers  of  the  superficial  coat  always  pass  from  one 
side  to  the  other,  thus  joining  the  two.  In  this  way,  a  coordinated 
activity  of  the  two  chambers  is  assured.  Circular  fibers  are  much 
in  evidence  at  the  orifices  of  the  larger  veins  and  at  the  coronary  sinus. 
It  should  be  emphasized,  however,  that  these  muscular  rings  do  not 
act  as  sphincters,  but  merely  tend  to  lessen  the  size  of  the  opening. 

A  more  comphcated  relationship  is  presented  by  the  musculature 
of  the  ventricles.  As  these  parts  are  called  upon  to  develop  the  force 
necessary  to  drive  the  blood  through  the 
distant  vascular  channels,  it  cannot  sur- 
prise us  to  find  that  their  walls  possess 
a  great  massiveness  and  strength.  Fur- 
thermore, as  the  left  ventricle  is  destined 
to  supply  the  blood-vessels  of  the  greater 
circuit  and  thus  to  perform  by  far  the 
greatest  amount  of  work,  it  may  be  as- 
sumed that  its  wall  is  much  thicker  and 
stronger  than  that  of  the  right  cavity. 
In  cross-section,  the  left  cavity  appears 
as  a  rounded  orifice  enveloped  by  a  heavy 
frame  of  muscle-tissue,  while  the  right 
compartment  presents  itself  as  a  cres- 
cent-shaped slit  limited  externally  as  by 
a  relatively  thin  layer  of  muscle  (Fig.  130) 
however,  that  the  basal  portion  of  the  right  cavity  gradually  assumes 
a  more  conical  outhne,  and  that  the  apex  of  the  heart  is  formed  ex- 
clusively by  the  left  ventricle.  Thus,  if  the  heart  is  divided  trans- 
versely beginning  at  its  apex,  the  left  ventricular  cavity  is  opened 
first  and  the  right  cavity  only  after  another  section  at  a  much  higher 
level  has  been  made. 

Although  the  ventricular  muscle  fibers  do  not  exhibit  definite 
points  of  origin  and  insertion,  it  is  permissible  to  assume  that  they 
begin  in  the  fibrous  tissue  at  the  auriculoventricular  junction; 
indeed,  the  entire  ventricular  network  may  be  likened  to  a  muscular 
basket  fastened  above  to  the  annuh  fibrosi.  Three  distinct  layers 
are  discernible,  namely,  an  outer,  a  middle,  and  an  inner.  The  fibers 
of  the  outer  and  inner  layers  are  arranged  longitudinally,  while  those 
of  the  median  coat  are  directed  transversely  to  the  long  axis  of  the 
heart  and  pass,  therefore,  circularly  around  the  lumen  of  the  ventricu- 
lar cavity.  Beginning  at  the  base  of  the  heart,  the  outer  fibers 
extend  spirally  toward  the  apex,  but  in  such  a  way  that  their  general 
1  Krehl,  Abhandl.  der  sachs.  Gesellsch.  der  Wissenschaften,  xvii,  1891,  346. 


Fig.  130. — Transverse  Sec- 
tion Through  Heart  of  Dog,  3 
CM.  Above  Apex  to  Show  Shape 
AND  Position  of  Ventricular 
Cavities. 

It  should  be  remembered. 


266  THE    MECHANICS    OF    THE    HEART 

direction  is  oblique.  Rather  numerous  on  the  left  side,  they  form 
merely  a  thin  superficial  layer  in  the  right  ventricle.  At  the  apex 
they  again  curve  upward  and  are  finally  inserted  in  the  septum  and 
adjoining  papillary  muscles.  The  inner  fibers  begin  in  the  apical 
whorl  and  extend  almost  in  a  straight  line  toward  the  base,  but  it  is 
not  quite  correct  to  look  upon  them  merely  as  continuations  of  the 
outer  fibers. 

MalP  divides  the  superficial  fibers  into  the  bulbospiral  and  sino- 
spiral.     The  former  begin  at  the  conus,  the  left  side  of  the  aorta  and 


FiQ.  131. — Schema,  to  Show  the  Course  of  the  Superficial  a^-d  Deep  Fibers  of  the 
Bulbospiral  and  Sdcospiral  Systems.  The  Heart  is  Viewed  From  the  Dorsal  Side. 
BS,  superficial  bulbospiral  system;  BS',  deep  bulbospiral  system;  .SS,  superficial 
spinospiral  system;  SS',  deep  sinospiral  system;  C,  circular  fibers  round  the  conus; 
C",  circular  fibers  round  the  base  of  the  aorta  and  the  left  ostium ;  LRV,  longitudinal 
bundle- of  right  ventricle,  from  membranous  septum  to  right  ventricle;  IV,  interven- 
tricular or  interpapillary  laj'er.      (Mall.) 

the  left  side  of  the  left  ostium  venosum  and  pursue  a  spiral  course  to 
the  apex,  where  they  enter  into  the  formation  of  the  posterior  horn 
of  the  vortex.  Some  of  these  fibers  end  in  the  septum  and  some  in 
the  posterior  wall  of  the  left  ventricle  where  they  terminate  in  the 
basal  portion  of  this  papillary  muscle.  The  fibers  of  the  sinospiral 
system  originate  from  the  posterior  aspect  of  the  heart  in  the  vicinity 
of  the  right  venous  ostium.  They  pursue  a  spiral  course  to  the  apex, 
where  they  form  the  anterior  horn  of  the  vortex  and  terminate  in  the 
anterior  wall  of  the  left  ventricle  and  corresponding  papillary  muscle. 
In  addition,  Mall  recognizes  a  deep  bulbospiral  and  sinospiral  system 
1  Am.  Jour,  of  Anatomy,  ii,  1911,  211. 


THE  ARRANGEMENT  OF  THE  MUSCULATURE  OF  THE  HEART   2G7 

of  fibers.  Both  are  directed  more  transversely  then  the  superficial 
layers.  The  former  encircle  the  left  cavity  and  the  latter  the  right 
cavity,  and  finally  surround  the  large  blood-vessels  at  the  base  of  the 
heart. 

These  two  longitudinal  layers,  form,  so  to  speak,  a  shng-like 
support  for  the  circular  fibers  which  are  especially  numerous  on  the 
left  side,  and  give  an  unusual  volume  and  strength  to  this  compart- 
ment. It  must  be  evident  that  the  circular  coat  is  the  most  important 
dynamic  factor,  because  its  constrictor  action  serves  to  lessen  the 
lumen  of  the  ventricular  cavity  in  a  most  decided  manner,  thus  giving 
rise  to  the  pressure  which  is  required  to  drive  the  blood  through  the 
system.  It  should  be  emphasized,  however,  that  although  each  ven- 
tricle is  constructed  in  such  a  way  that  it  forms  a  muscular  unit,  the 
joint  action  of  the  two  is  assured  by  certain  strands  of  fibers  which  pass 
from  side  to  side  and  envelop  both  compartments. 

On  contraction,  each  ventricular  mass  of  tissue  assumes  a  rounded 
outUne  so  that  the  two  compartments  become  sharply  differentiated 
from  one  another  by  a  groove  which  extends  obliquely  downward 
from  a  point  above  and  on  the  right  side  to  a  point  below  and  on  the 
left.  Moreover,  in  accordance  with  the  general  direction  of  the  fibers 
of  the  outer  coat,  the  entire  ventricular  mass  is  turned  at  this  time 
slightly  around  its  longitudinal  axis  so  that  the  apical  center  is  rotated 
from  left  to  right  and  forward.  For  this  reason,  a  more  extensive 
area  of  the  left  side  of  the  heart  is  brought  into  view  during  this  period ; 
and  naturally,  only  the  left  ventricle  then  presents  itself  below  the 
interventricular  groove,  because  the  apex  is  formed  solely  by  the  mus- 
culature belonging  to  this  compartment. 

The  Arrangement,  of  the  Valves. — With  the  exception  of  the  ap- 
pendix auriculae,  the  cavity  of  the  auricle  presents  a  perfectly  smooth 
internal  surface.  In  the  ventricles,  on  the  other  hand,  open  spaces 
are  encountered  solely  below  the  orifices  of  the  aorta  and  pulmonary 
artery.  The  former  is  designated  as  a  rule  as  the  aortic  vestibule 
and  the  latter  as  the  conus  arteriosus.  The  remaining  space  of  each 
ventricle  is  rendered  rugose  and  uneven  by  numerous  projecting  bundles 
of  muscle- tissue  which  appear  in  the  shape  of  (a)  columns  raised  in 
relief  from  the  wall,  (6)  as  isolated  cords  of  tissue  stretching  directly 
through  the  cavity,  and  (c)  as  free  conical  and  nipple-shaped  elevations 
projecting  for  a  short  distance  into  the  lumen  of  the  cavity.  The  first 
are  known  as  columnce  carnece.  Their  function  seems  to  coincide  with 
that  of  the  general  mass  of  the  cardiac  tissue.  The  second,  called 
moderator  bands,  are  found  most  frequently  in  the  right  cavity.  They 
arise  as  a  rule  from  the  interventricular  septum  and  are  inserted  in 
the  outer  wall.  Obviously,  their  purpose  is  to  prevent  an  excessive 
outward  movement  of  the  latter  and  an  undue  distention  of  the  cavity 
as  a  whole.  The  third,  commonly  referred  to  as  the  papillary  jnusdes, 
are  in  functional  relation  with  the  principal  mass  of  the  cardiac  mus- 
culature and  serve  as  points  of  attachment  for  the  chordce  tendinece, 


268  THE  MECHANICS  OF  THE  HEART 

which,  as  the  name  indicates,  are  tendinous  cords  extending  from 
here  to  the  overlying  valve  flaps. 

The  Auriculoventricular  Valves. — It  has  been  stated  above  that 
the  blood  flows  through  the  heart  in  a  perfectly  definite  direction, 
because  the  contraction  of  the  ventricles  does  not  take  place  until  the 
contraction  of  the  auricles  has  been  completed,  and  because  the  orifices 
connecting  the  different  chambers  of  this  organ  are  opened  and 
closed  in  perfect  harmony  with  the  activity  of  the  cardiac  muscle. 
There  are  really  two  ways  in  which  the  cardiac  orifices  could  be  closed : 
namely,  by  heavy  rings  of  muscle  tissue  which  by  their  sphincter-like 
action  obUterate  the  passage  in  the  manner  of  the  diaphragm  of  a 
photographic  camera,  or  by  membranous  flaps  wliich,  in  the  manner  of 
a  door,  swing  directly  across  the  openings.  Clearly,  the  closure  of  an 
orifice  by  a  layer  of  circular  musculature  is  an  action  which  requires 
power  and,  therefore,  necessitates  the  expenditure  of  a  considerable 
amount  of  energj'.  If  this  mechanism  were  actually  in  use  in  our 
heart,  it  would  mean  that  the  pressure  developed  by  this  organ  would 
have  to  be  apportioned  in  part  to  the  closure  of  its  orifices,  and  in  part 
to  the  blood  as  driving  force.  For  this  reason,  the  use  of  valves  must 
be  considered  as  a  much  more  economical  means,  inasmuch  as  it  does 
not  necessitate  a  division  of  the  cardiac  energy.  The  different  valve 
flaps  are  moved  into  place  passively  bj"  the  relative  degrees  of  pressure 
upon  their  two  surfaces,  and  hence,  all  the  power  developed  by  the 
heart  may  be  directed  to  the  single  purpose  of  propelling  the  blood. 
In  this  way,  the  closure  of  the  valves  is  accomplished,  so  to  speak, 
incidentally  in  the  course  of  the  general  muscular  contraction. 

The  auriculoventricular  openings  are  large  and  are  especially 
adapted  for  a  quick  transfer  of  blood.  The  left  is  oval  in  shape  and 
smaller  than  'the  right  which  possesses  a  rounded  triangular  outhne. 
Both  orifices  are  surrounded  by  fibrous  rings  which  are  connected 
with  the  mass  of  the  fibrocartilaginous  tissue  situated  at  the  auriculo- 
ventricular junction.  The  different  valve  flaps  are  composed  of  double 
folds  of  endocardium,  strengthened  by  fibrous  tissue  and  containing  a 
few  elastic  fibers  and  muscle  cells.  The  latter  are  arranged  radially 
and  are  connected  with  the  auricular  musculature.  The  basal  por- 
tions of  the  flaps  are  fastened  to  the  walls  of  the  orifice,  while  their 
tips  and  thin  margins  are  free  and  project  far  into  the  cavity. 

The  left  valve,  known  as  the  mitral,  is  composed  of  two  triangular 
flaps  of  unequal  size,  while  the  right,  or  tricuspid,  consists  of  three 
flaps.  Both  valves  3'ield  solely  in  a  downward  direction  and  on  closure 
assume  a  position  transversely  across  the  opening.  A  perfect  approxi- 
mation of  the  different  flaps  is  made  possible,  on  the  one  hand,  by  the 
muscle  tissue  forming  the  wall  of  the  orifice,  and,  on  the  other,  by  the 
chordae  tendineae  with  which  their  lower  surfaces  are  connected.  Ob- 
viously, the  contraction  of  the  former  gives  a  certain  firmness  to  the 
frame  in  which  the  valve  flaps  are  hung  so  that  their  basal  portions 
become  fixed,  while  their  tips  attain  a  wide  range  of  movement.     In 


THE  ARRANGEMENT  OF  THE  MUSCULATURE  OF  THE  HEART   2G9 

addition,  this  firmness  and  greater  prominence  of  the  wall  of  the  orifice 
must  tend  to  lesson  the  size  of  the  passage.  The  arrangement  of  the 
chordcE  tendinccB  nmst  seem  very  perplexing  to  the  casual  observer. 
On  closer  examination,  however,  it  will  be  seen  that  they  arise  from 
the  papillary  muscles  which  are  situated  at  some  distance  below  the 
basal  portions  of  the  different  valvd  flaps.  A  very  clear  picture  of 
the  course  pursued  by  them  may  be  obtained  in  the  left  ventricle,  in 
which  only  two  papillary  prominences  are  present.     In  the  right  cavity, 

on  the  other  hand,  the  condi- 
tions are  less  simple,  because  we 
find  here  three  papillary  projec- 
tions and,  in  addition,  also  a 
number  of  chordae  which  origi- 


iiG.   132.  Fig.   133. 

Fig.  132. — Heart  of  the  Cow,  With  Left  Auricle  and  Ventricle  Laid  Open. 
(Miiller.) 

a,  Root  of  the  aorta ;  b,  spaces  in  the  wall  of  the  auricle ;  c,  c,  orifices  of  the  pulmonary 
veins;  I,  I,  pulmonary  veins;  p,  p,  papillary  muscles;  q,  q,  columnae  carnesD.  A,  orifice 
of  the  aorta;  K,  left  ventricle;  S,  septum;  V,  left  auricle;  W,  lateral  wall  of  left  ventricle; 
1,   1,  2,  leaflets  of  mitral  valve. 

Fig.  133. — Schema  to  Show  Fan-like  Distribution  of  Chords  TENDiNEiE  (C)  from 
A  Single  Papillary  Muscle  (P),  Situated  Underneath  (F),  Two  Ad  joining  Valve 
Flaps. 


nate  from  the  septum  itself.  Very  soon  after  they  leave  their  places 
of  origin,  the  individual  chordae  divide  into  smaller  strings  which  ex- 
tend fan-like  through  the  cavity  to  be  inserted  eventually  upon  the 
free  margins  and  more  centrally  located  areas  of  the  flaps  above  them. 
Moreover,  as  the  papillary  muscles  are  placed  as  a  rule  almost  ver- 
tically below  the  points  of  union  between  two  neighboring  flaps,  each 
colony  of  chordas  concerns  itself  chiefly  with  the  two  margins  nearest 
to  them.  In  reaching  their  points  of  insertion  they  frequently  cross 
one  another,  but  without  impairing  their  movement. 

The  structure  and  general  arrangement  of  the  chordae  prove  very 


270  THE  MECHAXICS  OF  THE  HEART 

convincingh-  that  they  are  instrumental  in  approximating  the  different 
valve  flaps.  Thus,  by  permitting  the  different  flaps  to  be  moved  into 
a  position  transverseh'  across  the  orifices  and  no  farther,  they  serve 
a  pm-pose  ver^,-  suuilar  to  that  of  the  guy-ropes  of  a  sail.  Secondly,  as 
a  number  of  chordse  are  always  inserted  upon  the  central  area  or  body 
of  the  flaps,  they  prevent  the  bulging  or  bellying  of  the  entire  valve 
into  the  aui'icular  cavity,  Thirdl}',  as  the  papillarv'  projections  from 
which  the  chordse  arise  are  usuall}'  placed  vertically  below  the  space 
between  two  adjoining  flaps,  and  as  the  individual  strings  are  inserted 
upon  the  margins  of  both,  they  must  necessarily  exert  a  traction  toward 
a  common  center  which  is  situated  midway  below  the  planes  of  the  two 
flaps.  In  this  way  the  margins  of  the  diiferent  flaps  are  pulled  together 
transverseh'  and  are  then  held  firmly  in  place.  It  maj^  be  assumed 
that  the  papillaiy  muscles  take  part  in  the  general  contraction  of  the 
ventricles,  thereby  furnishing  a  more  soh'd  basis  for  the  chordae  to  act 
upon;  in  fact,  it  maj^  be  said  that  the  contraction  of  these  projections 
exerts  a  certain  traction  upon  them  wliich  facilitates  their  unfolding 
and  the  approximation  of  the  valve-flaps. 

The  auriculoventricular  valves  are  opened  ver>'  soon  after  the  ces- 
sation of  the  contraction  of  the  ventricles.  Gradually,  as  the  blood 
flows  into  the  auricles  from  the  central  veins,  the  intra-auricular  pres- 
sure is  raised  above  that  prevaiHng  in  the  now  passive  ventricles. 
In  consequence  of  the  higher  pressure  exerted  upon  their  upper  sur- 
faces, the  flaps  are  forced  sUghtly  apart  with  the  result  that  the  blood 
now  rushes  into  the  ventricular  cavity.  It  should  be  remembered, 
however,  that  the  flaps  are  not  moved  as  a  door  would  be  on  opening 
it,  because  their  basal  portions  are  attached  to  a  rather  rigid  cushion 
of  tissue  and  remain,  therefore,  relatively  fixed.  Their  tips,  on  the 
other  hand,  are  bent  sharply  downward  so  that  each  flap  assumes  the 
shape  of  a  crescent,  the  concavity  of  which  faces  the  ventricle. 

The  auricular  contraction  following  verk'  shorth'  after  the  initial 
opening  of  the  auriculoventricular  valve,  renders  the  orifice  between 
these  chambere  more  funnel-shaped.  The  blood  being  driven  directly 
into  the  narrowest  part  of  this  passage  opposite  the  tilted  tips  of  the 
flaps,  is  thus  directed  into  the  central  expanse  of  the  ventricles  without 
being  able  to  foiTn  secondaiy  currents  or  whorls  which  might  seriously 
impair  its  flow.  Quite  naturally,  when  this  column  of  blood  traverses 
the  ostium,  the  flaps  are  pushed  far  apart,  but  are  not  brought  into 
actual  contact  with  the  ventricular  wall.  The  space  between  them 
and  the  surface  of  the  latter  is  filled  with  blood.  This  is  of  great  dynam- 
ical importance,  because  if  the  flaps  were  forced  against  the  wall,  it 
would  be  difficult  to  dislodge  them  and  to  move  them  into  the  position 
of  closure.  Obviously,  the  latter  movement  can  only  be  effected  if 
their  under  surfaces  remain  exposed  to  the  ventricular  pressure. 

The  contraction  of  the  auricles  fills  the  ventricles  to  their  utmost 
capacity  so  that  their  walls  become  fuUy  distended  and  remain  so 
until   the   end    of   the    auricular    contraction.     Directly   thereafter, 


THE  ARRANGEMENT  OF  THE  MUSCULATURE  OF  THE  HEART   271 


however,  the  ventricular  wall  recoils  and  exerts  a  static  pressure  upon 
the  blood  with  which  this  cavity  is  now  filled.  Secondary  currents 
are  set  up  which  strike  the  surfaces  of  the  valve  flaps  and  push  them 
upward  in  the  direction  of  their  position  of  closure.  This  static 
back  pressure,  however,  is  not  the  only  factor  upon  which  the  approxi- 
mation of  the  valve  flaps  depends ;  in  fact,  it  merely  serves  the  purpose 
of  "floating"  them  into  their  initial  position  of  closure,  while  the  actual 
snapping  together  of  their  marginal  areas  is  accomplished  by  the 
suction  which  must  necessarily  result  in  the  wake  of  the  column  of 
auricular  blood  as  it  clears  the  auriculoventricular  orifice.^  When 
the  contraction  of  the  auricles  ceases,  the  driving  force  is  suddenly' 
withdrawn.  The  column  of  blood,  however,  rushes  on,  with  the 
result  that  an  area  of  negative  pressure  is  developed  in  the  rear  of  it 
which  immediately  draws  the  flaps 
almost  transversely  across  the  center 
of  the  orifice.  Thus,  it  will  be  seen 
that  the  final  closure  of  the  valves  is 
accomphshed  by  the  "breaking"  of 
the  column  of  auricular  blood  and 
clearly,  as  the  flaps  swing  in  from  the 
side,  the  blood  is  cut  off  very  .sharply 
so  that  a  backward  movement  of  it  is 
impossible  under  ordinary  conditions. 

The  Semilunar  Valves. — The  con- 
ditions met  mth  at  the  aortic  and 
pulmonaiy  orifices,  are  quite  different 
from  those  encountered  at  the  auriculoventricular  openings.  In  ac- 
cordance with  the  high  degree  of  pressure  developed  by  the  ventricles, 
their  exits  are  narrow  and  surrounded  by  sohd  walls.  Each  orifice  is 
guarded  by  three  separate  segments  which  are  fastened  end  to  end 
against  the  internal  surface  of  these  blood-vessels.  Each  segment 
exhibits  a  cup-hke  shape,  its  convex  surface  being  directed  toward  the 
heart.  The  basal  portions  of  the  flaps  rest  upon  a  solid  cushion  of 
the  ventricular  substance,  while  their  free  ends  project  far  into  the 
lumen  of  the  blood-vessel.  No  special  structures  are  present  to  hold 
them  in  place. 

When  the  ventricles  contract  and  drive  the  blood  through  these 
sHt-like  orifices  into  the  arteries,  the  tips  of  the  different  valve-flaps 
are  pushed  far  apart,  but  it  should  be  emphasized  that  they  are  not 
forced  into  contact  with  the  wall  of  the  blood-vessel.  ^  Such  a  result 
is  practically  impossible,  because  the  basal  portions  of  the  flaps  are 
well  protected  against  the  ventricular  stream  by  the  heavy  cushion 
of  muscle  tissue  to  which  they  are  fastened,  and  because  the  beginning 
segment  of  each  blood-vessel  is  very  much  larger  than  its  more  periph- 

^  Henderson,  Am.  Jour,  of  Physiol.,  xvi,  1906,  325;  also  see:  Henderson  and 
Johnson,  Heart,  iv,  1912,  69. 

-  Ceradini,  Der  Mechanismus  der  halbmondf.  Klappen,  Leipzig,  1872. 


Fig.  134. — LoNGnuDrNAL  Section 
Thhough  the  Root  op  the  Aorta  to 
Show  Cup-like  Shape  of  Semilunar 
Valve  Flaps. 


272 


THE    MECHANICS    OF    THE    HEART 


eral  segment.  The  latter  peculiarity  is  dependent  upon  the  fact 
that  the  wall  opposite  each  valvular  segment  is  distended  to  form  a 
pocket,  the  so-called  sinus  of  Valsalva.^  A  certain  quantity  of  residual 
blood  is  always  retained  in  these  enlargements.  From  the  right  and 
left  fossae  arise  the  two  coronary  arteries  which  supply  the  substance 
of  the  heart. 

The  semilunar  valves  are  closed  directly  after  the  completion  of 
the  contraction  of  the  ventricles.  The  mechanism  involved  in  this 
process  is  smiilar  to  that  described  previously.     As  the  basal  portions 

of  the  different  segments  are  relatively 
fixed,  their  free  tips  are  snapped  to- 
gether by  the  "breaking"  of  the  ven- 
tricular jet  of  blood.  The  flaps  are 
then  held  firmly  together  by  the  pres- 
sure existing  in  the  arteries.  As  is 
indicated  in  Fig.  135,  this  force  is  di- 
rected not  only  in  a  straight  line 
against  their  outer  surfaces,  but  also 
transversely  against  their  marginal 
zones.  In  this  way,  the  under  sur- 
faces of  their  tips  are  forced  firmly 
against  one  another  so  that  a  displace- 
verse  section:  V.  ventricle;  A,  aorta;  ment  and  inversion  of  the  Segments 
FV,    fossa    of   Valsalva;  c,  corpora    -g       -^^  hnpossible.     Moreover,  it  is 

arantu.  7  '■  '      . 

oi  mterest  to  note  that  the  margmal 
area  of  the  tip  of  each  flap  gives  lodgment  to  a  fibrous  thickening 
which  rises  above  the  general  surface  and  is  adjusted  in  such  a  way 
that  it  closely  fits  into  the  neighboring  nodules.  In  this  way,  even 
the  most  central  regions  of  these  arterial  orifices  are  made  perfectly 
secure  when  the  valves  are  closed.  These  granular  bodies  are  known 
as  the  corpora  Arantii.^ 


Fig.  135. — Dl^graii  to  Show  Posi- 
tion OF  Semiluxah  Valve  Flaps  ox 
Closure. 

/,  longitudinal   section;  II,    trans 


CHAPTER  XXV 


THE  CARDIAC  CYCLE  (REVOLUTIO  CORDIS) 

The  Number  of  Cardiac  Cycles. — The  blood  reaches  the  venous 
vestibule  of  the  heart  under  a  veiy  low  pressure  and  leaves  its  arterial 
orifices  under  a  relatively  high  pressure.  This  fact  shows  that  this 
organ  acts  as  a  pump.  It  develops  one  of  the  fundamental  attributes 
of  the  circulation,  namely,  the  pressure  necessarj^  to  drive  the  blood 

'  Named  after  the  Italian  anatomist  Valsalva  of  Bologna,  born  in  1666. 
^  Named  after  Julius  Caesar  Aranzi  of  Bologna,  an  Italian  anatomist,  bom 
in  1530. 


THE    CARDIAC    CYCLE    (rEVOLUTIO    CORDIS)  273 

through  the  S3^stem.  Its  action,  however,  is  not  comparable  to  that 
of  a  piston-pump,  but  rather  to  that  of  a  rubber  bulb  when  compressed 
by  the  hand.  The  contraction  of  its  muscular  suV)stance  diminishes 
the  size  of  its  cavities  so  that  the  blood  contained  therein  is  subjected 
temporarily  to  a  high  degree  of  pressure.  Each  contraction  of  the 
heart,  or  systole,  is  immediately  followed  by  a  period  of  relaxation,  or 
diastole,  and  the  latter  in  turn  by  a  period  of  rest.  These  three  phases 
together  constitute  the  cardiac  cycle. 

The  general  rule,  that  the  frequency  of  the  heart  is  indirectly 
proportional  to  the  size  of  the  body,  finds  its  application  throughout 
the  animal  kingdom,  but  particularly  among  the  warm-blooded  ani- 
mals.    This  fact  is  clearly  brought  out  by  the  following  compilation: 

Elephant 25  cycles  in  a  minute 

Camel 30  cycles  in  a  minute 

Lion,  horse,  ox 40  cycles  in  a  minute 

Donkey 50  cycles  in  a  minute 

Panther 60  cycles  in  a  minute 

Sheep 70  cycles  in  a  minute 

Man 70  cycles  in  a  minute 

Dog 100  cycles  in  a  minute 

Rabbit 150  cycles  in  a  minute 

Mouse 175  cycles  in  a  minute 

Among  the  cold-blooded  animals  this  relationship  is  not  always 
apparent,  because  their  bodily  functions  are  more  markedly  influenced 
by  outside  conditions.  The  heart  of  the  frog  or  turtle  beats  40  to  50 
times  in  a  minute,  a  rather  slight  frequency  for  such  small  animals. 
The  fact  that  the  cardiac  frequency  is  greater  in  small  animals,  need  not 
surprise,  because  their  metaboUsm  is  greater  on  the  whole  than  that  of 
larger  animals.  This  must  necessaril}-  be  so,  because  as  the  former 
present  a  proportionately  larger  surface  to  the  medium  in  comparison 
with  their  mass,  they  must  lose  larger  amounts  of  heat.  This  greater 
loss  is  counteracted  by  more  intense  metabohc  changes. 

The  human  heart  is  subject  to  various  influences,  such  as  age,  sex, 
temperature,  barometric  pressure,  posture,  muscular  movements, 
emotions,  etc.  Before  birth,  the  heart  of  the  female  beats  about  140 
to  145  times  in  a  minute,  and  that  of  the  male  about  130  to  135  per 
minute.  Conditions  being  favorable,  it  is  posible  to  make  use  of  this 
fact  in  foretelling  the  sex  of  the  fetus.  It  is  still  very  frequent  at 
birth,  but  its  rate  is  markedly  decreased  during  the  first  year  of  extra- 
uterine hfe  and  more  gradually  during  the  subsequent  years.  Late  in 
life  its  frequency  is  again  increased. 

At  birth 140 

Infancy 120 

Childhood 100 

Youth 90 

Adult  age 75 

Old  age 70 

Extreme  old  age 75-80 

18 


274  THE  MECHANICS  OF  THE  HEART 

On  account  of  the  larger  size  of  the  male  body,  the  heart  of  the 
male  is  less  frequent  than  that  of  the  female,  but  if  a  comparison 
is  made  between  men  and  women  of  equal  size,  no  significant  differ- 
ences will  be  found.  The  figures  ordinarily  given  for  man  are:  70 
beats  in  the  male,  80  in  the  female,  and  90  in  children.  Even  very 
slight  muscular  movements  increase  the  rate,  while  rest  decreases 
it,  the  lowest  value  being  found  after  continued  quietude  in  the  hori- 
zontal position.  On  assmning  the  erect  position  the  heart  beats  some- 
what faster.  The  figures  frequently  given  are:  75  on  lying  down,  77 
on  sitting  up,  and  85  on  standing  erect.  Its  frequency  is  also  aug- 
mented by  warm  food,  or  by  increasing  the  temperature  of  the  sur- 
rounding medium.  The  same  result  is  obtained  if  the  temperature  of 
the  bod}',  as  a  whole,  is  raised,  as  in  fever.  This  augmentation  may 
be  shown  very  clearly  by  perfusing  the  heart  of  a  cold-blooded  animal 
with  Ringer's  solution  which  it  is  possible  to  heat  gradually.  The 
force  and  rate  of  the  heart  beat  then  increase  with  the  temperature 
until  a  maximum  has  been  reached  at  about  30°  C.  Beyond  this  point 
the  beats  become  slower  and  assume  an  irregular  and  fibrillar  character 
until  they  stop  entirely.  Very  similar  tests  have  been  made  by  N. 
Martin  upon  the  heart  of  the  cat.  This  organ  ceases  to  beat  at  about 
17°  C.  and  also  if  the  temperature  of  the  perfusing  liquid  is  raised  to 
44°  or  45°  C.  The  acceleration  obtained  during  fever  may,  therefore, 
be  due  in  large  part  to  the  direct  action  of  the  blood  as  it  traverses 
the  cardiac  chambers.  Most  generally,  the  heart  of  warm-blooded 
animals  beats  more  quickly  and  more  strongly  during  the  cold  seasons 
of  the  3^ear,  which  change  is  in  agreement  with  the  fact  that  their 
metabolic  activity  is  greater  in  winter  than  in  summer.  The  reduced 
metabohsm  and  heat  production  coincident  with  low  degrees  of  tem- 
peratm'e  must  be  held  responsible  for  the  decided  decrease  in  the  fre- 
quency of  the  heart  of  hibernating  animals.  In  the  bat,  for  example, 
a  frequency  of  28  in  a  minute  during  this  period  gives  way  to  200 
per  minute  during  the  summer  months.  Muscular  exercise  increases 
the  frequency  of  the  heart,  because  the  tissues  then  undergo  more  in- 
tense metabolic  changes  and  require  a  more  copious  supply  of  blood. 
Decreases  in  the  oxygen  content  or  increases  in  the  carbon  dioxid  con- 
tent of  the  blood  increase  the  rate. 

The  Character  of  the  Contraction. — Attention  has  already  been 
called  to  the  fact  that  the  different  segments  of  the  heart  do  not  con- 
tract simultaneously,  but  successively,  the  musculature  nearest  the 
venous  vestibule  being  activated  first  and  that  nearest  the  apex  last 
of  all.  Thus,  the  contraction  of  this  organ  presents  severaKof  the 
characteristics  of  a  peristaltic  wave,  progressing  from  its  base  to  its 
apex.  For  this  reason,  it  has  been  said  to  be  similar  in  character  to  the 
curve  recorded  by  skeletal  muscle  when  stimulated  with  a  tetanic 
current.  This  fact  proves  that  the  cardiac  musculature  remains  in 
the  state  of  systole  for  some  moments  before  it  again  relaxes.  Clearly, 
this  peculiarity  in  the  manner  of  its  contraction  must  tend  to  produce  a 


THE    CARDIAC    CYCLE    (rEVOLUTIO    CORDIS)  275 

thorough  emptying  of  the  different  chambers  of  the  heart.  But,  as  it 
has  been  shown  that  single  narrow  segments  of  cardiac  muscle  giv(! 
typical  twitch-like  contractions,  it  must  be  concluded  that  the  tetanic 
character  of  the  systolic  movem(!nt  of  the  entire  organ  can  only  be 
due  to  the  fact  that  its  different  segments  contract  successively  in 
the  direction  from  base  to  apex.* 

The  Speed  of  the  Contraction  Wave. — The  progressive  character 
of  the  contraction  of  the  heart  may  be  studied  best  in  the  lower  forms 
in  which  the  systole  of  the  sinus  antecedes  that  of  the  auricle,  and  the 
systole  of  the  latter  that  of  the  ventricle.  In  a  similar  way  it  may  be 
observed  in  the  mammalian  heart  that  the  auricular  contraction  is 
separated  from  the  ventricular  by  a  definite  interval  which  becomes 
especially  noticeable  in  an  organ  shortly  before  it  ceases  to  beat. 
A  graphic  record  of  the  contraction  wave  may  be  made  by  placing 
long  writing  levers  upon  the  basal  and  apical  portions  of  an  exposed 
heart.  If  these  levers  are  permitted  to  write  in  the  same  vertical  line 
and  in  relation  with  a  chronograph  registering  the  time  in  seconds,  it 
is  a  simple  matter  to  compute  its  speed,  because  the  distance  between 
the  levers  can  be  measured  directly  with  a  ruler.  In  this  way,  it  has 
been  found  by  Reid  and  Waller-  that  the  velocity  of  this  wave  is  10  cm. 
in  a  second  in  the  heart  of  the  frog  and  80  cm.  per  second  in  that  of  the 
sheep.  Bayliss  and  Starhng-^  give  the  value  of  300  cm.  in  a  second  for 
the  dog's  heart.  In  accordance  with  these  figures,  it  must  be  con- 
cluded that  the  wave  consumes  at  least  0.05  sec.  in  its  passage  across 
the  human  heart.  In  fact,  upon  the  basis  of  electrical  measurements 
made  by  Kraus  and  Nicolai,^  an  even  longer  time  seems  to  be  required, 
namely  about  0.2  sec,  before  the  distalmost  segments  of  the  ventricles 
become  involved. 

The  Path  of  the  Contraction  Wave. — In  the  mammalian  heart,  the 
musculature  of  the  ventricles  is  completely  separated  from  that  of  the 
auricles  by  a  zone  of  fibrous  tissue.^  At  one  point,  however,  the  two 
masses  are  connected  by  a  strand  of  modified  muscle  tissue  which  is 
known  as  the  bundle  of  His^  or  the  auriculoventricular  bundle.  This 
bridge  begins  in  the  basal  portion  of  the  interauricular  septum,  di- 
rectly above  the  septum  fibrosum  atrioventriculare.  It  arises  in  a 
complex  nodular  accumulation  of  cells  and  fibers  which  is  usually  re- 

1  Walther,  Pfltiger's  Archiv,  Ixxviii,  1900,  597. 
2Phila.  transactions,   198,   1888,  230. 

3  Proc.  Royal  Soc,  1892,  211. 

4  Berliner  Klin.  Wochenschr.,  1907,  Nr.  25  and  27. 

*  It  has  been  known  for  some  time  that  muscular  connections  between  the 
auricles  and  ventricles  are  present  in  the  fish,  reptiles  and  amphibians.  The 
existence  of  similar  connections  in  mammals  has  been  denied  until  1893,  when 
G.  Paladino  and  Stanley  Kent  put  forth  the  claim  that  a  path  of  this  kind  exists. 
Their  observations,  however,  cannot  be  regarded  as  valid,  because  their  descriptions 
are  very  indefinite,  while  the  illustrations,  showing  certain  connections  between  the 
left  auricle  and  ventricle,  apparently  do  not  picture  the  conditions  as  they  actually 
are. 

«  Named  after  W.  His,  Jr.  (1893),  Professor  of  Anatomy  at  Leipzig  (1863). 


276  THE    MECHANICS    OF    THE    HEART 

ferred  to  as  the  auriculoventricular  node.  Having  pierced  the  fibrous 
tissue  of  the  groove,  it  passes  along  the  interventricular  septum  immedi- 
ately below  the  endocardium,  and  divides  eventually  into  two  branches. 
This  bifurcation  takes  place  at  about  the  point  where  the  posterior 
and  median  flaps  of  the  aortic  valve  are  joined.  The  main  bundle  of 
the  average  hmnan  heart  is  about  18  mm.  in  length  and  1.5  to  2.5  mm. 
in  width.  One  of  its  branches  is  distributed  to  the  right,  and  the  other 
to  the  left  ventricle,  but  before  the  distant  musculature  is  reached,  the 
bundle  spreads  out  fan-like  and  forms  an  intricate  network  of  fibers. 
This  peripheral  ramification  was  clearly  recognized  by  Purkinje,  but 
no  particular  attention  was  paid  to  it  until  Tawara^  proved  that  its 
constituents  are  intimatelj^  connected  with  the  bundle  of  His. 


Fig.  136.— Left  Vextricle  Laid  Opex  to  Displ-^y  the  Ls-TERVEXTRicrL.tR  Septi-m. 
The  Course  of  the  Auriculovextrictlar  BrxDLE  axd  Its  ILoiificatioxs  are  Showx 
IX  Black.     (After  Tawara.) 

It  has  previously  been  stated  that  in  the  lower  animals  the  contrac- 
tion wave  originates  in  the  sinus  venosus,  and  eventuallj-  reaches  the 
apex  of  the  ventricle  by  travelling  across  bridges  of  muscle  tissue. 
The  sinus,  therefore,  must  give  lodgment  to  a  certain  group  of  cells 
in  which  the  wave  of  excitation  is  generated.  For  this  reason,  this 
particular  area  of  the  sinus  has  been  designated  as  the  pacemaker  of 
the  heart. 

Very  similar  conditions  are  met  with  in  the  mammals.  Thus,  the 
embryonic  heart  presents  the  sinus  venosus  as  a  separate  cavity  which 
is  bounded  by  the  orifices  of  the  vense  cavae,  the  Eustachian  valve  and 
the  interauricular  septmn.  The  adult  organ,  on  the  other  hand,  does 
not  possess  a  distinct  vestibular  enlargement,  because  the  sinus  has 
been  incorporated  in  the  main  cavity  of  the  auricle.  The  remnants 
of  the  Eustachian  and  venous  valves,  however,  are  still  discernible 
in  conjunction  with  the  tsenia  terminahs.  Even  a  very  casual  observa- 
1  Pfliiger's  Archiv,  cii,  1906,  300. 


THE  CARDIAC  CYCLE  (rEVOLUTIO  CORDIS)        277 

tion  of  the  beating  iiiainmalian  lieart  must  show  that  the  contractions 
begin  in  the  tissue  situated  at  tht;  junction  of  the  superior  vena  cava 
with  the  right  auricle.  This  region  which  corresponds  to  the  sinus 
reuniens  of  the  embryonic  organ,  constitutes  the  pacemaker  of  the 
higher  type  of  hearts.  One  of  these  veno-auricular  accumulations 
of  tissue  has  been  adequatel}^  descril^ed  by  Wenkelbach.  In  confii-ma- 
tion  of  this  work,  Flack  and  Keith ^  have  applied  to  this  area  the  name 
of  sino-auricular  node,  the  further  assertion  being  made  by  these  in- 
vestigators that  it  is  intimately  connected  with  the  bundle  of  His. 
It  must  be  concluded,  therefore,  that  the  stimulus  to  contract 
arises  in  the  specialized  tissue  forming  the  sino-auricular  node.     When 


Fig.  137. — The  Auriculoventricular  Bundle  and  its  Terminal  Ramifications 
IN  THE  Interior  of  the  Ventricles  (from  Model  Constructed  by  Miss  De  Witt 
ON  Basis  of  Dissections). 

The  di\'ision  of  the  bundle  into  right  and  left  branches  is  shown,  and  the  ramifications 
of  each  of  these  branches  in  the  interior  of  the  right  and  left  ventricles.  The  branching 
system  in  the  left  ventricle  is  incomplete  in  the  model,  as  the  outer  wall  of  this  ventricle 
had  been  removed  in  the  dissection.     {Howell.) 

this  area  is  warmed  or  cooled,  the  frequency  of  the  heart  as  a  whole  is 
either  increased  or  decreased;  and  this  effect  cannot  be  produced  if 
other  regions  of  this  organ  are  subjected  to  changes  in  temperature. ^ 
Furthermore,  it  has  been  found  by  GaskelP  that  the  rhythmic  power 
of  the  muscle  tissue  of  the  venous  vestibule  is  greater  than  that  of  the 
ventricular  musculature. 

The  wave  of  excitation  is  propagated  from  the  sino-auricular  node 
to  the  different  segments  of  the  auricles  as  well  as  to  the  auriculoven- 
tricular node.     Although  the  statement  is  generally  made  that  the 

^  Jour,  of  Anat.  and  Phj-siol.,  xli,  1906,  172,  and  M.  Flack,  Jour,  of  Physiol., 
xli,  1910,  64. 

^  Erlanger  and  Blackman,  Am.  Jour,  of  Physiol.,  xix,  1907,  125;  also  see: 
Schlomovitz  and  Chase,  Am.  Jour,  of  Physiol.,  xli,  1916,  112. 

3  Schafer's  Textbook  of  Physiol.,  1900. 


278  THE  MECHANICS  OF  THE  HEART 

auricles  contract  together,  accurate  measurements  have  shown  that 
the  left  one  lags  somewhat  behind  the  right.  The  interval,  of  course, 
is  extremely  brief;  it  amounts  to  only  0.01  to  0.03  sec.  The  excitation 
wave  finally  reaches  the  papillary  bases  of  the  ventricles  by  way  of  the 
bundle  of  His  and  its  distal  ramifications.  The  wave  itself  is  accur- 
ately timed  so  that  a  perfect  coordination  between  the  different  seg- 
ments of  the  heart  is  assured.  We  have  previously  noted  that  a  period 
of  almost  0.2  sec.  elapses  before  the  wave  arrives  in  the  distalmost 
muscle  strands  of  the  ventricle,  but  naturally,  the  conduction  is  not 
equally  rapid  in  all  parts  of  the  heart.  Thus,  it  has  been  found  that 
the  bundle  of  His  conducts  rather  slowly,  because  the  wave  attains 
here  a  velocit}^  of  only  10  to  15  cm.  in  a  second.  This  fact  is  of  interest, 
because,  as  has  previously  been  shown,  the  ventricle  contracts  after 
the  auricle,  the  interval  between  their  systoles  amounting  to  0.12-0.2 
sec.  Hence,  the  resistance  in  this  bridge  of  tissue  has  been  adjusted 
in  such  a  way  that  a  perfect  sequence  of  contraction  is  obtained. 

Two  views  are  held  regarding  the  manner  in  which  the  ventricular 
musculature  is  activated.  It  was  formerly  believed  that  the  segments 
situated  nearest  the  auriculoventricular  groove,  contract  first,  while 
those  closest  to  the  apex  are  involved  last.  The  results  of  electrical 
measurements  and  of  cinematographic  records  of  the  beating  heart, 
taken  by  Nicolai  and  others,^  however,  have  shown  that  the  excitation 
wave  is  conducted  directly  to  the  papillary  projections,  and  hence,  it 
must  be  concluded  that  this  particular  system  of  the  ventricles  is 
activated  first.  The  contraction  wave  spreads  from  here  to  the  oblique 
and  circular  muscle  fibers.  Clearly,  this  view  is  entirely  in  accord  with 
the  anatomical  arrangement  of  the  conducting  path,  because,  as  has 
been  stated  above,  the  main  bundle  of  His  is  enveloped  in  a  sheath  of 
fibrous  tissue,  while  its  terminals,  the  fibers  of  Purkinje,  are  directly 
traceable  to  the  papillary  muscles. 

Heart-block. — The  preceding  statements  find  amphfication  in  the 
observations  of  Gaskell,^  showing  that  the  passage  of  the  wave  of  excita- 
tion through  the  hearts  of  frogs  and  turtles  may  be  greatly  retarded  by 
compressing  the  tissue  forming  the  auriculoventricular  groove.  While 
this  end  may  be  attained  with  the  help  of  a  pair  of  forceps,  a  better  way 
is  to  adjust  a  screw-clamp  to  this  region,  which  enables  the  experimenter 
to  grade  the  pressure  more  accurately  and  to  obtain  different  degrees 
of  blocking.  Under  ordinary  conditions  every  contraction  of  the  auri- 
cles is  followed  by  a  contraction  of  the  ventricles,  because  the  wave 
of  excitation  meets  with  no  obstacle  in  its  passage  through  the  bundle. 
If  the  latter  is  now  thoroughly  compressed  by  the  closure  of  the  clamp, 
the  impulse  is  blocked  at  the  seat  of  the  injury  and  cannot  reach  the 
ventricles.  This  particular  segment  of  the  heart  now  ceases  to  beat, 
while  the  auricular  portion  continues  its  activity  as  previously  estab- 

^  Braun    (Herzbewegung   und    Herzstoss,    Fisher,    Jena,    1898),  and    Rehfish 
(Berliner  klin.  Wochenschr.,  1908,  Nr.  26). 
2  Jour,  of  Physiol.,  iv,   1883,  66. 


THE    CARDIAC    CYCLE    (liEVOLUTIO    CORDIS)  279 

lished.  Eventually,  however,  the  ventricle  develops  a  rhythm  of  its 
own  which  is  made  possible  Ijy  its  inherent  power  of  contraction. 
This  condition  constitutes  total  heart-block.  It  must  be  remembered, 
however,  that  there  are  also  certain  intermediate  stages  of  this  affec- 
tion which  arise  whenever  the  obstruction  is  not  complete.  This  en- 
ables the  wave  of  excitation  to  break  through  at  intervals.  Thus,  it 
may  come  to  pass  that  only  every  second,  or  every  third  or  fourth 
auricular  systole  is  able  to  elicit  a  regular  ventricular  contraction, 
thus  establishing  a2:l,  3:1,  or4:l  rhythm.  In  other  words,  while 
one  single  wave  may  not  be  sufficiently  powerful  to  overcome  the  re- 
sistance placed  in  the  path  of  condu(;tion,  the  sum  total  of  two  or  three 
or  more  may  suffice  to  break  through  this  obstruction.  And  naturally, 
whenever  the  ventricle  is  thus  made  to  respond  to  an  auricular  beat, 
the  resulting  systole  must  exhibit  the  characteristics  of  a  normal 
contraction,  because  under  ordinary  conditions,  the  activity  of  cardiac 
muscle  docs  not  vary  with  the  strength  of  the  stimulus,  but  remains 
constant. 

It  has  been  stated  by  Kent^  that  these  observations,  although  origi- 
nally made  upon  the  heart  of  the  frog,  may  be  duplicated  in  mammals, 
but  the  evidence  submitted  in  support  of  this  statement  cannot  be  re- 
garded as  at  all  convincing.  In  conformity  with  the  work  of  Wool- 
dridge  and  Tigerstedt,^  it  has  been  found  by  His  that  the  auricles  and 
ventricles  may  be  functionally  dissociated  not  only  by  destroying  the 
interauricular  septum,  but  also  by  causing  a  local  injury  to  the  auric- 
uloventricular  bundle.  These  results  have  been  confirmed  and  much 
extended  by  Erlanger.^  In  man,  heart-block  commonly  arises  in  con- 
sequence of  endocardial  lesions  or  tumors  involving  the  origin  and  main 
strand  in  the  bundle  of  His.  It  may  also  be  caused  by  a  general 
diminution  in  the  irritability  of  the  ventricular  musculature,  a  con- 
dition which  may  result  in  the  course  of  syphilis  and  septic  infections 
and  intoxications. 

Fibrillation  of  the  Cardiac  Muscle  (Delirium  Cordis). — When 
in  fibrillation,  the  musculature  does  not  respond  with  strong  and 
unified  contractions,  but  with  a  continuous  wavy  and  oscillatory 
motion.  This  condition  may  be  more  or  less  localized  or  may  affect 
the  organ  as  a  whole.  When  restricted  to  the  auricles,  as  it  frequently 
is,  it  is  designated  as  auricular  fibrillation,  and  when  involving  the 
ventricles,  as  ventricular  fibrillation.  It  follows  strong  electrical, 
thermal,  or  mechanical  stimulation  of  the  cardiac  muscle  as  well  as 
obstructions  to  the  coronary  circulation.  It  is  scarcely  possible  to 
relieve  this  condition  after  it  has  been  firmly  established.  In  this 
regard,  it  differs  from  the  so-called  flutter  which  signifies  an  extreme 
increase  in  frequency,  sometimes  to  300  or  400  in  a  minute  without 
marked  alteration  in  the  character  of  the  individual  beats. 

1  Jour,  of  PhvsioL,  xiv,  1893,  233. 

2  Archiv  fiir  F'hysiol.,  1883  and  1884. 

3  Am.  Jour,  of  Physiol.,  xvi,  1906,  160;  and  xxx,  1912,  395. 


280  THE  MECHANICS  OF  THE  HEART 

The  cause  of  this  sudden  loss  of  regularity  of  contraction  is  not 
fully  understood.  Kronecker^  believes  that  it  is  due  to  the  destruction 
of  the  coordinating  cardiac  center,  while  McWilliam^  states  that  it  is 
dependent  upon  an  interference  with  conduction.  The  work  of  Gar- 
rey^  has  greatly  strengthened  the  block-hypothesis  of  Porter"*  which 
proposes  that  the  fibrillation  is  due  to  an  interruption  of  the  contrac- 
tion wave.  In  consequence  of  this  blocking,  this  wave  is  prevented 
from  running  its  usual  course  until  the  normal  coordinated  action  of 
the  cardiac  musculature  gives  way  to  the  confused  "circus"  motions 
of  fibrillation.  A  similar  confusion  of  contraction  may  be  produced 
in  the  tongue  by  reestablishing  the  circulation  after  it  has  been  inter- 
rupted for  some  time.  As  this  organ  embraces  muscle  fibers  which  are 
arranged  in  different  directions,  it  has  been  thought  that  this  peculiar 
motion  is  caused  by  a  loss  of  functional  continuity  between  the  adjoin- 
ing areas  of  tissue.  It  is  possible  that  a  similar  dissociation  takes 
place  in  the  fibrillating  heart. 

A  fibrillating  heart,  or  ventricle,  is,  of  course,  quite  unable  to  expel 
the  blood  and  to  sustain  the  circulation.  Death  results  very  sud- 
denly. A  fibrillating  auricle,  on  the  other  hand,  is  not  necessarily 
incompatible  with  life,  because  the  ventricles  are  still  in  a  condition  of 
responding.  To  be  sure,  the  contractions  of  the  latter  become  irregu- 
lar, because  they  are  now  played  upon  by  numerous  impulses  derived 
from  the  fibrillating  auricles.  This  condition  is  characterized  by  an 
irregular  arterial  pulse  and  an  absence  of  the  auricular  summit  from 
the  venous  pulse,  as  recorded  from  the  external  jugular  vein.  The 
electrocardiogram  taken  at  this  time  does  not  show  the  P-wave  which 
represents  the  electrical  variation  produced  by  the  normally  acting 
auricles. 


CHAPTER  XXVI 
THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE 

The  different  cardiac  cycles  follow  one  another  in  rapid  succession, 
every  additional  one  adding  another  unit  of  work  to  that  already 
accomplished.  Like  any  other  mass  of  hving  substance,  cardiac 
muscle  generates  mechanical,  thermal,  and  electrical  energy.  The 
first  of  these  is  at  present  of  greatest  interest  to  us,  because  it  furnishes 
the  basis  for  the  dynamics  of  the  circulation.  While  the  heart  is  en- 
gaged in  this  process  of  kinetically  innervating  the  blood,  it  exhibits 

1  Compt.  rend.,  Soc.  de  Biol,  1891. 
•     2  Jour,  of  Phvsiol.,  viii,  1887. 

3  Am.  Jour,  of  Physiol.,  xxi,  1908,  283. 
*  Ibid.,  vi,  1902,  25. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  281 

a  number  of  phenomena  which  may  be  conveniently  dealt  with  under 
the  following  headings:  (a)  the  changes  in  its  form,  (b)  the  generation 
of  electrical  energy,  (c)  the  production  of  sounds,  id)  the  variations 
in  pressure  within  its  chambers,  and  (e)  the  changes  in  the  position  of 
its  valves. 

A.  THE  CHANGES  IN  THE  FORM  OF  THE  HEART 

Methods  of  Registration. — The  procedures  most  frequently  em- 
ployed for  determining  the  changes  which  the  heart  undergoes  during 
its  systohc  and  diastolic  phases,  may  be  arranged  in  the  following 
manner : 

(o)  Observation  with  the  help  of  hnear  measuring  instruments.  (Ludwig, 
1843.) 

(6)  Graphic  registration  by  means  of  ordinary  writing  levers  which  are  placed 
horizontally  upon  different  parts  of  the  heart  (von  Frey),  or  with  the  help  of 
suspended  levers  which  are  connected  with  the  cardiac  musculature  by  strings. 
(Gaskell,  18S2,  and  Engelmann,  1892.) 

(c)  Photographic,  cinematographic,  and  radiographic  registration.  Ortho- 
diagraph.    (Zuntz  and  Schumberg,  1896,  Buchard,  1898,  and  Braun,  1898.) 

{d)  Acupuncture,  the  insertion  of  long  needles  into  different  regions  of  the 
heart  while  the  chest  remains  closed.     (Jung,  1836,  and  Haycroft,  1890.) 

Nearly  all  investigations  of  this  kind  have  been  made  either  upon 
the  excised  heart  or  upon  the  heart  while  freely  exposed  to  the  view 


Fig.   138. — Diagram  to  Show  How  the  Beating  Frog's  Heart  Adapts  Itself  to  the 
Surface  Upon  Which  It  Rests.     The  Dotted  Line  Indicates  Diastole. 

by  removing  the  ventral  wall  of  the  thorax.  Quite  obviously,  either 
one  of  these  procedures  cannot  be  regarded  as  perfect,  because  it 
places  this  organ  under  abnormal  conditions  and  tends,  therefore, 
to  disturb  its  normal  activity.  At  the  present  time,  however,  this  diffi- 
culty cannot  be  avoided  and  hence,  it  becomes  necessary  to  correct 
any  errors  from  this  source  by  indirect  evidence.  Inasmuch  as  the 
consistency  of  the  cardiac  substance  is  soft  during  diastole  and  firm 
during  systole,  the  organ  as  a  whole  must  necessarily  adapt  itself  to 
its  surroundings  and  undergo  certain  changes  in  its  form  which,  so  to 
speak,  are  forced  upon  it.  Even  the  normal  heart  in  situ  is  not  fully 
protected  against  the  different  degrees  of  traction  which  are  brought 
to  bear  upon  it  whenever  the  body  as  a  whole  is  made  to  assume  an 
unusual  position. 

.  In  endeavoring  to  obtain  a  composite  picture  of  the  changes  in  the 
form  of  the  beating  heart,  attention  should  first  be  called  to  the  altera- 


282 


THE    MECHANICS    OF    THE    HEART 


tions  in  its  shape,  and  secondly,  to  the  alterations  in  its  position. 
Concerning  the  former,  the  general  statement  may  be  made  that  its 
longitudinal  and  transverse  diameters  are  decreased  during  systole, 
wliile  its  anteroposterior  diameter  is  increased.  In  this  way,  the  base 
and  apex  of  the  organ  are  brought  closer  together,  while  the  outline 
of  its  basal  portion  is  changed  from  an  eUipse  to  a  circle.  For  this 
reason,  a  diastolic  heart  alwa3's  appears  to  be  thicker  along  its  borders 
than  near  its  center,  while  the  organ  as  a  whole  more  nearly  conforms 
to  the  general  outline  of  the  surface  upon  which  it  is  resting.  It  is 
also  evident  that  the  systolic  heart  executes  a  rotator>^  movement 
which  under  ordinary  conditions  of  experimentation  remains  more 
closely  confined  to  its  apical  portion.     In  accordance  with  our  previous 


-ShowusG  Location  of  Apex  Beat. 

The  position  of  the  aortic  gemilunar  (+)  and  mitral  (A)  valves  are  indicated  in  red 
and  that  of  the  pulmonary  semilunar  (+)  and  tricuspid  (A)  in  blue. 

observation  that  the  superficial  fibers  of  the  ventricle  pursue  in  general 
an  S-shaped  course  and  form  a  whorl  at  the  apex,  it  may  be  inferred 
that  the  rotation  takes  place  from  left  to  right. 

The  Cardiac  Impulse  (Impulsus  Cordis). — On  observing  the  exter- 
nal surface  of  the  chest  in  the  region  of  the  apex  of  the  heart,  it  is 
noticed  that  the  thoracic  wall  is  made  to  bulge  outward  with  every 
systohc  movement.  In  men,  the  greatest  prominence  is  attained  in 
the  fifth  intercostal  space  slightly  to  the  right  of  the  left  mammillary 
Une,  which  represents  the  perpendicular  drawn  through  the  left 
nipple.     In  woman,  this  impulse  is  more  frequently  observed  in  the 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  283 


Fig.     140. — Transverse     Section 

Throcgh   the    Chest   to    Show   the 

Changes  in  the  Shape  of  the  Base 

of  the  Heart  on  Systole. 

The  systolic  heart  (dotted  line)  lies 

closer  to  the  chest  wall. 


fourth  intercostal  space  and  is  not  so  clearly  betrayed  on  account  of 

the  interposition  of  a  layer  of  mammary  tissue.     The  area  so  affected 

measur(\s  about  2  cm.  in  diamotor. 
In  accordance  with  tiie  statements 

just    made,  it    is   possil)le   to   assign 

three  causes  to  this  impulse,  namely: 

(a)  the  change  in  the  outline  of  the 

basal   portion   of   the   heart,    (h)    the 

elevation  or  erection  of  the  ventricle, 

and  (c)  the  spiral  rotation  of  the  apex 

from   left  to  right  and  from   behind 

forward.     We    have    seen    that    the 

cross-section   of  the  base  of  the  dias- 
tolic heart  is  elliptical  while  that  of 

the  systolic  organ  is  circular.     This 

change,  as  is  clearl}^  portrayed  in  the 

accompanying     schema     (Fig.     140), 

tends  to  decrease  the  distance  between 

the  wall  of  the  thorax  and  the  anterior  surface  of  the  heart.  The  base 
of  the  organ  is  thus  moved  nearer  the  chest  wall.  It 
should  also  be  remembered  that,  in  man,  the  space 
intervening  between  the  heart  and  the  wall  of  the 
thorax,  is  filled  by  the  marginal  area  of  the  left  lung. 
As  this  organ  is  more  fully  distended  during  inspira- 
tion, its  border  is  forced  farther  forward  in  the  direc- 
tion of  the  median  line,  while  during  the  subsequent 
expiration  it  again  recedes  laterally.  It  may  be  in- 
ferred, therefore,  that  the  layer  of  pulmonary  tissue  in- 
terposed betw-een  the  heart  and  the  thoracic  wall,  is 
thinner  during  expiration  than  during  inspiration  and 
that  the  organ  as  a  whole  approaches  the  thoracic 
wall  more  closely  during  the  former  period.  For  this 
reason,  the  cardiac  impulse,  or  apex  beat,  is  more  con- 
spicuous during  expiration.  In  the  second  place,  it 
need  scarcely  be  emphasized  that  the  ventricle  is  more 
flaccid  when  relaxed  than  when  contracted,  so  that  its 
apex  must  assume  a  more  dependent  position  during 
the  former  period.  The  contraction  of  the  ventricle, 
therefore,  must  lead  to  an  elevation  of  the  apex  for- 
ward and  upward,^  because  the  base  of  the  organ  is 
naturally  more  firmly  anchored  than  its  apex  (Fig.  141). 
Thirdly,  this  upward  kick  of  the  ventricle  is  intensi- 
fied by  the  fact  that  the  apex  turns  slightly  around 
its  longitudinal  axis,  bringing  a  more  extensive  por- 
tion of  its  left  side  into  view.^ 

^  W.  Harvey,  "Cor  sese  erigere." 

^  W.  Harvey,  "lateralem  inclinationem." 


Fig.  14  1.— 
Longitudinal 
Section  Through 
the  Chest  to 
Show  the  For- 
ward and  Upw.vrd 
Movement  of  the 
Apex  During  the 
Systole  (Dotted 
Line)  of  the  Ven- 
tricles. 


284 


THE    MECHANICS    OF    THE    HEART 


In  accordance  with  the  observations  made  upon  the  excised  heart, 
it  may  seem  surprising  that  the  changes  in  the  different  diameters  of 
the  heart  do  not  cause  the  apex  to  be  displaced  in  an  ahnost  straight 
Hne  upward  toward  the  base.  Different  reasons  may  be  given  for  its 
relative  immobility.  While  it  must  be  granted  that  the  heart  is  more 
firmly  anchored  at  its  base  on  account  of  the  firm  support  afforded  it 
by  the  large  blood-vessels,  it  must  be  remembered  that  the  pericardial 
sac,  together  with  its  mediastinal  fastenings  to  the  diaphragm,  pos- 
sesses the  tendency  of  counteracting  any  distinct  displacement  of  the 
apex.  It  is  also  claimed  that  the  discharging  heart  suffers  a  recoil  in 
the  manner  of  a  cannon  on  being  fired, ^  and  secondly,  that  the  sudden 
distention  and  straightening  out  of  the  aorta  and  pulmonary  artery 
by  the  escaping  ventricular  blood  causes  the  basal  region  to  recede 
somewhat  in  a  downward  direction.  The  ventricle  being  thus  opposed 
by  a  resistance  above,  must  remain  in  its  former  position. ^ 


Fig.  142. — Cahdiograph. 
This  is  strapped  around  the  chest,  the  central  button  is  appHed  to  the  "apex-beat" 
and  its  pressure  on  the  chest  wall  regulated  by  means  of  the  three  screws  at  the  sides. 
The  tube  at  the  upper  part  of  the  instrument  serves  to  connect  the  drum  of  the  cardio- 
graph with  a  registering  tambour,  such  as  is  shown  in  Fig.  143.     (Sanderson.) 

The  Cardiogram. — A  graphic  record  of  the  cardiac  impulse  or 
apex  beat  may  be  obtained  with  the  help  of  two  Alarey  tambours, 
one  of  which  is  fastened  to  the  surface  of  the  chest  (Fig.  142)  in  the  area 
previously  designated,  and  the  other  upon  a  stand  in  relation  with  the 
smoked  paper  of  a  kymograph  (Fig.  143).  When  connected  bj-  means 
of  rubber  tubing,  the  membranes  of  these  tambours  must  oscillate  in 
unison.  If  the  membrane  upon  the  receiving  tambour  is  pressed  in- 
ward by  the  bulging  chest  wall,  the  writing  lever  attached  to  the  re- 
cording drum  must  move  upward,  and  vice  versa. 

This  instrument  is  known  as  the  cardiograph,  and  the  record  made 
by  it  as  the  cardiogram.     Not  much  importance  can  be  attached  to  it 

^  Skoda,  Abh.  iiber  Perc.  unci  Auskultation,  Wien,  1847,  also  see :  Feuerbach, 
Pflliger's  Archiv,  xiv,  1877. 

2  Sena,  Traitc  de  la  struct,  du  coeur.,  Paris,  1849,  or  Aufrecht,  Deutsch.  Arch, 
fiir  klin.  Med.,  Nr.  19,  1877. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  285 

as  a  means  of  diagnosis,  because  it  frequently  fails  to  represent  the 
conditions  as  they  actually  are.  It  must  l)e  granted,  however,  that  the 
fault  does  not  always  lie  with  the  instrument,  hut  more  frequently 
with  the  experimenter.  If  properly  applied,  it  registers  the  different 
beats  with  accuracy,  but  does  not  allow  definite  conclusions  being 
made  regarding  the  character  of  the  contractions,  because  its  mechan- 
ism is  easily  affected  by  vai'ious  factors  such  as  changes  in  the  position 
of  the  body,  or  alterations  in  the  resistance  under  which  it  is  made  to  act. 


Fig.   143. — Marey's  Tambouk. 
a.  Axis  of  lever;  h,  metal  tray  covered  with  rubber  membrane,  and  communicating 
by  tube  /  with  the  receiving  drum  shown  in  Fig.  142.     (Starlino-) 

Moreover,  the  conspicuousness  of  the  impulse  differs  even  in  perfectly 
normal  individuals,  owing  to  differences  in  the  thickness  of  the  chest 
wall. 

Under  ordinary  conditions,  the  cardiogram  consists  of  a  series  of 
upstrokes  and  downstrokes.  The  former  indicate  the  successive  sys- 
tolic and  the  latter  the  successive  diastolic  movements  of  the  ventricles. 
In  complete  agreement  with  the  general  character  of  the  contraction 
of  the  cardiac  muscle,  these  two  limbs  of  the  curve  are  generally  joined 


i'cc  I 


Fig.  144. — Cardiogram. 
AB,  Systole;BC,  plateau;  CD,  diastole;  DA,  pause;  time  in  seconds. 

by  a  "plateau,"  the  implication  being  that  this  muscle  does  not  relax 
immediately  upon  having  attained  its  state  of  maximal  shortening, 
but  remains  in  this  condition  for  a  brief  period  of  time.  The  curve 
may  also  present  an  initial  slight  rise  which  is  caused  by  the  systole  of 
the  auricles,  and  a  small  peak  upon  its  downstroke  which  occurs 
synchronously  with  the  closure  of  the  semilunar  valves.^ 

^  For  purposes  of  diagnosis,  it  is  necessary  to  ascertain  not  only  the  location 
of  the  impulse  but  also  its  strength.  A  displacement  of  it  is  brought  about  by 
accumulations  of  air  (pneumothorax),  serum  (hydrothorax),  blood,  and  pus,  as 
well  as  by  tumors  of  the  thoracic  and  abdominal  viscera.     Hypertrophy  and 


286  THE    MECHANICS    OF    THE    HEART 

B.  THE  ELECTRICAL  VARIATIONS 

The   Action   Current   of   the   Heart.     Electrocardiography. — The 

activity  of  any  form  of  living  substance  is  accompanied  Vjy  the  produc- 
tion of  electrical  energy.  We  have  found  this  to  be  true  in  striated 
as  well  as  in  smooth  muscle  tissue.  Cardiac  muscle  forms  no  exception 
to  this  rule,  because,  if  the  heart  of  a  frog  or  turtle  is  exposed  to  the 
view  and  the  nerve  of  a  gastrocnemius  preparation  is  placed  upon  it,  the 
muscle  is  seen  to  twitch  with  every  systole.  In  this  particular  case, 
the  heart  acts  as  a  battery,  and  generates  an  impulse  in  the  adjoining 
nerve  which  then  causes  the  muscle  to  contract.  The  electrical  current 
generated  by  the  beating  heart  may  be  registered  by  means  of  suitable 
instruments,  such  as  the  capillary  electrometer,  or  the  galvanometer. 
Thus,  if  the  two  terminals  of  the  former  are  placed  upon  the  active 
organ,  preferably  upon  its  base  and  apex,  the  meniscus  of  the  mercury 
in  the  capillary  tube  moves  first  in  one  direction  and  then  in  the  other 
in  synchronism  with  the  successive  periods  of  activity.  The  same 
result  may  be  obtained  with  the  help  of  the  galvanometer,  the  reflecting 
mirror  of  this  instrument  being  doubly  deviated  with  each  contraction. 
The  current  rendered  recognizable  by  this  means  is  known  as  the 
current  of  action  of  the  heart.  It  is  dependent  upon  the  fact  that  the 
active  portion  of  this  organ  is  electronegative  to  the  resting  portion. 
Inasmuch  as  the  cardiac  contractions  begin  at  the  base,  this  particular 
area  of  the  heart  is  of  a  lower  electrical  potential  than  its  still  inactive 
apical  portion.  A  moment  thereafter,  however,  conditions  are  re- 
versed. The  apical  region  now  having  been  activated,  exhibits  a 
galvanometric  negativity,  while  the  basal  zone  which  is  in  the  state 
of  rest  at  this  very  time,  becomes  electropositive.  In  perfect  analogy 
with  skeletal  muscle,  the  action  current  of  the  heart  exhibits  a  diphasic 
character.  This  is  indicated  very  clearly  by  the  deflections  of  the  in- 
dicator of  the  recording  instrument  which  occurs  first  in  one  direction 
and  then  in  the  other.  It  should  be  added,  however,  that  this  current  is 
somewhat  different  from  the  ordinary^  action  current  of  skeletal  muscle, 
its  peculiarities  being  no  doubt  attributable  to  the  much  greater  com- 
plexity of  the  cardiac  musculature.  These  electrical  changes  are 
developed  with  great  rapidity,  so  that  the  capillary  electrometer  and 
the  ordinary  type  of  galvanometer  are  not  sufficiently  motile  to  follow 
the  different  phases  of  this  wave  with  accuracy.  This  difficulty  has 
been  almost  entirely  overcome  by  the  very  sensitive  string  galvanom- 
eter, invented  by  Ader^  and  modified  by  Einthoven.^  The  indicator 
of  this  instrument  is  a  filament  of  quartz  or  platinum  covered  with  a 
thin  coating  of  silver  and  suspended  between  the  poles  of  a  powerful 

dilatation  of  any  part  of  the  heart  also  change  its  position.  The  strength  of  the 
apex  beat  is  indicative  of  the  condition  of  the  cardiac  musculature,  but  only 
when  the  factors  previously  enumerated  have  been  properly  controlled. 

*  Compt.  rend.,  Ac.  Sci.,  Paris,  cxxiv,  1897. 

*  Ann.  der  Physik,  xii,  1903,  and  Pfluger's  Archiv.,  cxxx,  1909,  287. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  287 


electromagnet.  The  deviations  which  the  string  of  this  instrument 
suffers  in  the  course  of  each  cardiac  cycle,  may  be  projected  and  photo- 
graphed upon  sensitive  paper  moved  with  jjroper  rapidity.  The 
record  so  obtained  is  known  as  the  electrocardiogram,  and  the  complex 
apparatus  necessary  to  take  these  tracings,  as  the  electrocardiograph. 
This  method  of  studying  the  character  of  the  cardiac  contractions 
has  attracted  much  attention  in  recent  years;  in  fact,  it  has  been  so 
highly  developed  that  it  may  be  employed  as  an  important  diagnostic 
aid  in  ascertaining  the  functional 
capacity  of  even  the  human  heart. 
While  the  currents  produced  by 
this  organ  are  of  very  moderate 
strength,  the  modern  type  of  elec- 
trocardiograph has  been  rendered 
sufficiently  sensitive  to  detect  them 
with  ease.  As  AValler^  has  shown 
years  ago,  it  is  quite  unnecessary 
to  expose  the  heart  to  the  view, 
because  the  current  generated  by  it 
can  be  led  off  to  the  galvanometer 
by  simpl}'  applj'ing  the  terminals  of 
this  instrument  to  the  integument. 
In  the  human  subject,  the  elec- 
trodes are  usually  connected  with 
the  body  in  three  ways,  designated 
as  leads,  namely: 


Lead  I. — Right  arm  and  left  arm. 
Lead  IL — Right  arm  and  left  leg. 
Lead  III. — ^Left  arm  and  left  leg. 


Fig.   145. — DisTRisrTioN   of  Potex- 

TL\L     DiFFEREXCXS     DuE    TO    ELECTRICAL 

Variatioxs    IX    THE     Beatixg     Heart. 
(Waller.) 

To  record  the  variations  any  of  the 
points  a  may  be  led  off,  together  with 
any  of  the  points  b. 


In  the  first  case  in  which  the  two 
hands  are  connected  with  the  poles 
of  the  string  galvanometer,  the 
right  one  may  be  regarded  as  the 

conductor  which  leads  off  from  the  base,  and  the  left  one,  as  the  con- 
ductor which  leads  off  from  the  apex  of  the  heart. 

Regarding  the  general  outline  of  the  normal  electrocardiogram  and 
the  causes  of  its  different  minor  phases,  some  uncertainty  still  prevails. 
Figure  146  represents  the  electrocardiogram  most  commonly  obtained 
from  normal  human  subjects.  It  is  readily  observed  in  the  curve  of 
Lead  I  that  each  cardiac  cycle  begins  with  a  sHght  wave  which  has  been 
designated  by  Einthoven  as  the  P-wave  (presystolic).  Subsequent 
to  this  point,  the  string  either  retains  its  position  of  zero  or  is  deviated 
somewhat  below  the  base  line.  This  primary  deflection  is  due  to  the 
contraction  of  the  auricles  and  is  spoken  of,  inclusive  of  the  presystoUc, 


1  Philos.  Transact.,  1889,  180. 


288 


THE    MECHANICS    OF    THE    HEART 


as  the  "auricular  complex  of  the  electrocardiogram."^  The  "ven- 
tricular complex"  of  the  curve  is  much  more  complex.  When  fully 
developed,  it  consists  of  a  deflection  below  the  abscissa,  called  the  Q- 
wave,  a  very  conspicuous  upward  deviation  or  7^ -wave,  a  second 
depression  or  S-wave,  and  a  broad  rounded  elevation  or  T-wave. 
The  largest  variation  at  R  consumes  0.02  to  0.04  sec.  and  the  one  at 
T,  0.1  sec.  The  total  time  of  this  complex  corresponds  approximately 
to  the  duration  of  the  ventricular  contraction,  which  has  been  proved 


5 


ojSei 


Fig.  146. — Electrocardiogram  Obtained  by  Photographing  the  Movements  of  the 
Thread  of  a  String-galvanometer. 
The  upper  figure  shows  the  photographed  curve  while  the  lower  one  is  a  diagram 
constructed  from  the  photograph  to  show  the  electrical  changes  occurring  during  a  single 
cardiac  cycle.  To  obtain  this  record  the  electrodes  were  connected  with  the  right  and 
left  hands.  Waves  with  the  apex  upward  indicate  that  the  base  of  the  heart  (or  the 
right  ventricle)  is  negative  to  the  apex  (or  left  ventricle).  Waves  with  the  apex  down- 
ward have  the  opposite  significance.  Wave  P  is  due  to  the  contraction  of  the  auricle. 
Waves  Q,  R,  S,  and  T  occur  during  the  systole  of  the  ventricle.  The  curve  seems  to 
show  that  the  contraction  in  the  ventricles  begins  first  toward  the  apex  (or  in  the  left 
ventricle),  since  the  negativity  first  appears  toward  that  side  (waveQ).      (Einthoven.) 

to  begin  very  shortly  after  the  onset  of  the  deflection  at  R  and  to  con- 
tinue to  about  the  end  of  the  T-wave. 

A  detailed  discussion  of  the  individual  variations  in  the  electro- 
cardiogram^ cannot  prove  of  much  value,  because  many  matters 
pertaining  to  it  must  first  be  thoroughly  investigated.  Its  complexity, 
however,  clearly  betrays  the  segmental  arrangement  of  the  cardiac 
musculature  as  well  as  the  wave-like  character  of  its  contraction.  It 
appears  that  the  excitation  wave,  on  being  distributed  to  the  different 
areas  of  the  heart,  gives  rise  to  a  muscular  activity  which  is  not  at  all 

^  Lewis,  Clinic.  Electrocardiography,  London,  1913. 

2  Einthoven,  Pfliiger's  Archiv,  cxlix,  1913,  65;  Meek  and  Eyster,  Am.  Jour,  of 
Physiol.,  XXX,  1912,  271;  James  and  Williams,  Am.  Jour,  of  the  Medical  Sciences, 
1910,  and  Kraus  and  Nicolai,  "Das  Electrocardiogram,"  Leipzig,  1910. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE     289 

simultaneous.  For  this  reason,  tho  difforont  zones  of  the  cardiac 
musculature  must  present  different  electrical  potentials  toward  one 
another.  As  far  as  the  significance  of  the  general  details  of  the  electro- 
cardiogram are  concerned,  it  might  be  mentioned  in  brief  that  an  auricu- 
lar complex  of  the  form  previously  described,  indicates  that  the  wave 
of  excitation  arises  in  its  proper  place  at  the  venous  vestibule  and  is 
propagated  in  normal  sequence  through  the  whole  of  the  auricular  tissue. 
As  far  as  the  ventricular  complex  is  concerned,  it  should  be  noted  that 
the  deviations  at  R  and  T  are  always  present  in  normal  records  and 
that  the  deflections  at  Q  and  S  differ  greatly  in  amplitude.  Their 
presence  signifies  that  the  auricular  impulse  has  traversed  the  auriculo- 
ventricular  bundle  and  its  ramifications  in  a  proper  manner  and 
direction.  Ago  usually  lessens  the  conspicuousness  of  the  T-wave,  while 
exercise  increases  it.  Curiously  enough,  the  electrocardiogram  secured 
from  the  hearts  of  the  lower  forms,  coincides  very  closely  with  that 
obtained  in  mammals. 

C.  THE  HEART  SOUNDS 

First,  Second  and  Third  Sounds. — All  contracting  muscle  tissue 
emits  a  sound,  which  is  caused  by  the  molecular  shifting  of  its  sub- 
stance and  the  displacement  of  its  fibers.  The  intensity  of  this  sound 
must  therefore  be  proportional  to  the  mass  of  the  tissue  involved  as 
well  as  to  its  power  of  contraction.  In  the  case  of  the  heart,  three 
additional  factors  must  be  taken  into  account,  namely  (a)  the  play  of 
the  fibrous  flaps  forming  the  valves,  (6)  the  friction  of  the  blood  upon 
the  endocardial  Hning  of  the  narrowed  orifices,  and  (c)  the  friction  of 
the  organ  as  a  whole  against  the  chest  wall  and  neighboring  viscera. 
Clearly,  therefore,  the  sounds  heard  in  the  region  of  an  active  heart 
may  be  said  to  be  of  intracardiac  and  extracardiac  origin.^  While 
both  types  deserve  recognition,  the  former  are  of  much  greater  physio- 
logical importance. 

If  the  unaided  ear  is  applied  to  the  surface  of  the  chest  in  the 
region  of  the  heart  and  preferably  over  its  apex,  two  very  distinct 
sounds  are  heard  during  each  cardiac  cycle  which  may  be  represented 
phonetically  by  the  syllables  "lubb-dup"  or  ta-ta.  The  first 
possesses  a  rather  low  pitch  and  is  fuller  and  longer  than  the  snappy 
and  sharp  second  sound.  They  may  be  rendered  more  audible  by 
means  of  resonators,  such  as  are  contained  in  some  of  the  monaural 
or  binaural  forms  of  stethoscopes.  But  if  an  instrument  of  this  kind 
is  employed,  a  certain  care  must  be  exercised,  because  diverse  errors  in 
auscultation  may  arise  in  consequence  of  poorly  fitting  ear  pieces,  or 
in  consequence  of  the  improper  application  of  the  bell-shaped  receptor 
to  the  thorax.^ 

'  Noises  are  frequently  heard  in  other  parts  of  the  vascular  system,  generally 
at  the  points  where  the  channels  deviate  from  their  former  course  or  are  con- 
stricted.    Venous  bruits  are  not  at  all  uncommon. 

2  The  cardiac  sounds  are  modified  in  their  intensity  by  any  factor  (respiratory 
movements,  pulmonary  infiltrations,  pericardial  effusions,  etc.)  producing  a  change 
19 


290  THE  MECHANICS  OF  THE  HEART 

The  cardiac  sounds  have  been  recognized  at  an  early  date.  Harvey, 
for  example,  states  that  the  delivery  of  a  quantity  of  blood  into  the 
arteries  produces  a  pulse  which  can  be  heard  within  the  chest,  but 
Laennec^  was  the  first  to  describe  the  character  of  the  sounds  and  to 
make  use  of  them  for  clinical  purposes.  Graphic  records  of  them  have 
been  obtained  by  Bonders  (1856),  Martin  (1888)  and  Hiirthle  (1892), 
but  the  first  really  satisfactory  method  of  registration  has  been  devised 
by  Einthoven  and  Geluk.^  The  sounds  transmitted  by  a  stethoscope 
were  caught  upon  a  microphone.  The  currents  were  then  led  off  to  a 
capillary  electrometer,  and  photographed  by  projecting  the  move- 
ments of  the  mercurial  column  of  this  instrument  upon  sensitive  paper 
moved  with  a  certain  velocity.  In  recent  years,  this  means  of  regis- 
tration has  been  displaced  by  the  string  galvanometer,  Frank' 
has  devised  an  instrument  without  a  microphone,  the  sounds  being 
transferred  directly  from  a  stethoscope  onto  a  membrane  carrying  a 
reflecting  mirror.  It  should  be  mentioned,  however,  that  the  records 
so  obtained  are  not  always  satisfactory,  because  they  really  represent 
a  combination  of  phonogram  and  cardiogram.  Under  ordinary  con- 
ditions, however,  it  is  not  difficult  to  differentiate  between  the  rapid 
oscillations  caused  by  the  cardiac  sounds,  and  the  slow  deflections 
produced  by  the  contraction  of  the  cardiac  musculature.  By  means 
of  the  method  described  previously,  Einthoven^  has  succeeded  in 
registering  a  third  heart  sound  which,  however,  cannot  usually  be 
heard  with  the  stethoscope. 

The  first  sound  occurs  during  ventricular  systole.  It  begins  with 
the  "setting"  of  the  ventricles  and  continues  until  the  highest  intra- 
ventricular pressure  has  been  produced.  This  point  coincides  with 
the  beginning  of  the  plateau,  when  the  semilunar  valves  are  forced 
open.  It  is  loud  at  first,  but  becomes  less  intense  toward  the  end 
of  the  ventricular  contraction.     It  lasts  0.07  to  0.10  sec. 

It  may  be  concluded  that  the  first  sound  of  the  heart  is  due  very 
largely  to  the  friction  noises  emitted  by  the  contracting  ventricular 
musculature,^  because: 

(a)  It  is  also  produced  by  the  exposed  and  bloodless  heart,  and  also  by  excised 
portions  of  the  ventricle  and  by  apex  preparations. 

(6)  The  sound  begins  before  the  closure  of  the  auriculoventricular  valves 
and  continues  practically  throughout  ventricular  systole  until  the  muscle  fibers 
have  attained  their  maximal  degree  of  shortening. 

in  the  tissue  situated  between  the  heart  and  the  chest  wall,  as  well  as  by  structural 
alterations  in  the  musculature  of  the  organ  itself  (hypertrophy  and  dilatation). 
Moreover,  when  one  or  several  of  the  valves  become  incompetent,  the  resulting 
murmurs  seriously  impair  the  normal  character  of  these  sounds. 

1  De  I'auscultation,  Paris,  1819. 

2  Pfliiger's  Archiv,  Ivii,  1894,  617. 

3  Kongr.  fiir  inn.  Med.,  Wiesbaden,  xxv,  1908;  also  see:  Weiss,  Das  Phono- 
scope, Med.  nat.  Arch.,  Berlin  and  Wien,  i,  1908. 

*  Pfliiger's  Archiv,  cxx,  1907,  31. 

^  C.  J.  B.  Williams,  Rep.  Brit.  Assoc,  for  the  Adv.  of  Science,  London,  1836. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  291 

(c)  The  auriculovcntriciilar  valve  flaps  may  Ix;  hookod  hack  without  markedly 
impairing  the  quality  ol'  tin-  sound. 

((/)  The  character  of  the  sound  is  decrescent. 

(e)  The  contracting  auricles  also  emit  a  sound  whicii,  however,  remains  below 
the  threshold  of  audibility,  owing  to  the  small  mass  of  tissue  involved. 

It  is  generally  conceded,  however,  that  the  first  sound  also  contains  a 
shght  valvular  element,  because  if  the  play  of  the  valve  flaps  is  re- 
stricted or  prevented,  it  displays  a  somewhat  different  character.  We 
loiow  that  the  ventricular  systole  insures  first  of  all  the  closure  of  the 
auriculoventricular  valves  (Fig.  147  a),  and  shortly  thereafter,  the  open- 
ing of  the  semilunar  valves  (6).  As  the  outward  movement  of  the  latter 
is  accomplished  practically  without  noise,  it  must  be  concluded  that 
the  modification  imparted  to  the  muscular  element  of  the  first  sound 
must  be  dependent  upon  the  initial  contact  and  the  subsequent  after- 
vibration  of  the  closed  mitral  and  tricuspid  valves. 


Fig.   147. — Schema  to  Show  the  Relationship  Between  the  Heart  Sounds  and 
THE  Curve  of  Intraventricular  Pressure. 
AB,  systole;  BC  plateau;  and  CD,  diastole;  a,  closure  of  auriculoventricular  valve; 
b,  opening  of  semilunar  valve;  c,   closure  of  semilunar  valve;  d,  opening  of  auriculo- 
ventricular valve;  /,  //  and  ///,  heart  sounds. 

The  second  sound  occurs  at  the  beginning  of  ventricular  diastole 
and  follows  immediately  upon  the  closure  of  the  semilunar  valves. 
It  lasts  0.05-0.11  sec,  while  the  interval  between  it  and  the  first 
sound  amounts  to  0.15-0.25  sec.  It  is  most  intense  when  the  blood 
pressure  is  high  and  when  the  arterial  system  is  very  elastic. 

In  contradistinction  to  the  first  sound,  the  second  sound  possesses 
no  muscular  element.  It  is  purely  valvular  in  its  origin  and  is  caused 
by  the  tension  and  after-vibration  of  the  closed  semilunar  valves. 
This  can  be  shown  in  the  following  way: 

(a)  If  the  tension  in  the  aorta  and  pulmonary  artery  is  lessened  by  permitting 
a  quick  escape  of  the  arterial  blood,  the  intensity  of  the  second  sound  is  greatly 
diminished. 

(6)  If  the  heart  is  rendered  bloodless,  it  ceases  to  give  a  clear  second  sound. 

(c)  If  the  semilunar  valve-flaps  are  hooked  back,  the  second  sound  gives  way 
to  a  murmur,  due  to  the  regurgitation  of  the  blood  into  the  ventricular  cavity. 

(d)  A  sound  very  similar  in  character  to  the  second  sound  may  be  produced  in 


292 


THE    MECHANICS    OF    THE    HEART 


an  excised  segment  of  aorta  by  quickly  forcing  a  column  of  water  through  the 
semilunar  orifice  toward  the  ventricular  cavity. 

The  third  sound  is  diastolic  in  its  nature  and  occurs  0.13  sec.  after 
the  beginning  of  the  second.  It  is  soft  and  low  in  pitch. .  Two  causes 
have  been  assigned  to  it.  As  it  appears  to  follow  in  the  wake  of  the 
second,  Einthovcn  has  suggested  that  it  is  dependent  upon  the  after- 
vibration  of  the  closed  semilunar  valves.  It  is  also  claimed  that  it 
is  due  to  the  vibration  of  the  auriculoventricular  valves^  which  are 
opened  at  this  moment  of  diastole,  and  to  the  friction-noises  occasioned 
by  the  blood  as  it  rushes  into  the  ventricles  {d). 


D.  THE  CHANGES  IN  INTRACARDIAC  PRESSURE 
The  Filling  of  the  Heart 

Methods  of  Registration. — By  the  term  intracardiac  pressure  is 
meant  the  pressure  to  which  the  blood  is  subjected  while  traversing 

the  different  chambers  of  the  heart. 
To  begin  with,  it  is  to  be  noted  that 
the  general  character  of  the  pressure 
variations  in  the  auricles  is  quite 
different  from  that  of  the  variations 
taking  place  in  the  ventricles,  but  that 
the  two  ante-chambers  as  well  as  the 
two  main  chambers  show  an  almost 
complete  correspondence.  In  addition 
it  should  be  remembered  that  the 
former  develop  equal  degrees  of  pres- 
sure, while  the  latter  do  not,  because 
the  pressure  encountered  in  the  left 
ventricle,  is  much  higher  than  that  pre- 
vailing in  the  right. 

The  methods  employed  to  determine 
the  intracardiac  pressures  may  be  ar- 
ranged in  two  groups,  the  first  em- 
bracing those  procedures  which  are 
practicable  only  when  the  heart  is  fully 
exposed  to  the  view,  and  the  second, 
those  which  are  also  practicable  when 
the  chest  is  still  closed.  In  the  first 
instance,  the  cardiac  chamber  is  con- 
nected directly  with  a  manometer.  En- 
trance to  the  auricular  cavity  is  effected 
through  its  appendage  into  which  a  cannula  may  be  inserted  without 
causing  the  slightest  disturbance  in  the  heart's  action.  The  right 
auricular  cavitj^  may  also  be  reached  by  introducing  a  hollow  probe 
through  the  superior  vena  cava,  and  the  left  cavity  by  introducing 
1  Thayer  and  Gibson,  Boston  Med.  and  Surg.  Jour.,  1908. 


Fig.  148. — Schema  to  Illus- 
trate THE  Method  of  Recordixg 
THE  Blood  Pressure  ix  the  Right 
Auricle  and  Vextricle. 

A  probe  (5)  filled  with  saline 
solution,  is  inserted  through  theext. 
jug.  vein.  The  tambour  (T)  regis- 
ters the  pressure  upon  a  kymograph 
{K).  The  connecting  tubing  is 
equipped  with  a  stop-cock  or  clip 
(C). 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  293 

a  tube  through  one  of  the  pulmonary  veins.  The  same  procedures  may- 
be followed  in  the  case  of  either  ventricle.  A  pointed  tube  attached 
to  a  manometer  is  forced  slantingly  through  its  wall.  This  method 
does  not  entail  a  loss  of  blood,  because  the  musculature  closes  firmly 
around  the  tube.  With  the  chest  closed,  the  right  auricle  and  ventricle 
may  be  explored  with  the  aid  of  a  long  catheter  which  is  introduced 
through  the  right  external  jugular  vein  (Fig.  148).  A  regurgitation  of 
the  blood  into  the  auricle  does  not  result  under  these  circumstances,  be- 
cause the  tricuspid  flaps  close  tightly  around  the  tube.  With  the  chest 
intact,  the  left  ventricle  may  be  rendered  accessible  to  the  recording 
instruments  by  means  of  a  slender  probe  which  is  inserted  through  the 
left  carotid  artery  and  the  aorta.  As  holds  true  in  the  case  of  the 
tricuspid  valve,  the  semilunar  flaps  attach  themselves  firmly  to  the 
tube  so  that  a  serious  regurgitation  cannot  result.  The  chest  remain- 
ing closed,  the  left  auricle  is  not  accessible  to  manometric  measure- 
ments, but  the  pulsations  of  its  wall  may  be  registered  by  means  of 
a  small  rubber  bulb  which  is  advanced  through  the  esophagus  until  it 
reaches  the  level  of  this  cavity. 

The  Mercury  Manometer. — The  determination  of  the  pressure 
developed  in  the  different  compartments  of  the  heart,  may  be  effected 
with  the  help  of  an  indicator  commonly  designated  as  a  manometer. 
This  instrument  has  been  developed  in  two  directions,  its  two  forms 
being  known  as  the  mercury  manometer  and  the  membrane  manometer. 
For  the  present  we  shall  confine  ourselves  to  a  consideration  of  the 
construction  and  method  of  application  of  the  former  instrument. 
In  its  earliest  form  it  consisted  of  a  perfectly  straight  tube  which  was 
filled  with  water,  the  pressure  being  indicated  by  the  height  of  the 
column  of  water.  Later  on  U-shaped  tubes  were  used  as  a  matter  of 
convenience.  A  still  more  practical  form  was  given  to  this  instrument 
in  1828  by  Poiseuille,  who  displaced  the  water  by  mercury.  As  the 
latter  possesses  a  specific  gravity  11.7  times  greater  than  that  of 
blood  and  13.55  times  greater  than  that  of  water,  the  hmbs  of  the  U- 
shaped  glass  tube  could  be  materially  shortened  without  diminishing 
the  range  of  this  instrument.  Another  important  modification  con- 
sisted in  filling  the  connecting  tube  between  the  manometer  and  the 
blood-vessel  with  an  anticoagulating  agent,  for  example,  with  a  concen- 
trated solution  of  sodium  bicarbonate  or  magnesium  sulphate.  But, 
when  testing  the  pressures  within  the  chambers  of  the  heart,  it  is  best 
to  use  normal  saline  solution,  because  the  leakage  of  even  an  inconsider- 
able quantity  of  the  aforesaid  fluids  into  the  circulation  is  prone  to 
produce  undesirable  results.  To  avoid  this  possibility  Marey  and 
Chaveau  employed  a  catheter,  the  free  end  of  which  was  closed  with 
a  delicate  rubber  membrane. 

The  displacement  of  the  column  of  mercury  in  the  U-shaped  tube  may  be  read 
off  directly  or  may  be  recorded  upon  the  paper  of  a  kymograph  in  the  manner 
described  by  Ludwig  (1847).  A  float  of  hard  rubber  is  placed  upon  the  mercury 
in  the  distal  hmb  of  the  manometer.     The  float  in  turn  is  equipped  with  a  vertical 


294 


THE    MECHANICS    OF    THE    HEART 


rod  which  carries  a  writing  outfit.  The  latter  consisted  originally  of  a  small 
capillary  glass  pen  which  was  connected  with  a  tiny  receptacle  filled  with  ink. 
The  record  was  made  upon  white  paper  revolved  with  a  certain  speed.  At  the 
present  time,  however,  smoked  paper  is  used  most  frequently,  the  writing  needle 
consisting  simply  of  a  delicate  crosspiece  situated  upon  the  free  end  of  the  vertical 
rod. 

One  difficulty  encountered  in  registering  changes  in  pressure  is  presented  by 
the  great  inertia  of  the  mercury.  In  the  heart,  the  fluctuations  are  extreme  and 
are  developed  with  such  rapidity  that  the  mercury  is  quite  unable  to  follow  them 
accurately.  To  begin  with,  its  sluggishness  causes  it  to  lag  behind,  while  when 
once  set  in  motion,  it  tends  to  continue  in  the  same  direction,  surpassing  the 
actual  pressure,  often  very  considerably.     For  this  reason,  it  is  practically  im- 


FiQ.   149. — Schema  to  Show  the  Connection  Made  Between  the  Artery  and 

Manometer. 

M,  manometer;  H,  mercurial  column;  F,  float;  D,  recording  needle;  K,  kymograph; 
B,  tube  leading  to  reservoir  filled  with  solution  of  sodium  carbonate;  R,  rubber  tubing 
filled  with  sodium  carbonate  solution;  C,  glass  cannula  in  artery;  A,  clip  upon  artery; 
V,  maximal-minimal  valve  (Frank)  to  be  inserted  in  this  circuit;  1,  maximal;  2,  minimal 
side;  Fi,  maximal  valve  of  Hiirthle.  A  minimal  valve  is  obtained  by  inverting  the 
central  tube. 

possible  to  obtain  an  exact  record  of  the  intracardiac  pressures  by  means  of  this 
instrument.  It  may  be  used,  however,  to  register  either  the  lowest  or  highest 
degrees  of  pressure,  as  well  as  the  mean  pressure.  To  accomplish  this  end,  a 
so-called  maximal-minimal  valve  must  be  interposed  between  the  heart  and  the 
manometer.^  In  its  simplest  form  this  valve  consists  of  a  short  cannula  which  is 
surrounded  by  a  wide  jacket  of  glass  (Fig.  14971).  The  free  end  of  the  cannula  is 
bevelled  and  is  equipped  with  a  flap  of  rubber  membrane  fastened  to  it  in  the 
manner  of  a  door.  As  the  different  waves  of  systolic  pressure  traverse  the  cannula 
this  flap  is  raised,  so  that  the  column  of  mercury  in  the  manometer  is  constantly 
forced  upward  until  it  accurately  counterbalances  the  pressure.     At  this  level  it  is 

1  Hurthle,  Pfliiger's  Archiv,  xliii,  1888,  399. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  295 

held,  because  a  movement  in  the  opposite  direction  is  prevented  by  the  immediate 
approximation  of  the  flap  to  the  mouth  of  the  cannula.  Quite  similarly,  the 
diastolic  minimum  may  be  determined  very  easily  by  inverting  the  glass  cannula 
so  that  its  outlet  is  now  directed  toward  the  heart.  The  mercury  is  then  drawn 
downward  until  it  approximates  the  lowest  pressure  prevailing  in  the  heart. 
The  mean  pressure  may  be  obtained  by  interposing  in  the  system  of  connecting 
tubes  a  stop-cock  which  is  closed  more  and  more  until  the  mercurial  column 
eventually  shows  only  the  smallest  possible  oscillations. 

As  the  pressure  in  the  auricles  is  low,  the  manometer  tube  should  be  filled 
with  water  instead  of  mercury.  The  displacement  of  the  water,  however,  should 
always  be  given  in  millimeters  of  mercury,  because  blood  pressures  in  general 
are  usually  adjusted  to  this  standard.  The  exact  height  of  the  pressure  registered 
by  the  manometer  at  any  one  moment  is  obtained  by  measuring  the  distance 
(H)  between  the  zero  line,  or  abscissa,  and  the  level  of  the  curve  recorded  by  the 
writing  needle  of  the  float.     This  distance  must  then  be  multiplied  by  two,  be- 


FiG.  150. — Diagram   to   Show   the   Adjustments   Necessary   for   Determining   the 
Zero-line  of  the  Manometer  (M). 
Its  central  limb  (A)  is  brought  upon  the  same  horizontal  line  as  the  level  of  the  water 
in  the  glass  bulb  (B)  when  held  at  the  level  of  the  blood  vessel  (C). 

cause  the  tube  is  U-shaped,  i.e.,  while  the  column  of  mercury  moves  upward  in 
its  distal  limb,  it  moves  downward  in  its  central  limb.  The  float,  of  course, 
indicates  solely  the  movement  of  the  distal  limb  of  the  mercury,  i.e.,  one-half  of 
the  total  movement  of  the  mercurial  column.  Another  factor  must  also  be  taken 
into'consideration,  namely  the  specific  gravity  of  the  fluid  against  which  the  blood 
pressure  is  exerted.  As  mercury  possesses  a  specific  gravity  which  is  13.5  times 
greater  than  that  of  blood,  the  height  of  the  column  of  mercury  {H)  must  be 
divided  by  13.5.  The  figure  so  obtained  must  then  be  subtracted  from  the  pre- 
ceding value.  The  complete  formula  for  calculating  the  blood  pressure  is  as 
follows : 

It  need  scarcely  be  mentioned  that  the  zero  line  must  be  accurately  determined 
beforehand  by  temporarily  connecting  the  manometer  with  a  glass  bulb  containing 
water.  When  the  level  of  the  water  is  approximated  to  that  of  the  mercury  in 
the  central  limb  of  the  instrument,  the  float  is  adjusted  at  zero.  The  blood- 
vessel in  which  the  pressure  is  to  be  ascertained,  must,  of  course,  be  approximated 
to  the  level  of  the  mercury  in  the  central  limb  of  the  manometer  (Fig.  150). 


296 


THE    MECHANICS    OF    THE    HEART 


Systolic,  Diastolic  and  Mean  Pressure. — The  pressure  in  the  cham- 
bers of  the  lieart  undergoes  extreme  variations  during  each  cardiac 
cycle.  The  lowest  values  are  reached  at  the  end  of  diastole  and 
the  highest  at  the  end  of  systole.  Thus,  the  pressure  in  the  left  ven- 
tricle rises  in  the  course  of  0.06  sec,  from  near  zero  to  about  130  mm. 
Hg.  The  former  is  called  the  diastolic  and  the  latter  the  systolic 
pressure.  For  ordinary  purposes  it  suffices  to  calculate  the  average 
pressure  by  simply  obtaining  the  arithmetical  mean  between  the 
diastoUc  and  systoUc  values.  It  is  essential,  however,  to  include  a 
considerable  number  of  cardiac  cycles  in  this  calculation. 

The  Membrane  Manometer. — The  tendency  has  been  in  recent 
years  to  procure  an  instrument  which  is  capable  of  following  the  rapid 
alterations  in  pressure  without  that  its  parts,  when  once  displaced, 
enter  into  vibrations  of  their  own.  It  is  desirable  at  all  times  to  obtain 
not  only  the  extreme  heights  of  the  pressure,  but  also  its  intermediate 
values;  in  other  words,  it  is  of  importance  to  secure  a  complete  trac- 


^S^viiiiiU'-N 


tn. 


i^k     T 


Fig.   151. — Diagram  of  Membrane  Manometer. 
M,  rubber  membrane  connected  with  writing  lever  (L).     The  drum  {T)  is  connected 
with  the  cannula  in  the  blood  vessel;  R,  rod  to  fa.sten  manometer  to  stand. 


ing  of  the  curve  of  pressure.  This  end  has  been  attained  with  a  fair 
degree  of  accuracy  by  means  of  elastic  manometers  in  which  the  pressure 
is  not  counterbalanced  by  the  weight  of  ordinary  liquids,  such  as  water 
and  mercury,  but  by  the  resistance  resident  in  an  elastic  body.  A 
rubber  disc  or  a  metal  spring  are  usually  employed  for  this  purpose. 

The  simple  membrane  manometer  designed  by  Hiirthle,!  consists  of  a  metal 
drum  closed  by  a  sheet  of  thin  rubber,  the  excursions  of  which  are  transferred 
directly  to  a  writing  lever  (Fig.  151).  The  sensitiveness  of  this  instrument  has  been 
much  increased  by  permitting  the  membrane  to  act  against  a  steel  spiral  which  in 
turn  is  connected  with  a  writing  lever.  This  principle  is  embodied  in  the  so-called 
spring,  torsion,  and  reflecting  or  optical  manometers.  In  all  of  them  the  variations 
in  the  pressure  of  the  blood  are  transmitted  through  the  column  of  the  fluid  con- 
tained in  the  connecting  tubes,  to  the  rubber  membrane  of  the  manometer.  The 
displacement  suffered  by  the  latter  in  consequence  of  the  transferred  pressure  is 
recorded  in  magnified  form  upon  the  paper  of  a  kymograph.  An  instrument  of 
this  kind  must  be  calibrated  repeatedly,  i.e.,  the  excursions  of  its  rubber  membrane, 
as  indicated  by  the  writing  lever,  must  be  compared  with  the  movements  of  a 
column  of  mercury  so  that  they  may  be  expressed  in  terms  of  millimeters  of 
mercury. 

^  Pfliiger's  Archiv,  xlix,  1891,  29.  The  first  elastic  manometer  was  constructed 
by  Fick  in  1864  in  compliance  with  the  metal  manometer  of  Bourdon. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE     297 

Tho  nianomctors  designed  by  O.  Frank'  do  not  diffor  materially  from  those 
devised  by  Hiirthle.  The  principle  involved  in  their  construction  is  that  the  mass 
of  li(iuid  actually  moved  for  the  purpose  of  transferring  the  blood  pressure,  must 
be  as  small  as  possible,  otherwise  the  momentum  of  the  different  parts  of  the  instru- 
ment may  give  rise  to  vibrations  which  are  not  at  all  in  keeping  with  the  conditions 
as  they  actually  are.  The  tendency  to  "after-vibrate, "  Frank  has  sought  to 
mitigate  by  making  the  connecting  tube  between  the  blood-vessel  and  the  man- 
ometer as  large  and  as  short  as  possible,  while  the  orifice  carrying  the  recording 
membrane  is  reduced  to  the  smallest  size  practicable  (Fig.  152).  The  frequency 
of  vibration  of  this  instrument  is  extremely  great  and  hence  its  power  of  accurately 
following  th(>  variations  in  pressure  cannot  be  doubted.  Without  desiring  to  enter 
into  a  detailed  discussion  of  the  theory  of  manometers,  it  may  be  stated  that 
Hiirthle  does  not  regard  the  principle  as  put  down  by  O.  Frank  as  physically 
sound.-  Naturally,  the  greatest  sensitiveness  is  attained  by  the  reflecting  or  optical 
manometer.  The  membrane  of  this  instrument  is  not  weighted  by  a  writing  lever 
with  its  different  adjustments,  but  is  equipped  solely  with  a  very  small  mirror 


Fig.  152. — Diagram  of  Frank's  Membrane  Manometer. 
K,   for  attachment  of    cannula  inserted  in   blood  vessel;   hde,   connecting  piece  of 
manometer  filled  with  sodium  carbonate  solution;  cf,  connections  for  flushing  out  the 
system;  S,   membrane;  S,   mirror  riding  upon   membrane. 

from  which  a  beam  of  light  is  reflected  against  a  screen.  In  this  way,  the  oscilla- 
tions of  the  membrane  may  also  be  transferred  upon  the  sensitive  paper  of  a  camera 
moved  with  a  certain  rapidity 

The  Intra-Auricular  Pressure  and  the  Function  of  the  Auricles. — 

If  the  cavity  of  the  right  auricle  of  a  dog  is  connected  with  a  maxi- 
mal-minimal valve  and  with  a  mercury  manometer,  it  will  be  found  to 
produce  a  systolic  pressure  of  about  20  mm.  Hg.  and  a  diastolic  pressure 
of  —10  to  —20  mm.  Hg.'  The  total  change  in  pressure  in  this  cham- 
ber, therefore,  amounts  to  30  or  40  mm.  Hg.  during  each  cardiac  cycle. 
Very  similar  conditions  prevail  in  the  left  auricle.  It  may  be  stated 
at  this  time  that  the  negative  pressure  encountered  in  these  cavities, 
as  well  as  in  the  central  venous  trunks,  is  not  developed  actively,  but 
is  dependent  upon  the  aspiratory  action  of  the  tissue  of  the  lungs. 
These  organs  exert  an  elastic  pull  upon  the  relatively  soft  walls  of  these 

1  Zeitschr.  fiir  Biologic,  1910,  53. 

^  Pfliiger's  Archiv,  cxxxvii,  1911,  225. 

3  Goltz  and  Gaule,  ibid.,  xvii,  1878,  100. 


298  THE  MECHANICS  OF  THE  HEART 

venous  compartments,  in  consequence  of  which  the  blood  within  them 
is  placed  under  a  lower  pressure  than  it  would  be  otherwise.  The 
veins  outside  the  thorax,  on  the  other  hand,  are  exposed  to  the  atmos- 
pheric pressure.  Obviously,  therefore,  this  negative  pressure  in  the 
central  part  of  the  circulatory  system  must  disappear  immediately 
upon  opening  the  chest,  because  the  ensuing  collapse  of  the  lungs 
nulUfies  their  elastic  pull  upon  the  blood-vessels.  The  opposite  effect 
may  be  produced  under  normal  conditions  by  raising  the  intrathoracic 
pressure,  as  may  be  done  by  holding  the  breath  or  by  making  forced 
expiratory  movements.  A  far-reaching  venous  engorgement  and 
arterial  deficiency  may  thus  be  incited,  which  are  indicated,  on  the  one 
hand,  by  the  swelhng  of  the  superficial  veins  and,  on  the  other,  by  the 
lessened  amplitude  of  the  arterial  pulse.  Obviously,  this  rise  in  the 
venous  pressure  must  be  associated  with  a  lessened  filHng  power  of 
the  auricles,  because  the  relaxation  of  these  parts  is  then  greatly 
hindered  by  the  pressure  resting  upon  their  outer  surfaces. 

If  a  continuous  record  is  made  of  the  changes  in  the  intra-auricular 
pressure  with  the  help  of  an  elastic  manometer,  the  curve  so  obtained 

ISqnii.       ^... 


Fig.   153. — The  Curve  of  Intra-auricular  Pressure. 
AB,  systole;  BD,  diastole;  DA,  pause;  C,  second  summit;  E,  third  summit. 

presents  the  details  indicated  in  Fig.  153.  The  systolic  period  of  the 
auricle  occurs  between  A  and  B,  and  the  diastolic  between  B  and  D. 
Between  this  point  and  the  beginning  of  the  next  cardiac  cycle  {DA)  the 
auricle  is  said  to  be  at  rest.  The  wave  as  a  whole  exhibits  three  eleva- 
tions, namely,  one  each  at  5,  C  and  D.  The  first,  no  doubt,  is  due  to  the 
contraction  of  the  auricle,  and  indicates  the  point  of  maximal  intra- 
auricular  pressure.  The  second  summit  (C),  interrupts  the  steady  fall 
in  pressure  accompanying  the  relaxation  of  the  auricular  muscula- 
ture (BD).  Its  cause  is  to  be  sought  in  the  slight  upward  displace- 
ment of  the  auriculoventricular  septum  occasioned  by  the  contraction 
of  the  ventricles.  The  size  of  the  auricular  cavity  is  somewhat  dimi- 
nished thereby,  causing  the  pressure  to  rise.  The  third  elevation  (E) 
is  dependent  upon  the  quick  inrush  of  venous  blood  which  results  as 
soon  as  the  auricular  wall  becomes  passive.  This  rather  abrupt  initial 
rise  soon  gives  way  to  a  more  gradual  one,  as  the  auricles  become  filled. 
The  auriculoventricular  valves  are  forced  open  at  E.  A  certain  quan- 
tity of  blood  then  escapes  into  the  now  diastoUc  ventricles.     This 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  299 

change  permits  of  an  equalization  of  the  pressures,  so  that  the  filling 
may  take  place  more  slowly.  This  period  is  indicated  in  the  dia- 
gram by  the  letters  E  and  A,  the  latter  marking  the  beginning  of  the 
subsequent  auricular  systole. 

As  the  orifices  of  the  venae  cavae  and  pulmonary  veins  are  not 
guarded  by  valves,  the  variations  in  intra-auricular  pressure  must 
necessarily  be  propagated  outward  into  the  adjoining  venous  trunks. 
They  appear  here  in  the  form  of  the  physiological  venous  pulse.* 
In  accordance  with  the  preceding  discussion,  it  must  also  be  evident 
that  an  incompetency  of  either  the  tricuspid  or  mitral  valve  must 
occasion  a  much  gi-eater  second  rise  in  the  intra-auricular  pressure  than 
is  present  under  normal  conditions.  This  must  be  so  because  the  auric- 
uloventricular  flaps  now  not  only  encroach  upon  the  space  of  the 
auricles,  but  permit  a  certain  quantity  of  ventricular  blood  to  escape 
into  these  cavities.  The  summit  at  C  is  then  rendered  more  conspicu- 
ous, until,  in  severe  types  of  insufficiencies  of  these  valves,  it  com- 
pletely obliterates  the  first  elevation  {A  to  B).  This  condition  gives 
rise  to  a  similar  modification  of  the  physiological  pulse  in  the  central 
veins,  the  second  elevation  increasing  in  size  until  it  becomes  almost 
confluent  with  the  first.  It  is  then  known  as  the  pathological  venous 
pulse. 

The  filling  of  the  auricles  is  accomplished  during  the  intervals  be- 
tween the  successive  rises  in  intra-auricular  pressure.  It  has  been 
shown  by  Burton-Opitz^  that  the  influx  of  blood  is  rapid  during  early 
diastole  (B  to  C),  but  is  much  diminished  during  the  rise  in  pressure 
occasioned  by  the  upward  bulging  of  the  auriculoventricular  septum 
(at  C).  Immediately  following  this  phase,  another  rapid  inrush  of 
blood  results  {C  to  D),  which,  as  has  been  stated  above,  is  responsible 
for  the  third  summit  upon  the  curve  of  intra-auricular  pressure.  Dur- 
ing the  subsequent  pause  (E  to  A),  the  flow  becomes  slower  and  slower 
until  it  again  ceases  during  the  next  systole  (A  to  B).  It  will  be  seen, 
therefore,  that  the  venous  blood  enters  the  auricles  at  a  time  when 
their  musculature  is  at  rest,  and  hence,  it  may  be  inferred  that  the 
influx  of  the  blood  into  the  auricles,  or  the  filling  of  the  heart,  is 
occasioned  passively  by  the  circumstance  that  the  pressure  prevaiHng 
in  the  central  veins,  is  higher  than  that  existing  in  the  diastolic  auricu- 
lar cavities. 

The  auricles  serve  as  storehouses  for  the  ventricles,  because  they 
hold  a  certain  quantity  of  blood  in  readiness  until  the  very  moment 
when  they  must  deliver  it  to  the  ventricles.  But  the  dynamical 
conditions  in  the  vascular  system  are  subject  to  considerable  variations, 
and  hence,  the  quantity  of  blood  which  must  be  accommodated  by 
them,  is  not  always  the  same.  Owing  to  their  very  distensible  append- 
ages, the  auricles  are  structurally  well  fitted  to  adjust  themselves  to 

^  A  more  detailed  discussion  of  the  venous  pulse  will  be  found  upon  page  388. 
2  Am.  Jour,  of  Physiol.,  vi,  1902,  435. 


300  THE  MECHANICS  OF  THE  HEART 

van'ing  quantities  of  blood.  The  ventricles,  on  the  other  hand,  are 
much  more  compact  and  cannot  be  made  to  yield  so  readily.  It  should 
also  be  emphasized  that  the  auricles  do  not  simply  store  the  blood  in 
a  passive  way,  but  also  develop  a  driving  force  sufficiently  high  to  fill 
the  ventricles  to  their  utmost  capacity.  The  pressure  values  cited 
previously,  however,  prove  that  the  power  developed  by  them  is 
relatively  sUght,  but  inasmuch  as  they  discharge  their  contents  into 
the  ventricles  at  a  time  when  the  latter  are  at  rest,  practically  no  re- 
sistance need  be  overcome  by  them.  We  have  seen  that  the  inflo\\-ing 
venous  blood  opens  the  auriculoventricular  valves  sometime  before 
the  systoUc  movement  of  the  auricles  actually  begins.  This  enables  a 
moderately  large  quantity  of  blood  to  escape  into  the  ventricles  even 
before  the  onset  of  the  next  auricular  systole.  Consequently,  all  the 
latter  needs  to  accompHsh  is  to  force  in  an  additional  amount  so  that 
the  ventricle  becomes  fully  distended.  Their  duty  is,  so  to  speak, 
to  ram  the  charge  home. 

The  Intraventricular  Pressure  and  the  Function  of  the  Ventricles. — 
The  determinations  with  the  maximal-minimal  manometer  have 
proved  that  the  pressure  in  the  ventricles  is  subject  to  much  greater 
variations  than  the  pressure  in  the  auricles.  In  the  second  place, 
it  has  been  found  that  by  far  the  greatest  power  is  developed  by  the 
left  ventricle,  which  fact  is  in  perfect  agreement  with  the  extraordinary 
thickness  of  its  walls.  Obviously,  an  unusually  high  driving  force 
is  necessaiy  to  propel  the  blood  through  the  channels  of  the  systemic 
circuit.  Thus,  while  the  systohc  pressure  in  the  left  ventricle  of  the 
himian  heart  amounts  to  about  12.5-140  mm.  Hg.,  the  right  ventricle 
develops  a  pressure  of  scarceh'  more  than  50  mm.  Hg.  Much  higher 
values,  however,  are  obtained  whenever  the  circulatory^  mechanism 
is  called  upon  to  perform  an  extra  amount  of  work.  For  example,  one 
of  the  most  efficient  means  of  raising  the  intraventricular  pressure, 
as  well  as  the  general  blood  pressure,  is  muscular  exercise. 

During  diastole,  the  pressure  falls  to  within  a  few  millimeters  of 
zero.  In  fact,  a  sHght  negative  pressure  has  been  encountered  at 
times  in  certain  hearts,  but  as  this  result  is  not  constant,  its  cause  must 
be  sought  in  certain  accidental  conditions,  rather  than  in  an  active 
relaxation  of  the  cardiac  musculature.  This  conclusion  finds  confirma- 
tion in  the  fact  that  an  elastic  recoil,  such  as  is  possessed  by  a  rubber- 
bulb,  has  not  been  observed  in  the  case  of  the  heart.  Moreover,  it 
has  been  shown  that  a  normally  beating  organ  is  unable  to  derive  its 
supply  of  blood  from  a  U-shaped  tube  adjusted  at  its  own  level. ^ 
In  addition.  Porter-  has  proved  that  the  negative  pressure  in  the 
ventricles  is  not  associated  with  a  corresponding  fall  in  the  intra- 
auricular  pressure,  and  hence,  it  may  be  inferred  that  the  venous 
column  without  is  not  subjected  to  an  actual  suction  action.  Several 
explanations  have  been  offered  for  this  occasional  negative  pressure. 

^  Von  den  Velden.  Zeitschr.  fiir  exp.  Path,  und  Ther.,  iii,  1906. 
-  Jour,  of  Physiol.,  xiii,  1892,  513. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  301 

Thus,  it  has  )3oen  suggested  that  the  sudden  cessation  of  the  ventricu- 
lar systole  forces  the  column  of  blood  onward  with  a  certain  momen- 
tum, while  in  the  wake  of  it  is  developed  an  area  of  very  low  pressure. 
The  second  and  more  probable  explanation  takes  into  account  the 
fact  that  the  sudden  discharge  of  the  ventricular  contents  gives  rise 
to  an  abrupt  distention  of  the  trunks  of  the  aorta  and  pulmonary  artery 
wliich  in  turn  leads  to  an  expansion  of  the  basal  portion  of  the  heart, 
inclusive  of  the  adjoining  extent  of  the  ventricle.  This  effect  is  espe- 
cially evident  in  the  left  cavity,  because  its  wall  is  more  compact  and 
relatively  unyielding.  In  an  experimental  way  this  condition  may  be 
imitated  by  suddenly  distending  the  roots  of  the  aorta  and  pulmonary 
artery  with  fluid,  while  the  intraventricular  pressure  is  being  registered 
by  a  mercury  manometer  which  is  connected  with  this  cavity  by  means 


Fig.   154. — The  Curve  of  Ixtravextricul.ui  Pressure. 
AB,  systole  of  ventricle;  BC,  plateau;  CD,  diastole;  DA,  pause. 

of  a  trocar  inserted  directly  through  its  wall.     Every  distention  then 
gives  rise  to  a  negative  pressure. 

The  systole  of  the  ventricle  is  indicated  in  Fig.  154  by  the  abrupt 
rise  occurring  between  A  and  B.  The  normallj^  beating  ventricle,  how- 
ever, does  not  relax  immediately  upon  the  completion  of  its  contrac- 
tion but  remains  in  this  condition  for  a  brief  period  of  time.  We 
observe,  therefore,  that  the  maximal  value  of  the  pressure  is  maintained 
and  that  the  summit  of  the  curve  is  flat.  The  "plateau"  so  formed^ 
is  indicated  in  the  figure  by  the  letters  B  and  C.  The  subsequent  re- 
laxation of  the  ventricles  occurring  between  C  and  D,  is  accompanied 
by  a  rapid  fall  in  pressure.  During  the  pause  the  pressure  rises  very 
slowly,  owing  to  the  gradual  influx  of  blood  through  the  just  barely 
opened  auriculoventricular  valves.  As  has  been  stated  above,  the 
ventricles  are  filled  for  the  most  part  before  the  succeeding  auricular 
contraction  actually  begins,  so  that  the  latter  merely  serves  the  purpose 
of  adding  a  certain  extra  amount  of  blood. 

^  The  claim  has  recently  been  made  by  Straub  that  the  summit  is  pointed ; 
Hiirthle,  however,  has  proved  this  view  to  be  erroneous. 


302  THE  MECHANICS  OF  THE  HEART 

Clearly,  the  function  of  the  ventricles  is  to  develop  the  pressure 
necessary  to  drive  the  blood  through  the  vascular  system.  They 
impart  kinetic  energy  to  the  blood,  and  naturally,  as  the  resistance 
in  the  general  circuit  is  much  greater  than  that  in  the  pulmonary  cir- 
cuit, the  left  ventricle  must  produce  a  much  higher  pressure  than  the 
right.  We  have  previously  seen  that  the  changes  in  intra-auricular 
pressure  are  propagated  outward  into  the  veins,  where  they  appear  in 
the  form  of  the  physiological  venous  pulse.  In  a  similar  manner,  the 
intraventricular  pressure  makes  itself  felt  throughout  the  arterial 
system,  where  it  forms  the  basis  of  the  arterial  pulse,  because  each 
ventricular  discharge  raises  the  pressure  in  these  channels  above  that 
prevailing  during  the  diastolic  period  of  the  heart.  This  topic  will 
be  dealt  with  in  greater  detail  in  a  subsequent  chapter. 

The  cardiac  output  per  unit  of  time  varies  directly  with  the  fre- 
quency of  the  contraction  and  the  power  of  filUng  of  the  ventricles. 
Approximate  values  may  be  obtained  in  several  ways,  namely  by: 

(a)  Calculation  from  the  total  amount  of  blood  present  in  the  body. 
(5)  Measuring  the  capacity  of  the  chambers  of  the  excised  heart. 

(c)  Determining  the  volume-curve  of  the  beating  heart  by  means  of  the  cardi- 
ometer. 

(d)  Calibrating  the  aortic  blood-stream  of  the  normal  or  excised  heart  with  the 
aid  of  a  stromuhr,  or  current  measurer. 

In  addition,  Zuntz  has  devised  an  indirect  method  for  determining 
this  factor  which  depends  upon  a  comparison  of  the  amounts  of  oxygen 
in  the  respiratory  air,  and  the  differences  in  the  oxygen  content  of  the 
arterial  and  venous  blood.  To  illustrate,  a  horse  weighing  360  kilos 
uses  2733  c.c.  of  oxygen  in  a  minute,  and  its  arterial  blood  contains 
10.33  per  cent,  more  oxygen  than  its  venous  blood.  Thus,  as  every 
100  c.c.  of  pulmonary  blood  are  charged  with  10.33  c.c.  of  oxygen,  and 
as  in  all  2733  c.c.  of  this  gas  are  consumed  in  a  minute,  the  total  quan- 
tity of  blood  traversing  the  lungs  must  amount  to : 

100  X  2733      _  .  __ 
"-10:33-  ^  '^'^^^  '•'' 

Assuming  a  cardiac  frequency  of  50  in  a  minute,  each  contraction  of  the 
right  ventricle  must  yield  about  50  c.c.  of  blood.  Moreover,  as  the 
left  ventricle  works  in  perfect  unison  with  the  right,  this  figure  must 
also  represent  the  aortic  discharge.  Plesch  states  that  the  cardiac 
output  amounts  to  59  c.c,  this  value  being  based  upon  gasometric 
experiments  upon  man.  By  using  the  absorption  of  nitrous  oxid 
gas  as  an  index,  Krogh^  has  found  values  ranging  between  40  and  120 
c.c.  in  accordance  with  the  frequency  of  the  heart.  This  author  also 
states  that  muscular  exercise  increases  the  output  very  markedly. 
By  following  a  similar  analytical  procedure,  Boothby^  has  obtained 
an  average  value  of  60  c.c. 

1  Skand.  Archiv  fiir  Physiol.,  xxvii,  1912. 

2  Am.  Jour,  of  Physiol.,  xxxvii,  1915,  383. 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE     303 

While  the  cUrect  determination  of  the  capacity  of  the  ventricles  of 
the  excised  heart  presents  no  unusual  difficulty,  it  cannot  possibly 
yield  exact  results,  owing  to  the  changes  in  the  tonus  and  elasticity 
of  the  musculature  subsequent  to  the  removal  of  the  organ  and  our 
inabihty  to  reproduce  the  rhythmic  changes  in  pressure  under  which 
the  heart  ordinarily  works.  The  attempt  has  also  been  made  to 
measure  the  cardiac  output  by  determining  the  difference  in  the  volume 
of  the  heart  during  its  systohc  and  diastoUc  periods.  Experiments 
of  this  kind  have  been  performed  by  Stefani,^  Knoll,-  Johannson  and 


Fig.   155. — Diagram  of  Roy's  Cardiometer. 


Tigerstedt,^  and  others.  They  consisted  in  inserting  a  cannula  into 
the  pericardial  sac,  and  in  registering  the  volumetric  changes  by 
means  of  a  suitable  piston-recorder.  But  naturally,  as  even  the 
slightest  increase  in  the  pressure  in  this  pouch  tends  to  hinder  the 
relaxation  of  the  heart,  the  resulting  values  cannot  be  said  to  be  exact. 
Moreover,  as  the  pericardial  membrane  also  envelops  the  auricles,  it 
cannot  be  avoided  that  the  volumetric  changes  of  this  portion  of  the 
heart  are  transferred  to  the  recorder  together  with  those  of  the  ven- 
tricles. Roy  and  Adami"*  have  employed  round  metal  capsules,  or 
cardiometers,  consisting  of  two  hemispherical  shells,  and  large  enough 
to  contain  the  heart  in  its  entirety.     The  space  intervening  between 

1  Archiv  de le  scienze  med.,  iii,  1879,  7,  and  Arch.  ital.  de  biol.,  xviii,  1892,  119. 

^  Sitzungsb.  der  Wiener  Akad.  d.  Wissensch.,  1881,  82. 

3  Skand.  Archiv  fur  Physiol.,  i,  1889,  345. 

*  British   Med.   Jour.,   ii,    1889,   and   Phil.   Transactions,    clxxxiii,  1892,  199. 


304 


THE    MECHANICS    OF    THE    HEART 


this  organ  and  the  metal  capsule,  was  filled  with  oil  and  was  connected 
with  a  piston-recorder  by  means  of  tubing.  Under  very  favorable 
conditions  the  excursions  of  this  instrument  should  correspond 
precisely  to  the  variations  in  the  volume  of  the  beating  heart.  This 
result,  however,  is  not  obtained  under  ordinary  circumstances,  because 
even  this  type  of  cardiometer  does  not  meet  all  the  requirements  of 
a  perfect  instrument  of  precision.  Johannson  and  Tigerstedt  have 
overcome  these  difficulties  in  a  measure  by  employing  a  bulbular  cap- 
sule just  large  enough  to  envelop  the  ventricular 
portion  of  the  heart.  The  round  opening  at  its 
upper  pole  is  closed  by  a  rubber  membrane  with 
a  central  perforation  through  which  the  ven- 
tricle is  inserted.  Henderson^  has  made  use  of 
hemispherical  capsules  of  glass,  and  of  ordinary 
rubber  balls  cut  in  half.  Great  care  must  be  ex- 
ercised that  the  opening  in  the  rubber  mem- 
brane is  not  too  small,  otherwise  the  filling  of 
the  ventricles  will  be  seriously  impaired.  Roth- 
berger,^  who  has  measured  the  ventricular  dis- 
charge directly,  finds  that  exact  values  cannot 
be  obtained  with  cardiometers  even  under  the 
most  favorable  conditions. 

The  attempt  has  been  made  by  Burton- 
Opitz^  to  calibrate  the  systolic  discharge  of  the 
right  ventricle  with  the  help  of  a  recording 
stromuhr,  or  current  measurer.  Piston  and 
syphon  recorders  have  been  employed  by 
Stolnikow^  and  Starling.^  The  systolic-diastolic 
changes  in  the  beating  heart  can  also  be  made 
out  very  clearly  during  transillumination  of  the 
chest  by  means  of  the  Rontgen  rays. 

It  may  be  said  in  a  general  way  that  a  rapid  heart  discharges  more 
blood  in  a  given  period  of  time  than  a  slow  one.  This  statement, 
however,  does  not  hold  true  under  all  conditions,  because  it  can  readily 
be  demonstrated  that  the  ventricular  output  may  vary  even  when  the 
cardiac  frequency  remains  the  same,  while,  at  another  time,  the  output 
may  remain  practically  unchanged  in  spite  of  the  fact  that  the  fre- 
quency of  the  heart  is  either  increased  or  decreased.  This  result 
indicates  that  the  cardiac  output  per  unit  of  time  is  dependent  not  only 
upon  the  number  of  systoles,  but  also  upon  the  quantity  of  blood  ejected 
each  time.  As  the  latter  factor  represents  the  filling  power  or  capa- 
ciousness of  the  heart,  it  must  be  evident  that  the  relaxability  of  the 

1  Am.  Jour,  of  Physiol,  xvi,  1906,  325. 
^Pfliiger's  Archiv,  118,  1907,  353. 

2  Proc.  Soc.  for  Exp.  Biology  and  Medicine,  1903. 
*  Archiv  fiir  Anat.  und  Physiol.,  1886,  i. 

5  Jour,  of  Physiol.,  xlv,  1912,  164. 


Fig.  156. — Cardio- 
meter. 
The  heart  is  inserted 
through  a  perforation  in 
rubber  membrane  (R) 
into  cavity  of  a  hemis- 
pherical gla.ss  capsule 
(C).  The  latter  is  con- 
nected with  a  recording 
tambour  (T). 


THE  PHENOMENA  NOTED  DURING  EACH  CARDIAC  CYCLE  305 

cardiac  musculature  is  of  as  great  importance  as  its  force  of  contrac- 
tion. Thus,  a  rai)itl  heart  may  ftiil  at  times  to  eject  a  hirger  quantity 
of  blood  than  a  slow  one,  because  the  length  of  time  allotted  to  it  for  its 
filling,  is  too  brief.  Quite  similarly,  a  slowly  beating  organ  may 
succeed  at  times  in  furnishing  a  perfectly  adequate  supply  of  blood, 
because  it  is  able  to  relax  more  fully  each  thne  and  to  take  in  a  corre- 
spondingly^ larger  amount 'of  blood.  Under  normal  conditions,  the  out- 
put of  the  left  ventricle  equals  that  of  the  right.  It  might  also  be 
mentioned  that  these  chambers  are  not  emptied  entirely  with  each 
systole,  but  that  a  small  amount  of  "residual"  blood  is  always  caught 
in  the  recesses  behind  the  different  valve  flaps. 

While  certain  unavoidable  difficulties  in  the  methods  make  it  im- 
possible to  present  exact  values  regarding  the  cardiac  output,  it  may  be 
concluded  that  the  average  ventricular  discharge  per  kilo  of  the  body 
weight  is  somewhat  greater  in  small  animals  than  in  large.  In  the 
dog,  for  example,  values  ranging  between  50  and  90  c.c.  have  been 
obtained.  The  ventricular  output  in  a  man  weighing  70  kilos,  has 
been  calculated  at  87  grams  with  a  cardiac  frequency  of  72  in  a  minute, 
but  this  value  is  probably  somewhat  too  high.  In  accordance  with 
the  total  quantity  of  blood  present  in  the  body,  it  has  been  calculated 
that  4.5  kilos  of  blood  are  propelled  during  72  cardiac  cycles  and  hence, 
62.5  grams  or  about  60  c.c.  of  blood  are  ejected  during  each  systole. 

The  Time  Relation  of  the  Cardiac  Cycle. — Each  cardiac  cycle 
begins  with  the  contraction  of  the  auricles,  these  chambers  being 
activated  at  practically  the  same  time.  It  will  be  remembered, 
however,  that  the  excitation-wave  begins  at  the  venous  vestibule  on 
the  right  side  and  hence,  it  has  been  possible  to  demonstrate  that  the 
left  auricle  lags  behind^the  right  by  a  fraction  of  a  second.  Fredericq,^ 
who  has  determined  this  interval  by  exact  graphic  measurements, 
states  that  its  duration  is  0.01-0.03  sec. 

The  systole  of  the  auricles  is  followed  after  an  interval  of  0.1  sec. 
by  that  of  the  ventricles.  Obviously,  this  time  is  required  for  the  pas- 
sage of  the  wave  of  excitation  through  the  bundle  of  His,  but  as  the 
stimulus  is  distributed  with  equal  rapidity  to  the  different  regions  of 
the  ventricles,  these  chambers  are  activated  at  practically  the  same 
time.  2  The  essential  fact  to  remember,  therefore,  is  that  the  auricular 
cycle  precedes  the  ventricular  by  about  0.1  sec.  and  hence,  the  ante- 
chambers complete  their  systole  before  the  contraction  of  the  main 
chambers  actually  begins. 

If  the  cardiac  rate  is  70  in  a  minute,  the  systole  of  the  auricles 
consumes  0.1-0.17  sec.  and  that  of  the  ventricles  0.37  sec.  Under  the 
same  conditions  the  diastole  of  the  former  occupies  0.76-0.69  sec, 
and  that  of  the  latter  0.48  sec.  Thus,  if  the  duration  of  each  cardiac 
cycle  is  taken  to  be  0.8  sec,  it  may  be  said  in  a  general  way  that  the 

1  Arch,  intern,  de  physioL,  1906,  57. 

2  Slight  dissociations  have  been  observed  at  times  in  disease,  due  probably 
to  effects  of  blocking  in  the  realm  of  the  ventricular  conducting  paths. 

20 


306 


THE    MECHANICS    OF    THE    HEART 


period  of  contraction  of  the  heart  lasts  0.4  sec,  and  that  of  relaxation 
and  rest  0.4  sec.^  Under  ordinary  conditions,  therefore,  this  organ 
rests  as  much  as  it  works.  Greater  frequencies  are  attained  at  the 
expense  of  the  pause  until  eventually  even  the  amplitude  of  the  con- 
traction is  lessened.  The  preceding  discussion,  however,  will  show 
that  a  frequency  of  120-140  per  minute  may  be  obtained  by  simply 
dropping  the  pause. 

E.  THE  PLAY  OF  THE  VALVES 

It  must  be  clearly  understood  at  this  time  that  the  movement  of 
the  valve  flaps  depends  upon  the  differences  in  pressure  to  which  their 


Fig.  157. — The  Intra\-entricular  (VP)  Pressure  in  Relation  With  the  Intra- 
AURicuLAR  Pressure  (AP)  and  the  Heart  Sounds  (<S). 
AB,  auricular  systole;  BD,  auricular  diastole;  DA,  auricular  pause;  BC,  ventricular 
systole;  CE,  ventricular  diastole;  EB,  ventricular  pause;  1,  closure  of  auriculo ventricu- 
lar valve;  2,  opening  of  semilunar  valve;  3,  closure  of  semilunar  valve;  4,  opening  of 
auriculoventricular  valve;  /,  //  and  ///,  first,  second  and  third  heart  sounds. 

upper  and  lower  surfaces  are  exposed.  To  begin  with,  the  blood  flows 
into  the  diastolic  auricles  until  it  finally  sets  up  a  pressure  which  is 
just  sufficient  to  push  the  auriculoventricular  valve  flaps  downward. 
A  part  of  the  auricular  contents  are  now  enabled  to  escape  into  the 
relaxed  ventricles.  The  mitral  and  tricuspid  valves,  therefore,  open 
sometime  before  the  onset  of  auricular  systole,  and  permit  the  ven- 
tricular cavities  to  become  partially  filled  even  before  the  auricles 
actually  begin  their  contraction  (Fig.  157).  Thus,  the  succeeding 
auricular  systole  {AB)  merely  serves  the  purpose  of  forcibly  filling  the 
ventricles  until  they  are  fully  distended.  Immediately  following  this 
phase,  the  auricles  relax  (BD),  while  the  ventricles  contract  {BC)  and 
develop  a  pressure  far  in  excess  of  that  prevailing  in  the  ante-chambers. 
The  auriculoventricular  valves  now  close  (1),  and  naturally,  their  closure 

1  More  specific  values  are  given  in  Tigerstedt's  Physiologic  d.  Kreislauf  es,  Leipzig, 
1893. 


THE    PHENOMENA    NOTED    DURING    EACH    CARDIAC    CYCLE      307 

must  be  effected  voiy  shortly  after  the  beginning  of  ventricular  sys- 
tole, i.e.,  at  the  moment  when  the  intraventricular  pressure  just  barely 
rises  above  the  intra-auricular.  A  fraction  of  a  second  later,  the 
swiftly  rising  pressure  opens  the  semilunar  valves  (2),  and  clearly,  the 
outward  displacement  of  these  flaps  must  occur  at  the  moment  when 
the  intraventricular  pressure  just  barely  overcomes  the  pressure  pre- 
vaihng  in  the  arteries.  As  is  indicated  in  the  accompanying  figure, 
the  opening  of  the  semilunar  valves  must  take  place  late  in  systole  at 
the  beginning  of  the  plateau.  As  soon  as  the  ventricular  musculature 
relaxes,  the  pressure  in  the  ventricles  falls  below  that  prevailing  in  the 
arterial  channels.  In  consequence  of  this  reversion  of  the  pressures, 
the  semilunar  valves  are  shut  under  the  weight  of  the  blood  as  it 
endeavors  to  seek  a  place  of  least  resistance  and  return  into  the  main 


Fig.   158. — Diagram  to  Illustrate  the  Position  of  the  Cardiac  Valves  During  {A) 

Auricular  Systole  and  (F)  Ventricular  Systole. 

Only  one-half  of  the  heart  is  represented. 

chambers  (3).  The  closure  of  the  semilunar  valves,  therefore,  is  effected 
immediately  after  the  beginning  of  ventricular  diastole,  i.e.,  as  soon  as 
the  intraventricular  pressure  falls  below  the  arterial.  Late  in  diastole, 
the  auriculovent  ricular  valves  again  open  and  permit  the  next  pre- 
systohc  filling  of  the  ventricles  (4). 

It  will  be  seen,  therefore,  that  the  ventricles  are  converted  into  com- 
pletely closed  cavities  twice  in  the  course  of  each  cardiac  cycle,  but  only 
for  the  briefest  possible  time  (Fig.  160).  This  must  be  so,  because  the 
semilunar  valves  cannot  open  until  the  main  chambers  have  been  com- 
pletely shut  off  against  the  auricles  by  the  closure  of  the  mitral  and 
tricuspid  valves  (1  to  2).  The'semilunar  valves  close  sometime  before 
the  mitral  and  tricuspid  valves  are  opened  by  the  inflowing  auricular 
blood  (3  to  4).  It  must  also  be  evident  that  the  ventricles  do  not 
eject  their  contents  into  the  arteries  as  soon  as  their  systolic  movement 
begins,  but  only  subsequent  to  the  moment  when  the  intraventricular 
pressure  exceeds  that  prevailing  in  the  arterial  trunks.  The  discharging 
period  of  these  cavities,  therefore,  begins  with  the  opening  of  the  semi- 


308 


THE    MECHANICS    OF    THE    HEART 


lunar  valves  and  continues  throughout  the  plateau  (2  to  3).  It  ceases 
with  the  beginning  of  diastole,  i.e..,  as  soon  as  the  semilunar  valves  are 
closed  by  the  high  outside  pressure.     The  early  phase  of  systole  during 


Fig.  159. — Schema  to  Show  Arrangement  of  Apparatus  for  Demonstrating  the 
Action  of  the  Heart  Valves. 
A,  reservoir  for  water;  H,  ox  heart;  B  and  C,  windows  inserted  in  the  orifices  of  the 
pulmonary  vein  and  aorta  overlying  the  mitral  and  aortic  valves;  E,  electric  battery 
and  light  used  to  illuminate  ventricular  cavity;  P,  pump  by  means  of  which  water  is 
made  to  circulate  and  to  close  and  open  the  valves. 

which  the  ventricles  simply  contract  upon  their  contents  without 
actually  ejecting  the  blood,  is  known  as  the  "setting  period."     Its  dura- 


FiG.  160. — Synchronous  Record  of  the   Intra venteiculab  Pressure   (V),  and  the 

Aortic  Pressure    (A) 
S,  the  time  record,  each   vibration  =    3'foo  sec;   0-5,  corresponding  ordinates  in 
the  two  curves;  1  marks  the  opening  of  the  semilunar  valves;  .3  (or  shortly  after)  marks 
the  closure  of  these  valves  and  the  beginning  of  diastole.     (Hilrthle.) 

tion  is  0.02-0.04  sec.  The  period  of  filling  of  the  ventricles  commences 
with  the  opening  of  the  auriculoventricular  valves  late  during 
diastole  and  ceases  with  the  beginning  of  the  next  auricular  systole. 


SECTION   VIII 
THE  NERVOUS  REGULATION  OF  THE  HEART 


CHAPTER  XXVII 
CARDIAC  INHIBITION  AND  ACCELERATION 

General  Discussion. — It  is  a  well-known  physiological  fact  that 
the  heart  continues  its  activity  not  only  after  it  has  been  isolated  from 
the  central  nervous  system  by  severing  all  its  nervous  connections, 
but  also  after  it  has  been  removed  from  the 
])ody.  The  excised  organ  of  the  lower  forms, 
for  example,  will  beat  rhythmically  for  hours 
and  even  for  days,  provided,  of  course,  that 
it  is  kept  under  proper  conditions  of  tempera- 
ture and  moisture,  and  is  supplied  with  a  nutri- 
tive fluid  of  some  kind.  Results  very  similar 
to  these  may  be  obtained  with  the  hearts  of 
mammals,  but  as  the  activity  of  these  organs 
is  more  closely  dependent  upon  an  adequate 
blood  supply,  they  must  be  handled  with  much 
greater  care.  These  experiments  show  very 
clearly  that  the  contractions  of  the  heart 
as  such  are  not  due  to  discharges  from  the 
central  nervous  system,  although  it  must  be 
admitted  that  a  proper  correlation  of  the 
function  of  this  organ  with  that  of  other  struc- 
tures cannot  be  achieved  unless  its  nervous 
connections  with  central  parts  have  been  pre- 
served. It  may  be  concluded,  therefore,  that 
the  inherent  power  of  the  heart  to  contract  is 
regulated  under  normal  conditions  by  a  ner- 
vous mechanism  consisting  of  a  center  and 
efferent  and  afferent  paths. 

The  Cardiac  Center. — The  nerve  cells  controlling  the  action  of  the 
heart,  are  situated  in  the  gray  matter  of  the  medulla  oblongata  below 
the  floor  of  the  fourth  ventricle  and  near  the  tip  of  the  calamus  scrip- 
torius.  This  center,  therefore,  lies  in  the  vicinity  of  the  respiratory 
and  vasomotor  centers,  but  its  exact  location  has  not  been  definitely 
ascertained  as  yet.     Suffice  to  say  that  this  part  of  the  central  nervous 

309 


-n.:-^'  I  I  it  Si 

Fig.  161.— The  Ner- 
vous Innervation  of  the 
Heart. 

CC,  cardiac  center;  M, 
motor  path  consisting  of 
cardio-inhibitor  and  car- 
dio-accelerator  fibers;  E, 
effector,  heart  muscle;  S, 
sensory  path  conveying 
impulses  from  different  re- 
ceptors (R),  such  as  the 
retina,  cutaneous  sense- 
organs,  etc. 


310  THE    NERVOUS    REGULATION    OF    THE    HEART 

system  gives  lodgment  to  a  certain  number  of  ganglion  cells  which 
give  origin  to  the  efferent  cardiac  fibers  and  serve  as  the  terminal 
station  for  a  number  of  afferent  channels.  It  should  also  be  mentioned 
that  this  center,  as  mapped  out  at  the  present  time,  possesses  solely  an 
inhibitor  function.  The  co-existence  in  this  region  of  an  accelerator 
zone  has  not  been  established  as  yet  but  may  be  surmised  upon  the 
basis  of  indirect  evidence.  Since  the  nervous  system  is  bilaterally 
arranged,  there  are  of  course  two  centers  and  two  sets  of  fibers,  one  on 
each  side  of  the  median  line  of  the  body. 

The  Efferent  or  Cardiomotor  Fibers. — These  fibers  are  inhibitor 
and  accelerator  in  their  function.  The  inhibitors  reach  the  heart  by 
way  of  the  vagus  or  pneumogastric  system,  and  the  latter  by  way  of 
the  cervical  spinal  cord  and  the  thoracic  sympathetic  gangha.  Both 
actions,  of  course,  are  autonomic,  i.e.,  they  are  not  under  the  direct 
control  of  the  will. 

The  inhibitor  fibers  were  discovered  in  1845  by  E.  H,  and  E. 
Weber.  ^  They  are  found  in  all  vertebrates  as  well  as  in  many  in- 
vertebrates. In  man,  their  presence  has  been  fully  established  by 
Czermak,2  Thanhoffer,^  and  others.  They  arise  in  the  nucleus  of  the 
vagus  and  follow  the  highway  of  this  nerve  to  the  heart.  Moreover, 
while  they  pursue  a  perfectly  independent  course  in  some  animals, 
such  as  the  woodchuck  (Simpson),  they  are  most  frequently  combined 
with  other  fibers  having  an  entirely  different  function.  The  cardiac 
branches  of  the  vagus  are  commonly  designated  as  the  superior  and 
inferior  cardiac  rami.  The  former  arise  from  the  cervical  portion 
of  the  vagus  somewhere  between  the  superior  and  inferior  laryngeal 
nerves,  while  the  latter  take  their  origin  from  the  thoracic  portion  of 
this  nerve  as  well  as  from  the  nervus  recurrens  directly.  Having 
attained  the  region  of  the  heart,  they  enter  into  relation  with  certain 
fibers  of  the  thoracic  sympathetic  system  (nervus  accelerans)  to  form 
the  plexus  cardiacus  which  envelops  the  ascending  portion  and  arch 
of  the  aorta.  From  here  they  are  distributed  to  the  nerve  centers 
(Remak's)  situated  in  the  domain  of  the  heart,  as  well  as  to  the  more 
distant  cardiac  musculature.  Those  fibers  which  connect  the  nucleus 
of  the  vagus  with  the  intracardiac  centers,  constitute  the  preganglionic 
path,  and  those  which  unite  the  intracardiac  plexus  with  the  muscle 
substance,  the  postganghonic  path. 

Division  of  the  vagi  nerves  has  been  practised  several  times  since  the  day  of 
Rufus,  Epheus  and  Galemis.  Willis  and  Lower  observed  toward  the  end  of  the 
seventeenth  century  that  this  procedure  leads  to  a  more  violent  pulsation  of  the 
heart,  this  result  being  attributed  to  a  weakness  of  the  heart.  In  1838,  Volk- 
mann  noted  that  an  inhibitor  effect  upon  the  heart  may  be  produced  by  stimula- 
tion of  the  vagus  nerve  with  a  constant  current.  Budge  employed  an  electro- 
magnetic rotation  apparatus  with  similar  results,  but  failed  to  give  an  adequate 
explanation  of  this  phenomenon. 

1  Handb.  der  Physiol.,  iii,  1846. 

2  Prager  Vierteljahrschr.,  1868,  100. 

3  Centralbl.  fiir  die  med.  Wissensch.,  1875. 


CARDIAC    INHIBITION    AND    ACCELERATION 


311 


The  existence  of  accelerator  fibers  has  been  estabhshed  experimen- 
tallj^  in  rabbits  by  von  Bezokl'  whose  results  have  been  substantiated 
for  warm-blooded  animals  by  M.  and  E.  Cyon,-  and  for  cold-blooded 
animals  by  Schmiedeberg.'  Although  it  cannot  be  definitely  stated 
that  these  fibers  arise  in  or  near  the  cardio-inhibitor  center  of  the 
medulla,  it  may  justly  be  assumed  that  they  possess  a  central  origin 


Fig.  162. — Schema.  Illustrating  the  DisTHiBtrTioN  of  the  Cahdiac  Nerves. 

MO,  medulla  oblcngata;  CC,  cardiac  center  (inhibitor  area  );  X,  nucleus  of  vagus 
nerve,  red  indicating  the  course  of  the  inhibitor  fibers;  SCR,  superior  cardiac  ramus; 
JCR,  inferior  cardiac  ramus;  V,  vagus;  SL,  superior  laryngeus ;  JL,  inferior  laryngeus; 
PC,  plexus  cardiacus,  and  preganglionic  path;  SC,  spinal  cord,  the  accelerator  fibers 
are  indicated  in  blue,  //,  ///,  and  IV  roots  of  corresponding  thoracic  spinal  nerves; 
S,  sympathetic  ganglion  along  spinal  cord;  SO,  stellate  ganglion;  AV,  annulus  of  Vieus- 
sens;  JC,  superior  cervical  ganglion  to  plexus  cardiacus  upon  arch  of  aorta. 

and  are  at  least  intimately  connected  with  this  area.  They  become 
clearly  recognizable  peripherally  in  the  anterior  roots  of  the  second, 
third  and  fourth  thoracic  spinal  nerves;  in  fact,  in  certain  animals  also 
in  the  lower  cervical  and  first  and  fifth  thoracic  nerves.  The  nerve 
cells  from  which  they  arise  are  situated  in  the  intermedio-lateral  tract 
of  the  spinal  cord.     For  this  reason,  they  may  be  regarded  as  forming 

^  Untersuch.  iiber  die  Innervation  des  Herzens,  ii,  1863. 

2  Centralbl.  flir  die  med.  Wissensch.,  1866. 

'  Ber.  der  sachs.  Gesellsch.  der  Wissensch.,  1870. 


312 


THE  NERVOUS  REGULATION  OF  THE  HEART 


a  spinal  cardio-accelcrator  center.  It  may  be  surmised  that  this  spinal 
center  is  controlled  in  turn  by  a  higher  center  located  in  the  medulla 
oblongata  near  the  cardio-inhibitor  center.  These  spinal  accelerator 
fibers  finally  reach  the  gangUon  stellatum  by  way  of  the  white  rami 
communicantes  (dog)  and  pass  by  way  of  the  annulus  of  Vioussens  to 
the  inferior  cervical  ganglion.  Their  terminals  are  to  be  found  in  these 
ganglia,  where  they  form  synapses  with  other  cells.  Fresh  relays  of 
non-medullated  fibers  continue  onward  through  the  cardiac  plexus  to 
the  musculature  of  the  heart.  The  latter  connection  seems  to  be 
effected  without  the  intervention  of  intracardiac  nerve  cells,  while  the 

inhibitor  fibers,  as  has  been  mentioned 
above,  are  intimately  associated  with 
Remak's  as  well  as  with  other  intrinsic 
ganglia  of  the  heart.  The  accelerator 
fibers  may  be  stimulated  at  almost  any 
point  of  their  course.  Very  favorable 
conditions  prevail  in  the  cat  in  which 
animal  a  distinct  nervus  accelerans  ex- 
tends between  the  stellate  ganglion  and 
the  cardiac  plexus. 

The  Character  of  the  Inhibition. — 
If  a  moderate  mechanical,  chemical,  or 
electrical  stimulus  is  applied  to  the  in- 
tact vagus,  the  normal  rhythm  of  the 
heart  soon  gives  way  to  a  much  slower 
one.  The  strength  of  the  stimulus 
may  then  be  increased  until  this  organ 
becomes  more  and  more  diastolic  and 
Fig.  163.-SKETCH  TO  Show  THE  Anally  ceases  its  activity  altogether. 
Accelerator  (and  Attgmentor)  A  functional  diminution  of  this  kind, 

Branches  from  the  Stellate  Gang-  qj,  inhibition,  as  it  Is  COmmonly  called, 
LION  (in  the  Cat,  Left  Side).  ,         ,  ^    .        ,  ,  ,    .        ,.,       ,  • 

,  ,,  ,    ,,        ,    r^u  may  be  obtamed  by  applymg  the  stimu- 

1,  the  ventral  branch  01  the  annu-  ''  .         "^^     ,  .   •'      '^         ■      e 

lus  (ansa  suhcla%4a) ;  2,  small  branch  luS  tO  any  pomt  Ot  thlS  nerve,  m  tact, 
not  constantly   present;   3,   Boehm's    even     tO     itS    nUclcuS    in     the    medulla. 

^^rZJSZ^-(^:l^'""  Under   ordinary    conditions,    however, 

its  cervical  portion  is  selected  for  the 
excitation,  because  it  is  more  accessible  than  its  cranial  or  thoracic 
portions.  It  should  also  be  remembered  that  the  inhibitor  mechan- 
ism is  not  equally  receptive  or  sensitive  in  all  animals,  and  secondly, 
that  the  inhibitor  power  of  the  right  and  left  vagi  differs  some- 
what even  in  the  same  animal.  Thus,  it  is  rather  difficult  to  cause 
a  complete  arrest  of  the  heart  of  the  cat,  while  it  is  comparatively 
simple  to  attain  this  result  in  the  dog.  Quite  similarly,  it  is  often 
impossible  to  cause  an  inhibition  with  the  aid  of  one  vagus,  while  the 
stimulation  of  the  opposite  nerve  gives  an  almost  immediate  maximal 
effect.  In  frogs,  turtles,  and  snakes,  the  right  nerve  is  generally 
the  stronger,   while  in  those  mammals  which  are  usually  used  for 


CARDIAC    INHIBITION    AND    ACCELERATION  313 

purposes  of  oxporimcntation,  oithor  the  i-isht  or  tho  loft  nerve  may  be 
the  inoi-e  effective.  As  the  inhibitor  impulses  pass  from  the  vagus 
center  to  the  periphery,  i.e.,  in  an  efferent  direction,  it  may  readily 
be  gathered  that  the  inhibition  may  also  be  obtained  by  stimulating 
solely  the  distal  end  of  the  divided  vagus.  In  the  frog,  turtle  and 
allied  animals,  it  is  also  possible  to  arrest  the  heart  by  applying  the 
electrodes  directly  to  its  sino-auricular  region,  because  this  particular 
area  gives  lodgment  to  a  plexus  which  possesses  an  inhibitor  function 
and  may  therefore  represent  the  principal  peripheral  relay  station 
of  the  vagus. 

The  inhibition  of  the  heart  is  characterized  by  a  gradual  pre- 
ponderance of  its  diastolic  period.  Its  systolic  movement  is  hindered 
more  and  more  until  its  musculature  temporarily  enters  a  state  of  com- 
plete   relaxation.     The  organ  as  a  whole  becomes  greatly  distended 


Fig.   164. — Record  of  the  Contractions  of  the  Frog's  Heart  During  Stimulation  of 

THE  Vagus  Nerve. 
The  time  is  given  in  seconds,  the  stimulation  is  indicated  by  the  signal. 

with  blood  and  exhibits  a  pronounced  venous  appearance.  The  in- 
hibition appears  as  a  rule  after  a  brief  latent  period  and  continues  for 
a  few  moments  after  the  cessation  of  the  excitation.  Furthermore, 
while  the  principal  effect  of  the  stimulation  consists  in  a  diminution  of 
the  frequency  of  the  heart,  this  inhibition  is  frequently  associated  with 
a  reduction  in  the  amphtude  of  the  individual  contractions.  Weak 
stimuli,  for  example,  are  prone  to  affect  solely  the  rate  and  to  give 
merely  a  partial  cessation  of  the  contractions,  while  stronger  stimuli 
diminish  the  height  as  well  as  the  frequency  of  the  contractions  until 
a  complete  stoppage  has  been  obtained.  The  strength  of  the  stimulus, 
however,  is  not  the  only  factor  determining  these  effects;  in  fact, 
we  shall  see  later  on  that  they  find  their  origin  in  certain  functional 
peculiarities  of  the  inhibitor  mechanism. 

The  inhibited  heart  resumes  its  activity  by  giving  a  contraction 
which  is  either  smaller  or  much  larger  than  normal.  In  either  case, 
the  beats  regain  their  former  amplitude  gradually  within  a  few 
nwments.  It  is  to  be  noted,  however,  that  the  heart  cannot  be 
kept  in  the  inhibited  state  for  any  length  of  time,  because  it  resumes 


314 


THE  NERVOUS  REGULATION  OF  THE  HEART 


its  beat  automatically  whenever  the  stimulation  is  unduly  prolonged. 
It  seems,  therefore,  that  the  excitation  eventually  induces  a  fatigue  of 
the  inhibitor  mechanism  which  permits  the  accelerator  influences  to 
gain  the  upper  hand.  This  "escape"  of  the  organ  from  the  power  of 
the  vagus  is  generally  confined  to  its  ventricular  portion,  the  auricles 
remaining  in  the  state  of  diastole.  No  definite  statement  can  be  made 
regarding  the  length  of  time  during  which  it  is  possible  to  maintain 
the  inhibition.  In  warm-blooded  animals,  the  "inner  stimulus"  most 
generaUy  makes  itself  felt  in  the  course  of  a  few  seconds,  while  in 

cold-blooded  animals  it  does  not 
exert  itself  until  after  several  min- 
utes. To  begin  with,  the  heart 
gives  a  few  isolated  beats,  and  then 
gradually  more  until  the  normal 
rhythm  has  again  been  established. 
The  inhibition  is  frequently 
followed  by  an  augmentor  effect 
which  is  characterized  by  an  in- 
creased frequency,  or  strength  of 
contraction,  or  both.  This  second- 
ary augmentation  is  especially  well 
shown  in  the  frog,  in  which  animal 
the  vagal  and  sympathetic  fibers 
are  united  into  a  common  nerve  at 
some  distance  from  the  heart.  For 
this  reason,  the  inhibitor  as  well 
as  the  augmentor  fibers  are  affected 
whenever  the  trunk  of  the  vagus 
is  stimulated.  Their  combined  ex- 
citation, however,  gives  rise  to  an 
inhibition.  If  it  is  desired  to  stimu- 
late the  inhibitor  fibers  separately, 
the  electrodes  must  be  applied  to 
them  as  they  emerge  from  the  vagal  foramen  and  before  they  have 
joined  the  sympathetic  fibers.  In  explaining  the  fact  that  the  ex- 
citation of  the  combined  vagosympathetic  fibers  always  leads  to  an 
inhibition,  it  must  be  remembered  that  the  augmentation  requires 
stronger  stimuh,  possibly  because  the  inhibitor  mechanism  is  more 
sensitive,  or  because  the  latent  period  of  the  augmentors  is  longer 
than  that  of  the  inhibitors.  Moreover,  even  if  these  impulses  are 
generated  at  precisely  the  same  moment,  as  they  probably  are 
when  the  vagus  itself  is  stimulated,  they  cannot  be  pitted  against 
one  another,  because  the  augmentor  influence  cannot  be  made  to 
antagonize  the  inhibitor.  Neither  can  the  latter  be  made  to  counter- 
act the  former.  It  seems,  therefore,  that  each  impulse,  when  once 
started,  must  run  its  course  until  the  reaction  to  which  it  contributes 
has  been  fully  completed.     Thus,  as  the  inhibitor  effect  is  produced 


Fig.   165. — Course  of  Vagus  Nerve  in 
Frog.     {Stirling.) 

SM,  submentalis;  LU,  lung;  V,  vagus; 
GP,  glosso-pharyngeal ;  HS,  hypoglossal; 
L,  laryngeal;  PH,  SH,  GH,  OH,  petro-, 
sterno-,  genio-,  and  omohyoid;  HG,  hypo- 
glossus;  H,  heart;  BR,  brachial  plexus. 


CARDIAC    INHIBITION    AND    ACCELERATION  315 

more  easily,  the  aiigmentor  effect  cannot  develop  until  the  inhibition 
has  been  brought  to  a  close,  or  has  lost  its  initial  power.  In  mammals, 
such  as  the  dog,  cat,  and  rabbit,  the  effects  of  the  stimulation  of  the 
vagus  are  very  similar  to  those  noted  in  the  frog  and  turtle,  with  this 
exception,  however,  that  the  secondary  augmentation  is  less  pro- 
nounced. It  also  seems  that  in  these  animals  the  augmentor  and 
the  inhibitor  fibers  antagonize  one  another  in  a  direct  manner,  because 
the  excitation  of  the  former  tends  to  lessen  the  action  of  the  latter. 

The  Nature  of  the  Inhibition. — Before  entering  upon  a  discussion 
of  this  topic,  brief  reference  should  be  made  to  the  question  of  whether 
the  vagal  impulses  are  distributed  solely  to  the  auricles  or  to  the 
ventricles,  or  to  both  parts.  Thus,  it  may  be  held,  on  the  one  hand,  that 
their  influence  is  apportioned  equally  to  all  parts  of  the  organ 
and,  on  the  other,  that  it  is  distributed  solely  to  the  auricle  and  par- 
ticularly to  the  area  of  the  "pace-maker."  In  the  first  instance, 
therefore,  the  cardiac  musculature  would  be  affected  directly  and,  in 
the  second,  solely  through  the  intervention  of  the  sino-auricular  node. 
The  latter  view  necessitates  the  assumption  that  the  ventricle  is  ren- 
dered inactive  on  account  of  the  failure  of  the  "pace-maker"  to  dis- 
charge those  waves  of  excitation  which  ordinarily  give  rise  to  its 
activity.  Gaskell  has  submitted  certain  evidence  to  show  that  in 
the  terrapin  the  inhibitor  impulses  are  received  by  the  auricle,  and  that 
the  ventricle  ceases  to  beat  because  no  stimuli  are  apportioned  to  it 
by  the  "pace-maker."  In  the  frog,  on  the  other  hand,  the  ventricle 
is  under  the  direct  control  of  the  vagus,  quite  independently  of  the 
auricles,  A  similar  relationship  seems  to  exist  in  the  mammals, 
the  vagus  fibers  being  distributed  to  the  auricles  as  well  as  to  the  ven- 
tricles. ^  This  is  shown  by  the  fact  that  the  contractions  of  the  auricular 
and  ventricular  musculature  may  be  dissociated  and  even  reversed. 

The  vagal  impulses  produce  their  characteristic  effect  either  by 
causing  the  musculature  to  relax,  or  by  diminishing  the  power  of 
conduction  of  the  bundle  of  His  and  its  ramifications.  On  the  whole, 
however,  the  experimental  evidence  favors  the  view  that  the  vagus 
exerts  its  action  primarily  through  the  auricles  and  the  "pace-maker" 
and  that  its  direct  action  upon  the  ventricles  is  slight  and  is  made  use 
of  only  under  singular  circumstances.  Engelman^  classifies  the  cardio- 
motor  impulses  as  follows: 

(a)  Chronotropic,  affecting  the  rate  of  the  contractions. 
(6)  Inotropic,  affecting  tlie  force  of  the  contractions. 

(c)  Bathmotropic,  affecting  the  irritability  of  the  muscular  tissue,  and 

(d)  Dromotropic,  affecting  the  conductivity  of  the  tissue. 

Every  one  of  these  influences  is  said  to  be  either  of  a  positive  or 
negative  kind.  The  former  result  in  consequence  of  the  excitation 
of  the  accelerator,  and  the  latter  in  consequence  of  the  stimulation  of 

1  Tigerstedt  (Lehrb.  der  Physiol,  des  Kreisl.,  Leipzig,  1893),  Frank  (Arch. 
der  Physiol.,  1891),  and  McWilliams  (Jour,  of  Physiol.,  ix,  1888). 

2  Arch,  fiir  Physiol.,  1900  and  1902. 


316 


THE  NERVOUS  REGULATION  OF  THE  HEART 


the  inhibitor  mechanism.  In  addition,  these  reactions  are  beheved 
to  be  brought  about  with  the  aid  of  four  different  sets  of  nerve  fibers. 
In  the  hght  of  the  preceding  discussion,  however,  it  would  seem  that 
these  different  pecuharities  of  the  heart  beat  should  rather  be  ascribed 
to  certain  differences  in  the  manner  of  distribution  of  these  impulses 
to  the  cardiac  musculature. 

Another  question  to  be  considered  at  this  time,  pertains  to  the 
specificity  of  the  vagus  nerve.  It  has  been  stated  above  that  the  cardio- 
inhibitor  effect  can  only  be  induced  with  the  help  of  this  particular 
nerve,  because  it  forms  the  sole  connection  between  the  central 
nervous  system  and  the  inhibitor  end-organs  in  the  heart.  It  ie, 
however,  a  well-known  physiological  fact  that  the 
character  of  a  reaction  does  not  depend  upon  the 
nerve  as  such,  but  upon  the  structural  and  func- 
tional peculiarities  of  the  end-organ  with  which 
it  is  connected.  The  vagus  nerve  does  not  form  an 
exception  to  this  rule,  and  hence,  it  must  be  con- 
cluded that  its  function  is  to  conduct  impulses, 
\  Ifl  /is  '  while  the  inhibition  depends  upon  certain  pecu- 
w7)  '▼'  AA^  harities  of  the  cardiac  effectors.  For  this  reason, 
the  cause  of  the  inhibition  of  the  heart  must  be 
sought  at  the  periphery,  namely,  in  certain  phj'sico- 
chemioal  alterations  in  the  vagal  terminals  and 
neighboring  muscle  cells.  The  specificity  of  the 
vagus,  therefore,  is,  so  to  speak,  "accidental." 
In  substantiation  of  this  statement,  it  might  be 
mentioned  that  it  is  possible  to  establish  a  func- 
tional union  between  the  central  end  of  the  divided 
fifth  cervical  nerve  and  the  distal  stump  of  the 
vagus.  Peculiarly  enough,  the  excitation  of  this 
formerly  musculo-motor  nerve  invariably  leads  to 
an  inhibition  of  the  heart.  In  a  similar  way,  this 
organ  could  be  inhibited  with  the  help  of  any  other 
efferent  nerve,  but  only  in  case  a  crossing  of  its 
fibers  with  those  of  the  vagus  is  an  experimental 
possibility. 
The  preceding  statements  regarding  the  specificity  of  the  vagus 
find  substantiation  in  the  changes  which  the  inhibitor  reaction  suffers 
in  consequence  of  the  administration  of  certain  drugs,  such  as  nicotin, 
atropin  and  muscarin.  To  illustrate,  if  the  heart  of  a  frog  or  turtle 
is  moistened  with  a  weak  solution  of  nicotin,  the  stimulation  of  the 
vagus  {V)  becomes  ineffective  as  soon  as  this  agent  has  had  sufficient 
time  to  penetrate  the  cardiac  tissues.  At  this  time,  however,  the 
excitation  of  the  plexus  at  the  sino-auricular  junction  (SAP)  of  the 
heart  still  gives  rise  to  an  inhibition.  Nicotin  is  a  cell  poison;  its 
action  being  centered  upon  the  dendritic  filaments  of  the  neurone. 
It  may  be  concluded,  therefore,  that  it  breaks  the  connection  between 


Fig.  166. — Schema 
TO  Illustrate  the 
Action  of  Nicotin. 

V,  vagus,  pregang- 
lionic path;  SAP, 
sino-auricular  plexus; 
P,  postganglionic 
pa th  ;  N,  nicotin 
breaks  connection  be- 
tween vagal  terminals 
and  postganglionic 
cell. 


CARDIAC    INHIBITION    AND    ACCELERATION 


317 


the  terminals  of  the  vagus  and  the  cells  of  the  intracardiac  plexus 
(Remak's)  which  innervate  the  peripheral  inhibitor  mechanism. 
Consequently,  the  stimulation  of  the  preganglionic  path,  constituted 
by  the  vagus  nerve,  must  remain  without  effect,  while  the  excitation 
of  the  postganglionic  path,  formed  by  the  cells  of  the  aforesaid  ganglion 
and  their  distal  axons,  must  give  rise  to  an  inhibition. 

If  atropin  is  applied  to  the  heart,  or  is  administered  in  a  general 
way,  negative  results  are  obtained  on  excitation  of  the  vagus  (V), 
as  well  as  on  excitation  of  the  sino-auricular  plexus  (SAP).  By  infer- 
ence, therefore,  it  may  be  concluded  that  this  alkaloid  produces  a  break 
in  the  conducting  path  peripherally  to  this  intracardiac  ganglion,  so 
that  the  cardio-inhibitor  impulses  are  no  longer  able  to  reach  the  end- 


f    (SAP 


Fig.  167.  Fig.   168. 

Fig.  167. — Schema  to  Illustrate  the  Actiox  of  Atropin. 

V,  vagus,  preganglionic  path;  SAP,  sino-auricular  plexus;  P,  postganglionic  path; 
A,  atropin  breaks  theconnection  between  thepostganglionic  pathandthecardiac  muscle. 

Fig.  168. — Schesla.  to  Illustrate  the  Action  of  Muscarin. 

V,  vagus,  preganglionic  path;  SAP,  sino-auricular  plexus;  P,  postganglionic  path; 
M,  muscarin  breaks  the  connection  at  the  neural  junction  or  paralyzes  the  musculature 
itself. 

organ.  The  cardio-accelerator  influences,  on  the  other  hand,  are  not 
blocked  and  hence,  we  observe  at  this  time  a  marked  increase  in  the 
frequency  of  the  heart.  Atropin  is  a  fiber  poison  and  paralyzes  the 
postganglionic  terminals.  In  time  to  come,  this  agent  is  oxidized  or 
is  excreted  in  its  original  form.  As  its  action  wears  off,  conduction  is 
gradually  restored  so  that  the  stimulations  of  the  vagus  and  of  the 
intracardiac  ganglion  again  become  effective. 

Pilocarpin  and  muscarin,  whether  applied  directly  to  the  heart  or 
administered  internally,  diminish  the  frequency  and  amplitude  of  the 
contractions  and  finally  produce  a  diastolic  stoppage.  Two  views 
are  held  regarding  the  action  of  these  drugs.  It  is  believed,  on  the 
one  hand,  that  they  paralyze  the  cardiac  muscle  tissue  directly,  and, 
on  the  other,  that  they  increase  the  irritability  of  the  nerve-tissue 
in  such  a  degree  that   the   inhibitor  mechanism  is  under  constant 


318       THE  NERVOUS  REGULATION  OF  THE  HEART 

excitation.  The  second  explanation,  proposing  that  the  inhibition  is 
due  to  a  stimialation  of  this  mechanism,  has  met  with  greater  favor, 
probabh'  because  it  can  be  brought  into  closer  relation  with  the  \4ew 
regarding  the  action  of  atropin,  which  agent,  in  contradistinction  to 
muscarin,  depresses  the  inhibitor  mechanism  by  lessening  the  irrir 
tabihtj'  of  the  postganglionic  fibers  and  their  ramifications.  This  ex- 
planation is  made  use  of  in  accounting  for  the  fact  that  the  inhibition 
established  by  pilocarpin  or  muscarin  may  be  removed  later  on  by  the 
administration  of  atropin.  It  must  be  evident,  therefore,  that  this 
agent  possesses  the  power  of  neutralizing  the  action  of  muscarin  so  that 
the  normal  rhythm  may  again  be  restored.  In  accordance  with  this 
view,  it  is  beheved  that  the  antagonistic  action  of  the  drugs  just 
mentioned  depends  upon  the  fact  that  the  atropin  causes  the  irri- 
tabilit}^  of  the  inliibitor  end-organs  to  be  gradually  diminished. 

It  must  be  acknowledged,  however,  that  the  first  view,  express- 
ing the  idea  that  muscarin  and  atropin  affect  the  cardiac  musculature 
directly,  is  not  without  foundation.  Thus,  it  has  been  shown  that 
these  drugs  give  rise  to  the  aforesaid  functional  changes  even  in  the 
hearts  of  mammahan  embrj^os  at  a  time  when  nervous  structures 
have  not  made  their  appearance  as  yet,  or  at  least,  long  before  the 
nervous  connections  have  been  fully  formed.  Besides,  it  has  been 
established  that  muscarin  does  not  affect  the  hearts  of  many  verte- 
brates.^ This  evidence,  however,  maj'  be  met  with  the  objection 
that  the  properties  of  the  fulh'  developed  organ  cannot  justly  be  com- 
pared with  those  of  the  embryonic  organ,  and  secondly,  that  the  ac- 
tion of  these  alkaloids  need  not  be  the  same  in  all  animals. 

Some  interesting  data  regarding  the  distribution  of  the  cardiac 
impulses  may  also  be  gathered  from  a  number  of  phenomena  which 
have  been  described  by  Stannius.  If  a  thread  is  tied  rather  loosely 
around  the  heart  of  a  frog  or  turtle  at  the  sino-auricular  junction, 
the  sinus  continues  to  beat  rhj'thmically,  while  the  remaining  portion 
of  the  heart  ceases  its  activity.  This  result  is  explicable  upon  the 
basis  that  the  wave  of  excitation  is  blocked  at  the  seat  of  the  hgature, 
but  it  is  also  possible  that  the  latter  serves  as  a  mechanical  stimulus 
to  the  inhibitor  elements  situated  in  the  domain  of  the  sino-auricular 
groove  (Remak's  ganglion).  Curiously  enough,  if  a  second  ligature 
is  now  applied  to  the  heart  at  the  auriculo ventricular  junction,  all 
three  parts  of  the  organ  again  contract,  but  their  beats  are  no  longer 
coordinated.  This  phenomenon  is  difficult  to  explain  unless  it  is  as- 
sumed that  the  second  ligature  stimulates  certain  accelerator  elements 
situated  in  the  region  of  the  auriculoventricular  groove  (Bidder's 
ganglion).  This  favors  the  production  of  an  independent  rhythm 
in  the  auricles  and  ventricle. 

The  Cause  of  the  Inhibition. — It  need  scarcelj'  be  mentioned  that 
the  activation  of  a  tissue  is  always  associated  with  the  destruction  of 

1  For  a  more  detailed  discussion,  see  Cushing's  Pharmacology  and  Therapeutics, 
London,  1915. 


CARDIAC    INHIBITION    AND    ACCELERATION  319 

certain  of  its  constituents.  This  phase  of  disintegration,  however, 
must  always  be  followed  by  a  period  during  which  the  material  lost 
is  again  replenished.  In  other  words,  catabolism  must  be  succeeded 
by  anabolism,  otherwise  the  destruction  of  the  living  material  becomes 
complete.  In  accordance  with  Claude  Bernard,  the  state  of  inhibition 
is  merely  a  prolonged  period  of  rest,  made  necessary  by  the  fact  that 
cardiac  muscle,  when  stimulated,  requires  an  unusually  long  time  for 
its  processes  of  restitution.  Hering  and  Gaskell  have  gone  one  step 
farther  and  have  suggested  that  the  vagus  possesses  a  true  construc- 
tive function  in  that  it  favors  the  occurrence  of  metabohc  changes. 
Thus  it  is  held  that  the  excitation  of  the  vagus  not  only  promotes 
the  continuance  of  that  intensity  of  anabolism  which  is  usual  during 
diastole,  but  actually  augments  the  processes  of  breaking  down  and 
building  up.  These  data  have  been  made  use  of  by  GaskelP  in  the 
formation  of  the  so-called  trophic  theory  of  inhibition.  The  conten- 
tion is  that  the  inhibitor  fibers  which,  as  has  been  shown,  are  generally 
included  in  the  vagus  nerve,  may  be  looked  upon  as  constituting  an 
anabolic  nerve  of  the  heart  and  must,  therefore,  be  of  greatest  impor- 
tance to  the  nutritive  processes  going  on  in  this  organ.  In  accordance 
with  this  view,  the  after-effects  of  their  excitation  must  be  very  bene- 
ficial, because  a  greater  formation  of  contractile  material  must  result 
therefrom  which  in  turn  insures  an  increased  functional  capacity  of 
the  musculature.  In  order  to  strengthen  this  theory,  Gaskell  has 
attempted  to  prove  that  these  trophic  alterations  are  associated  with 
definite  electrical  changes.  It  has  been  known  for  a  long  time  that 
the  active  part  of  a  tissue  is  electronegative  to  its  resting  part. 
Quite  similarly,  it  may  be  assumed,  in  accordance  with  the  preceding 
exposition,  that  the  inhibited  area  of  the  heart  is  electropositive  to  the 
non-inhibited.  In  order  to  prove  this  point,  the  auricles  of  a  turtle's 
heart  were  rendered  inactive  by  separating  them  from  the  sinus 
venosus.  One  of  the  poles  of  a  galvanometer  was  then  connected 
with  the  base  of  the  auricles,  while  the  other  was  permitted  to  rest 
upon  the  apical  region  which,  however,  had  previously  been  injured 
by  heat.  To  begin  with,  therefore,  the  aforesaid  instrument  registered 
a  demarcation-current,  the  direction  of  which  indicated  an  electro- 
negativity at  the  injured  apex.  If  the  auricles  were  now  made  to 
contract,  this  "current  of  injury,"  immediately  gave  way  to  a  "current 
of  action. "  Moreover,  if  the  vagus  nerve  was  stimulated  at  this  time,  a 
positive  variation  resulted,  indicating  the  production  of  an  electrical 
change  opposite  in  potential  to  that  encountered  during  the  contrac- 
tion of  these  parts. 

Another  theory  which  is  based  upon  the  well-known  fact  that 
potassium  salts  promote  the  relaxation  of  the  cardiac  musculature, 
has  been  proposed  by  Howell  and  Duke.^  It  is  held  by  these  authors 
that  the  stoppage  of  the  heart  is  dependent  upon  the  liberation  of 

»  Jour,  of  Physiol.,  vii,  1886,  451. 
^  Am.  Jour,  of  Physiol.,  xxi,  1908. 


320       THE  NERVOUS  REGULATION  OF  THE  HEART 

potassium  which,  on  being  set  free,  temporarily  inhibits  the  systolic 
processes.  Several  facts  might  be  cited  in  support  of  this  view.  Thus 
it  has  been  shown  that  this  salt,  when  added  in  certain  amounts  to  the 
perfusion  fluid,  gives  rise  to  a  diastolic  arrest  of  the  heart  which  closely 
resembles  that  resulting  from  the  excitation  of  the  vagus.  Cnder 
these  conditions,  the  inhibitor  power  of  the  vagus  may  be  restored  at 
any  time  by  simply  removing  the  excess  of  the  potassium.  Use  is 
also  made  of  the  observation  that  this  salt  exists  in  large  quantities 
in  cardiac  muscle  and  that  a  heart  gives  off  unusual  amounts  of  dif- 
fusible potassium  whenever  it  is  inhibited  with  the  aid  of  the  vagus. 
In  accordance  with  the  aforesaid  theory,  it  is  held  that  the  vagus 
impulses  incite  a  cleavage  of  some  kind  of  the  combined  tissue-potas- 
sium so  that  some  of  it  is  set  free  in  a  soluble  form.  The  subsequent 
interaction  between  the  potassium  thus  rendered  available  and  the 
cells  of  the  heart,  occurs  chiefly  in  that  region  in  which  the  beat  origi- 
nates. The  latter  amplification  of  this  theory  serves  to  explain  the 
fact  that  an  inhibited  heart  retains  its  irritability  toward  direct 
stimulation.  Hemmeter^  has  attempted  to  test  this  theory  experi- 
mentally by  analysis  of  the  ash  of  the  blood  contained  in  inhibited 
hearts,  as  well  as  by  arresting  the  activity  of  a  normally  beating  heart 
by  supphdng  it  directly  with  the  blood  of  an  inhibited  organ.  The 
results  of  these  experiments,  however,  have  failed  to  substantiate 
the  preceding  contentions  so  that  they  cannot  be  regarded  as  having 
been  removed  from  the  realm  of  a  mere  hypothesis. 

The  Result  of  the  Inhibition. — It  may  be  inferred  from  the  above 
discussion  that  the  inhibitor  mechanism  does  not  cease  its  activity  at 
any  time.  Impulses  are  discharged  by  the  cardiac  center  with  rhythmic 
regularity.  They  are  then  conducted  to  the  heart,  where  they  tend 
to  hold  this  organ  in  check.  In  this  way,  the  automatic  activity 
of  this  organ  is  subjected  to  a  constant  restraint  with  the  result  that  a 
normal  frequency  and  amplitude  of  contraction  is  obtained.  But 
whenever  this  check  is  removed,  the  accelerator  influences  gain  the  upper 
hand  and  finall}^  produce  an  augmentor  effect.  In  an  experimental 
way  these  inhibitor  impulses  may  be  prevented  from  reaching  the 
periphery  by  simply  dividing  the  conducting  path  (Fig.  169).  Obvi- 
ously, therefore,  the  section  of  the  vagi  nei'ves  must  lead  to  an  in- 
crease in  the  rate  of  the  heart,  and  naturally,  this  increase  must  be- 
come the  more  evident,  the  less  the  original  frequency  of  contraction. 

These  constant  discharges  from  the  inhibitor  center  may  also  be 
blocked  by  cooling  the  vagi  nerves  at  any  point  of  their  course,  or  by 
moistening  them  with  an  agent  which  diminishes  their  conductivity, 
for  example,  with  magnesium  sulphate.  In  this  connection  it  should 
be  emphasized  again  that  the  inhibitor  power  of  these  nerves  is  not 
equal  and  hence,  their  division  is  usually  followed  by  varying  degrees 
of  acceleration.  Thus,  it  maj'  happen  that  the  section  of  only  one  of 
the  vagi  nerves  produces  scarcely  any  acceleration,  while  the  division 
1  Biochem.  Zeitschr.,  1914,  63. 


CARDIAC    IXIIIBITION    AND    ACCELERATION 


321 


of  the  other  nerve  ulone  sullices  to  give  a  maximal  eH'cct.  Either  the 
right  or  the  left  nerve  may  be  the  more  powerful.  It  need  scarcely  be 
mentioned  that  these  inhibitor  reactions  may  also  be  incited  by  the 
stimulation  of  the  distal  end  of  the  (hvidcd  vagus,  the  electrodes  being 
apphed  either  to  the  right  or  to  the  left  nerve.  In  some  animals 
(cat)  it  is  also  possible  to  produce  a  moderate  inhibition  by  stimulating 
the  central  stump  of  either  vagus,  provided,  of  course,  that  the  opposite 
nerve  has  been  left  intact.     This  effect  is  easily  explained,  because 


fSrO  ■>*t,^^. 


Illl*il«#flilt 

117. 

/oo 

1                          i 

to        /                                       ^ 
o 

Fig.  169. — To  Show  the  Effect  of  Section  of  the  Two  Vagi  in  the  Dog  Upon  the 
Rate  of  Heart  Beat  Arn>  the  Blood- pressure. 
1,   Marks  the  section  of  the  vagus  on  the  right  side;  2,  section  of  the  second  vagus. 
The  numerals  on  the  vertical  mark  the  blood-pressures;  the  numerals  on  the  blood- 
pressure  record  give  the  rate  of  the  lioart  beats.     (Dawson.) 


these  nerves  also  conduct  impulses  from  the  heart  to  the  center,  where 
they  affect  the  cardiomotor  mechanism  in  a  reflex  wa^^  In  most 
cases,  these  afferent  stimuli  give  rise  to  an  inhibition,  but  it  also 
happens  at  times  that  they  incite  a  sHght  augmentation.  This  result 
is  usually  observed  in  dogs. 

If  the  blood  pressure  is  registered  during  these  stimulations  of 
the  vagus  nerve,  it  can  readily  be  established  that  the  inhibition  of  the 
heart  is  associated  with  a  fall  in  the  arterial  and  a  rise  in  the  venous 

21 


322        THE  NERVOUS  REGULATION  OF  THE  HEART 

pressure/  These  changes  prove  very  clearly  that  the  stoppage  of 
this  organ  is  followed  by  a  gradual  transfer  of  the  arterial  blood  into 
the  central  veins,  right  auricle  and  ventricle.  We  obtain,  therefore,  a 
condition  very  similar  to  that  found  at  death,  when  the  recoihng  ar- 
teries force  the  blood  into  the  venous  collecting  channels.  The 
arterial  blood  pressure  rises  again  with  the  return  of  the  cardiac  con- 
tractions. The  venous  pressure  drops  proportionately.  It  is  to  be 
noted,  however,  that  the  systoles  occurring  directly  after  the  inhibition 
cause  more  decided  changes  than  those  taking  place  later  on,  because 
the  gradual  refilhng  of  the  arterial  system  and  returning  tension  must 
necessarily  lead  to  a  corresponding  diminution  of  the  systolic-diastolic 
difference  in  pressure.  When  the  cardiac  output  has  again  become 
normal,   the  pressures  assume   their  former   level.     In  most  cases, 


Fig.  170. — Record  of  Carotid  Blood-pressure. 
.S,  stimulation  of  left  vagus  nerve.     The  fall  in  pressure  is  followed  by  compensatory 
changes  before  the  normal  pressure  is  again  established.  , 

however,  the  arterial  pressure  does  not  become  constant  until  it  has 
first  risen  somewhat  above  its  normal  value.  In  fact,  this  initial 
rise  above  normal  is  frequently  followed  by  a  fall  below  normal. 
These  oscillations,  occurring  in  the  wake  of  the  inhibition,  are  depend- 
ent upon  the  attempt  on  the  part  of  the  arterial  system  to  compensate 
for  the  loss  in  pressure.  To  begin  with,  the  arteries  constrict  more  and 
more,  as  the  blood  leaves  them  to  enter  the  veins.  In  this  condition, 
they  remain  until  the  first  ventricular  discharge  subsequent  to  the 
inhibition  again  distends  them.  The  resistance  thus  placed  in  the  path 
of  the  successive  cardiac  outputs  tends  to  raise  the  pressure  rather 
abruptly  so  that  its  normal  value  is  temporarily  exceeded.  At  this 
very  moment  the  vasoconstriction  gives  way  to  a  vasodilatation  with 
1  Burton-Opitz,  Am.  Jour,  of  Physiol.,  ix,  1903.  198. 


CARDIAC    INHIBITION    AND    ACCELERATION 


323 


the  result  that  the  pressure  now  falls  somewhat  below  its  normal  level. 
Subsequent  to  this   point  normal   conditions  are  again  established. 

As  might  be  expected,  these  compensatory  changes  are  not  always 
of  the  same  intensity,  because  the  irritability  of  the  vasomotor  mech- 
anism differs  in  the  same  degree  as  that  of  the  entire  ncu'vous  system. 
It  is  obvious,  however,  that  a  close  reflex  correlation  exists  between  the 
cardiac  and  vasomotor  centers,  so  that  a  reduction  in  the  ventricular 
output  may  be  compensated  for  unmediately  by  a  constriction  of 
the  blood-vessels.  This  is  of  greatest  importance,  because  the  functions 
of  the  different  colonies  of  cells  in  our  body 
must  necessarily  cease,  if  the  pressure  under 
which  they  obtain  their  nutritive  material 
falls  below  a  certain  minimal  value.  For 
this  reason,  even  a  relatively  brief  inhibi- 
tion of  the  heart  must  be  associated  with 
a  general  depression  of  function  which 
makes  itself  felt  most  strikingly  by  a  loss  of 
our  psychic  activities.  If  continued  for  an 
undue  length  of  time,  the  inhibition  must 
necessarily  be  followed  by  certain  disturb- 
ances of  function  which  are  not  so  easily 
compensated  for  and  remedied.  The  "es- 
cape of  inhibition"  may  be  said  to  consti- 
tute a  safety  device  of  the  body  to  prevent 
fatal  consequences  from  this  source. 

The  Character  and  Nature  of  the  Ac- 
celeration.— The  action  of  the  accelerator 
fibers  may  be  tested  experimentally  in 
mammals  as  well  as  in  lower  forms.  In 
the  former,  these  fibers  may  be  isolated  dis- 
tally  to  the  thoracic  sympathetic  ganglia, 
while  in  the  frog  and  allied  animals,  they 
may  be  rendered  accessible  directly  beside 
the  vertebral  column.  As  is  indicated  in 
Fig.  171,  the  latter  eventually  unite  with 
those  of  the  vagus  and  finally  terminate 
in  the  heart.  The  cardiomotor  fibers,  therefore,  may  be  reached  in 
this  animal  in  three  different  places.  Their  stimulation  at  A,  where 
the  vagus  alone  is  affected,  results  in  an  inhibition,  while  the  stimula- 
tion of  the  sympathetic  chain  at  B  gives  acceleration.  For  reasons 
discussed  previously,  the  excitation  of  the  vagosympathetic  at  C  is 
followed  by  an  inhibition. 

The  accelerators  produce  their  effect  after  a  considerable  latent 
period,  but  when  once  estabhshed,  the  acceleration  continues  as  a  rule 
for  some  moments  after  the  cessation  of  the  excitation.  Ten  or 
twenty  seconds  frequently  elapse  before  a  marked  increase  in  the 
cardiac  rhythm  is  observed,  while,  in  the  case  of  the  vagus,  the  latent 


Fig.  171.  —  Schema  to 
Show  the  Course  of  the  Car- 
diac Ner\-es  in  the  Frog. 

A,  vagal  fibers  are  still 
separate;  B,  sympathetic  fibers 
are  still  separate;  C,  both 
tjTjes  of  fibers  have  combined 
to  form  the  vagosympathetic 
nerve.  2,  Remak's  ganglion; 
B,  Bidder's  ganglion. 


324       THE  NERVOUS  REGULATION  OF  THE  HEART 

period  is  less  than  one  second.  Clearly,  therefore,  the  sympathetic  or 
accelerator  fibers  react  more  sluggishly  but  are  less  easily  fatigued 
than  the  inhibitor.  The  effect  of  their  excitation  consists  either  in  an 
acceleration  or  in  an  augmentation;  in  fact,  in  some  cases  both  changes 
are  obtained  simultaneously,  the  contractions  becoming  more  frequent 
as  well  as  more  forcible.  In  explaining  this  result,  it  is  generally 
stated  that  the  accelerator  mechanism  is  adjusted  in  such  a  way 
that  it  may  give  rise  to  two  reactions,  namely,  an  increase  in  the 
frequency,  and  an  augmentation  in  the  amplitude  of  the  individual 
beats.  In  analogy  with  this  functional  dissociation,  it  is  also  held  that 
the  inhibitor  mechanism  is  adjusted  in  such  a  way  that  the  inhibition 
may  be  accomplished  either  by  lessening  the  frequency,  or  by  decreas- 
ing the  amplitude  of  the  cardiac  contractions.^ 

While  the  experimental  evidence  is  not  very  conclusive,  it  has  been 
suggested  that  the  accelerator  center  discharges  its  impulses  in  rhyth- 
mic succession,  thereby  establishing  the  so-called  accelerator  tonus  in 
antagonism  to  the  inhibitor  tonus.  The  removal  of  the  former  influ- 
ence, therefore,  places  the  inhibitor  discharges  in  complete  control. 
A  slowing  of  the  heart  is  the  result  of  this  disturbance  of  the  cardio- 
motor  equilibrium.  This  end  can  be  attained  either  by  dividing  the 
accelerator  fibers  themselves,  or  by  removing  the  intrathoracic  ganglia. 
Upon  this  basis  cardio-acceleration  may  be  explained  by  assuming  that 
the  inhibitor  tonus  is  temporarily  diminished.  ^ 

The  increase  in  the  rate  of  the  heart  is  made  possible  by  a  shorten- 
ing of  each  cardiac  cycle,  the  duration  of  the  diastolic  period  being 
reduced  first  of  all.  It  may  be  stated  in  general  that  the  simultaneous 
occurrence  of  accelerator  and  augmentor  influences  gives  rise  to  a  higher 
blood  pressure  and  more  effective  circulatory  conditions  than  one 
of  these  reactions  alone  could  possibly  produce.  Thus,  a  simple 
acceleration  may  fail  absolutely  in  improving  hemodynamical  condi- 
tions for  the  obvious  reason  that  a  greater  number  of  ventricular 
discharges  alone  does  not  suffice  to  increase  the  cardiac  output  per  unit 
of  time,  because  the  filling  power  or  power  of  relaxation  of  the  heart 
may  have  been  diminished  in  a  measure  to  offset  the  increased  rate. 

The  Afferent  or  Cardiosensory  Fibers.— These  fibers  are  divided  into 
two  groups,  namely,  those  which  bring  the  cardiac  center  into  relation 
with  the  various  regions  of  the  body,  and  those  which  connect  it  with 
the  heart  and  neighboring  pericardial  and  mediastinal  membranes. 
The  first  group  embraces  a  large  number  of  nerves,  because  practically 
any  one  of  the  afferent  paths  in  our  body  may  at  times  convey  impulses 
to  central  parts  which  here  affect  the  activity  of  the  heart  in  a  reflex 
manner.     The  second  group  includes  the  ordinary  sensory  nerves 

1  Bayliss  and  Starling,  Jour,  of  Physiol.,  xiii,  1892,  407. 

2  Several  cases  have  been  recorded  of  persons  who  could  voluntarily  increase 
their  heart  rate  (West  and  Savage,  Arch.  Int.  Med.,  1918,  298).  The  acceleration 
was  accompanied  by  an  augmentation  of  the  respiratory  movements  and  a  dilatation 
of  the  pupils. 


CARDIAC    INHIBITION    AND    ACCELERATION 


325 


SL 


V 


of  tho  cardiac  region  and  also  a  number  of  inherent  fibers  which  are 
commonly  d(>siKuat('d  as  the  depressor  nerve.  The  latter  arise  in  the 
plexus  cardiacus  and  use  the  hij^hway  of  the  vagus  nerve  in  rea(!hing 
the  medulla  oblongata.  In  the  rabbit,  they  pursue  a  separate  course, 
entering  the  vagus  by  two  rami,  one  of  which  unites  with  the  superior 
laryngeal  nerve. 

If  we  confine  ourselves  for  the  present  to  the  general  type  of 
cardio-afferent  nerves,  it  will  be  noted  that  the  cardiac  center  is  con- 
stantly played  upon  by  various  impulses  which 
reach  it  through  the  different  afferent  channels  c    ^ 

of  our  body  and  are  then  transferred  either  to 
the  cardio-accelerator  or  cardio-inhibitor  mechan- 
ism. Thus,  while  the  heart  is  capable  of  con- 
tracting independently  of  its  center  as  well  as  of 
the  rest  of  the  body,  its  activity  is  regulated 
under  normal  conditions  in  such  a  manner  that 
it  fully  conforms  to  the  functions  of  other  organs 
and  tissues.  Naturally,  this  correlation  can  only 
be  attained  with  the  aid  of  diverse  afferent  im- 
pulses which  are  poured  into  the  cardiac  center 
at  different  times  and  vary  its  automatic  dis- 
charges so  as  to  give  the  results  previously  de- 
scribed. We  are  dealing,  therefore,  at  this  time 
with  typical  cardiac  reflexes. 

This  statement  raises  the  question  of  whether 
the  automatic  activity  of  the  cardiac  center  is 
maintained  by  stimuli  which  are  generated  by  its 
constituents,  or  whether  these  stimuli  are  con- 
veyed to  it  from  other  parts  of  the  body.  Al- 
though little  is  known  regarding  the  peculiar  pro- 
cesses occurring  in  ganglion  cells,  it  may  be 
assumed  that  nervous  impulses  result  in  con- 
sequence of  certain  physicochemical  alterations 
within  the  cell.  It  is  a  well-known  fact,  how- 
ever, that  intracellular  reactions  of  this  kind 
cannot  continue  for  an  indefinite  period  of  time 
unless  extraneous  influences  are  at  hand  to  cause 
these  internal  changes  to  be  repeated.  Cellular 
retrogression  and  disintegration  always  follow  in 
the  wake  of  loss  of  stimulation.  The  constit- 
uents of  the  cardiac  center  do  not  form  an  exception  to  this  rule, 
because  the  permanent  removal  of  these  afferent  stimuli  soon  reduces 
them  to  a  state  of  inactivity.  For  this  reason,  it  may  justly  be  as- 
sumed that  the  normal  tone  of  these  ganglion  cells  is  largely  dependent 
upon  reflex  stimulation. 

To  summarize,  the  activity  of  the  heart  is  normally  regulated  by 
the  cardiac  center,  the  discharges  of  which  are  constantly  varied  in 


Fig.  172  — Diagram 
TO  Show  the  Course 
OF  THE  Depressor 
Nerve  m  teie    Rabbit. 

L,  larynx;  T,  thyroid 
gland;  J,  int.  jugular 
vein;  C,  carotid  artery; 
S,  sympathetic  nerve 
extending  between  the 
superior  and  inferior 
cervical  ganglia;  V, 
vagus  nerve;  SL,  sup. 
laryngeal  nerve;  Z>,  de- 
pressor nerve,  entering 
the  vagus  by  two 
branches.  The  vagus 
is  pulled  over,  permit- 
ting the  sympathetic  to 
appear  next  to  the  caro- 
tid artery. 


326       THE  NERVOUS  REGULATION  OF  THE  HEART 

accordance  with  the  character  of  the  afferent  impulses  received  by  it. 
Two  views  are  held  regarding  the  nature  of  this  control.  In  the  pres- 
ence of  an  accelerator  and  inhibitor  mechanism,  it  is  believed  that  the 
cardiac  musculature  is  constantly  under  the  influence  of  two  types  of 
impulses  which  are  antagonistic  to  one  another  in  so  far  as  the  first 
tends  to  increase,  and  the  second  to  decrease  the  contractions.  Con- 
sequently, the  cardiac  frequency  must  be  regarded  as  the  product  of 
the  interaction  between  these  two  factors.  The  afferent  impressions 
received  by  the  center  shift  the  balance  either  in  the  direction  of  accel- 
eration or  inhibition.  They  accomplish  this  end  by  causing  a  greater 
number  of  impulses  of  either  the  former  or  latter  kind  to  be  generated 
and  to  be  conducted  to  the  heart.  In  accordance  with  the  second 
view,  it  is  held  that  the  activity  of  the  heart  can  only  be  increased  by 
a  depression  of  the  inhibitor  mechanism.^  Thus,  it  is  assumed  that 
the  afferent  impulses,  on  reaching  the  cardiac  center,  lessen  the  re- 
straint under  which  the  heart  is  constantly  held,  and  thereby  permit 
the  accelerator  influences  to  gain  full  power.  In  the  absence  of  defi- 
nite facts,  it  is  somewhat  difficalt  to  decide  which  of  these  two  processes 
is  normally  at  work.  It  would  seem,  however,  that  the  frequency  of 
the  heart  is  regulated  under  normal  conditions  solely  by  the  inhibitor 
center,  slight  changes  in  the  rate  of  contraction  being  effected  bj^  altera- 
tions in  the  tonus  of  the  latter.  Greater  variations  as  well  as  aug- 
mentor  effects,  however,  necessitate  an  active  opposition  to  the  in- 
hibitor influences  by  the  accelerator  center.  For  this  reason,  the 
latter  may  really  be  regarded  as  an  aid  to  the  former;  its  active 
participation  being  required  whenever  especially  marked  results  are 
to  be  obtained. 

It  has  been  stated  above  that  almost  all  sensory  nerves  convey 
afferent  impulses  to  the  cardiac  center  and  hence,  practically  all  recep- 
tors are  in  communication  with  the  cardiomotor  mechanism.  Chief 
among  these  are  the  retina,  the  organ  of  Corti,  the  semicircular  canals, 
the  olfactory  cells,  the  taste-buds,  as  well  as  the  cutaneous  and  visceral 
end-organs  for  touch,  pain,  and  temperature.  The  impressions  de- 
rived from  these  sources,  become  operative  either  directly  after  their 
reception  or  some  time  later  after  they  have  been  associated  in  their 
respective  intracerebral  centers.  In  the  latter  case,  the  stored  im- 
pulses which  serve  as  expressions  of  our  psychic  Ufe  or  belong  to  the 
group  of  the  emotions,  need  not  affect  solely  the  activity  of  the  heart, 
but  may  also  involve  respiration,  secretion,  as  well  as  the  responsive- 
ness of  smooth  and  striated  muscle-tissue.  In  general,  it  may  be  stated 
that  pleasurable  experiences  decrease  and  annoying  impressions 
increase  the  cardiac  rate.  It  should  also  be  noted  that  these  afferent 
impulses  may  give  rise  to  effects  which  actually  endanger  the  life  of 
the  individual.  As  an  example  of  this  kind  might  be  mentioned  the 
so-called  "reflex  cardiac  death"  which  may  result  whenever  the  in- 
hibitor center  is  excessively  stimulated.  It  should  also  be  mentioned 
1  Hunt,  Am.  Jour,  of  Physiol.,  ii,  1899,  395. 


CARDIAC    INHIBITION    AND    ACCELERATION  327 

tliat  while  the  action  of  the  heart  cannot  usually  be  influenced  by 
volition,  certain  cases  are  on  record  which  clearly  prove  that  a  marked 
voluntary  control  over  this  organ  may  be  acquircul  at  times  quite  iiuU^- 
pendently  of  emotional  states  or  remote  sensorj'  impressions.' 
These  volitional  efforts  most  commonly  produce  an  acceleration,  but 
may  also  induce  a  slowing  of  the  heart. 

The  frequency  of  the  heart  may  also  be  lessened  by  exerting  a  slight 
pressure  uiwn  the  vagus  at  any  point  of  its  course;  along  the  neck.' 
As  this  procedure  is  not  without  danger,  it  should  only  be  practised 
with  the  greatest  care.  Augmentor  or  inhibitor  effects  frequently 
result  from  tumors  or  serous  effusions  affecting  either  the  medulla  or 
the  cardiac  nerves  themselves.  It  should  also  be  remembered  that 
the  activity  of  the  cardiac  center  is  closely  related  to  that  of  the 
neighboring  respiratory  center,  as  is  shown  l)y  the  fact  that  the  fre- 
quency of  the  heart  increases  during  inspiration.^  This  reaction  ap- 
pears in  the  nature  of  a  reflex  which  seems  to  have  its  origin  in  a  central 
stimulus  rather  than  in  one  generated  in  the  lungs  themselves.  Two 
or  three  reasons  may  be  given  for  this  view.  Thus,  it  has  been  found 
that  it  persists  during  the  spasmodic  respiratory  attempts  following 
the  division  of  the  cervical  portion  of  the  spinal  cord,^  and  that  it  is  not 
in  evidence  in  certain  animals.  This  acceleration  may  be  made  more 
striking  by  increasing  the  amplitude  of  the  respiratory  motions  or  by 
heightening  the  general  irritability  of  the  central  nervous  system.^ 
It  has  been  suggested  by  Spalitta"  that  the  stimuli  upon  which  this 
reflex  depends,  arise  in  the  muscles  normally  employed  in  inspiration. 
Deglutition  possesses  a  similar  influence,  the  cardiac  acceleration  be- 
coming the  more  marked,  the  greaterthefrequency  of  these  movements. 
The  opposite  result  may  be  produced  by  stimulating  the  mucous  mem- 
brane of  the  nasal  cavity  with  the  vapors  of  chloroform  or  other  irri- 
tants.    This  constitutes  the  so-called  cardiac  trigeminus  reflex. 

An  intimate  functional  connection  also  exists  between  the  heart 
and  the  systemic  blood-vessels,  because  a  higher  arterial  tension  is 
generally  compensated  for  by  a  lessening  of  the  activity  of  this  organ, 
while  a  low  pressure  gives  rise  to  augmentor  effects.  Although  the  reflex 
character  of  these  changes  cannot  be  questioned,  some  doubt  exists 
as  to  the  precise  locality  in  which  these  primary  stimuH  are  produced. 
Thus,  it  may  be  assumed  that  they  arise  in  consequence  of  the  varying 
distention  of  the  blood-vessels,  but  it  is  also  possible  that  they  are 
generated  in  the  heart  itself,  because  this  organ  is  equipped  with  sen- 
sory corpuscles  sunilar  to  those  found  in  other  structures.^  It  is  more 
than  probable  that  the  high  arterial  pressure  tends  to  stimulate  these 

1  Tarchanoff,  Pfliiger's  Archiv.,  xxxv,  1885,  and  van  de  Velde,  ibid.,  Ixvi,  1897. 

^  Thanhoffer,  Centralbl.  fiir  die  med.  Wissensch.,  1875. 

3  First  observed  by  C.  Ludvvig  (Miiller's  Archiv.,  1847). 

■*  Fredericq,  Archiv  de  Biol.,  iii,  1882. 

*  Henderson,  Am.  Jour,  of  Physiol.,  xxxi,  1913,  399. 

6  Arch.  ital.  de  Biol.,  xxx-v,  1901. 

"  Smirnow,  Anat.  Anzeiger,  x,  1895. 


328       THE  NERVOUS  REGULATION  OF  THE  HEART 

end-organs  by  causing  an  overdistention  of  the  ventricular  cavities 
or  at  least  of  the  root  of  the  aorta.  This  conception  finds  support  in 
the  fact  that  even  a  moderate  compression  of  the  heart,  as  results 
during  the  act  of  coughing  or  laughing,  is  usually  associated  with  an 
acceleration,  while  the  irritation  of  the  endocardium  most  generally 
gives  rise  to  inhibitor  effects.^  Less  probable  is  the  view  that  these 
changes  are  occasioned  by  a  direct  action  of  the  blood  pressure  upon 
the  constituents  of  the  cardiac  center. ^ 

One  of  the  first  proofs  of  the  existence  of  these  cardiovascular 
reflexes  has  been  furnished  by  Goltz^  who  found  that  the  frequency 
of  the  heart  may  be  reduced  by  simply  tapping  upon  the  surface  of 
the  abdomen  of  a  frog  with  a  flat  instrument.  As  this  effect  is  not 
obtained  after  the  vagi  nerves  have  been  divided,  there  can  be  no  ques- 
tion regarding  the  reflex  character  of  these  impulses.  On  the  afferent 
side,  their  course  may  be  either  over  the  nerves  of  the  cutaneous 
sensations  or  over  those  relegating  deep  sensibilities  from  the  viscera. 
The  latter  contention  seems  the  more  probable.  Very  similar  results 
are  obtained  in  mammals  in  consequence  of  the  mechanical,  thermal, 
electrical  or  chemical  stimulation  of  the  abdominal  viscera.  Among 
the  large  number  of  causes  for  this  reflex  may  be  mentioned  the  accumu- 
lation of  gas  in  the  stomach  or  intestine,^  inflammatory  processes  or 
irritations  of  these  organs  by  substances  contained  in  the  food,  and 
strokes  upon  the  region  of  the  solar  ganglia. 

The  cardiac  acceleration  commonly  associated  with  increases  in 
the  activity  of  the  skeletal  musculature,  may  be  explained  in  different 
ways.  Thus,  it  may  be  held  that  the  volitional  impulses  which  are 
generated  in  the  cerebral  hemispheres  and  are  then  conducted  to  the 
muscles,  overflow  and  affect  the  cardiac  center  directly.  It  may  also 
be  assumed  that  the  contractions  of  the  muscles  give  rise  to  mechan- 
ical impulses  which  influence  the  center  reflexly.  In  the  third  place, 
it  has  been  thought  possible  that  the  activity  of  the  center  may  be 
varied  by  certain  chemical  substances  formed  in  the  course  of  muscular 
exercise.  This  view  finds  confirmation  in  the  fact  that  the  function 
of  the  center  may  be  influenced  either  by  varying  the  amounts  of  blood 
supplied  to  it,  or  by  altering  the  oxygen  content  of  the  circulating 
blood.  Thus,  it  has  been  found  that  the  occlusion  of  the  carotid  and 
vertebral  arteries,  as  practised  by  Kussmaul  and  Tanner,  is  followed 
invariably  by  a  slowing  of  the  heart.  This  reaction,  however,  does 
not  result  if  the  vagi  nerves  have  been  divided  beforehand.  Very 
similar  effects  may  be  obtained  by  lessening  the  oxygen  content  or 
by  increasing  the  carbon  dioxid  content  of  the  blood.  Even  a  slight 
dyspneic  condition  suffices  to  augment  the  cardiac  beats  and  rate, 
while  a  more  intense  dyspnea  invariably  leads  to  partial  and  complete 

1  Pagano,  Archiv  ital.  de  Biol.,  xxxiii,  1900. 

2  Biedl  and  Reiner,  Pfliiger's  Archiv,  Ixxiii,  1898,  385. 

3  Virchow's  Archiv  fiir  path.  Anat.,  xxvi,  1863. 

*  Burton-Opitz,  Pfliiger's  Archiv,  cxxxv,  1908,  205. 


CARDIAC    INHIBITION    AND    ACCELEKATION 


329 


inhibition.  \o\y  ilvvidvd  clKingcs  in  the  frequency  of  \hv  heart  may 
also  be  produced  with  the  aid  of  the  cutaneous  end-ort^ans,  their 
activation  beinf;  effected  either  by  cold  or  warm  water,  mechanical 
impacts,  massage,  effervescent  water,  and  other  stimuli.  The  fact  that 
some  of  these  afferent  impulses  most  easily  elicit  inhibitor  and  others 
accelerator  phcniomena,  has  been  explained  l)y  assuming  that  they  may 
be  more  intimately  connected  either  with  the  cardio-inhibitor  or 
with  the  cardio-accelerator  mechanism.  In  the  case  of  the  carbonated 
water  bath,  however,  the  mechanical  stimulus,  consisting  in  the  bump- 
ing of  the  globules  of  the  gas  against  the  integument,  may  be  aug- 
mented by  a  direct  effect  of  the  carbon  dioxid  upon  the  cardiac  center. 
It  seems  entirely  probable  that  some  of  it  may  be  absorbed  and  then 
act  as  a  stimulant  not  only  to  the  respiratory  but  also  to  the  cardio- 
vascular system. 

As  has  been  emphasized  above,  the  cardiac  center  is  also  the  re- 
cipient of  sensory  impulses  which  arise  either  in  the  membranous 


Fig.  173.- 


-Record  of  the  Carotid  Blood-pressure  in  Rabbit  During  Stimulation 
OF  THE  Depressor  Nerve. 


structures  enveloping  the  heart,  or  in  this  organ  itself.  The  fibers 
conducting  the  impulses  from  the  heart  are  attributes  of  the  vagus 
system,  and  have  been  designated  by  Ludwig  and  Cyon,^  their  dis- 
coverers, as  the  depressor  nerve.  These  fibers  become  clearly  recogniz- 
able upon  the  arch  of  the  aorta,  whence  they  reach  the  vagus  center 
either  by  pursuing  an  independent  course  along  the  carotid  artery 
(rabbit),  or  by  intermingling  with  the  vagosympathetic  fibers  (dog). 
In  the  rabbit,  this  nerve  is  isolated  most  easily  in  the  neck,  where  it 
forms  an  anatomical  entity  next  to  the  inner  border  of  the  cervical 
sympathetic  and  the  trunk  of  the  vagus.  Centrally  to  this  point 
it  divides  into  two  slender  bundles,  one  of  which  enters  the  cervical 
portion  of  the  va^us  directly,  and  the  other,  the  superior  laryngeal 
branch  of  this  nerve.  The  fibers  of  both  branches  then  intermingle 
with  the  other  vagal  fibers. 

^  Berichte  der  sachs.  Akad.  der  Wissensch.,  1866. 


330       THE  NERVOUS  REGULATION  OF  THE  HEART 

The  depressor'  nerve  possesses  a  very  characteristic  and  important 
function.  It  is  sensory  in  its  nature  and  conducts  impulses  solely  from 
the  heart  to  the  nucleus  of  the  vagus  and  the  cardiac  and  vasomotor 
centers.  It  must  be  obvious,  therefore,  that  the  effects  ordinarily 
obtained  with  the  help  of  this  nerve,  can  only  be  elicited  by  stimulat- 
ing either  the  intact  nerve  or  its  central  end.  Concerning  its  function, 
it  may  be  stated  in  brief  that  it  gives  rise  to  reflexes  which  are  centered 
upon  the  cardiac  and  vasomotor  mechanisms.  The  former  produce 
a  reduction  in  the  frequency  of  the  heart  and  the  latter,  a  fall  in  arterial 
blood  pressure.  But  their  action  upon  the  heart  may  be  destroyed 
by  dividing  the  vagus  distally  to  its  point  of  union  with  the  depressor 
fibers.  Naturally,  the  drop  in  pressure  persists  even  after  the  division 
and  is  then  frequently  associated  with  an  increase  in  the  frequency 
of  the  heart.  ^ 

The  foregoing  data  show  very  clearly  that  the  depressor  nerve 
plays  an  important  part  in  varying  the  resistance  in  the  vascular 
channels  against  which  the  heart  must  act.  To  illustrate,  if  the  ar- 
terial tension  is  too  high,  an  impulse  is  set  up  in  this  organ  which,  on 
being  relayed  to  the  cardiac  and  vasomotor  centers,  produces  a  re- 
duction in  the  rate  of  the  heart  and  a  fall  in  the  blood  pressure.  Ob- 
viously, this  reflex  lessening  of  the  peripheral  resistance  places  the 
cardiac  muscle  in  a  much  more  favorable  position  to  contract  with- 
out strain. 

By  connecting  this  nerve  with  a  string  galvanometer,  Einthoven'^ 
has  shown  that  sensory  impulses  are  generated  synchronously  with 
every  contraction  of  the  heart,  but  naturally,  this  fact  does  not  signify 
that  the  "depressor-reflex"  is  elicited  an  equal  number  of  times.  No 
doubt,  these  impulses  remain  subminimal  as  a  rule,  and  although  trans- 
mitte/i  to  the  medulla,  serve  here  merely  the  purpose  of  maintaining  the 
tonicity  of  the  cardiac  center.  It  has  also  been  proved  by  Koster 
and  Tschermak^  that  electrical  variations  may  be  produced  in  this 
nerve  by  increasing  the  intra-aortic  pressure  artificially.  Inasmuch 
as  this  nerve  ramifies  extensively  upon  the  ascending  portion  of  the 
aorta,  it  may  be  surmised  that  these  sensory  impulses  arise  chiefly  in 
consequence  of  the  mechanical  stimulation  resulting  from  the  disten- 
tion of  this  blood-vessel  and,  in  a  lesser  degree,  also  from  the  disten- 
tion of  the  heart  itself. 

1  Bayliss,  Jour,  of  Physiol.,  xiv,  1893,  303. 

2  Pfliiger's  Archiv,  cxxiv,  1908,  246. 

^  Ibid.,  xciii,  1903,  24;  also  see:  Eyster  and  Hooker,  Am.  Jour,  of  Physiol.,  xxi, 
1908,  373. 


SECTION  IX 

FUNCTIONAL  PECULIARITIES  OF  THE  CARDIAC 
MUSCLE    TISSUE 


CHAPTER  XXVIII 
THE  ORIGIN  OF  THE  HEART  BEAT 

The  Excised  Heart. — If  the  heart  of  a  cold-blooded  animal  is  re- 
moved from  the  body  and  is  placed  in  a  nutritive  medium  under  proper 
conditions  of  moisture  and  temperature,  it  will  continue  to  beat 
rhythmically  for  many  hours,  and  even  for  days.  Essentially  the  same 
result  may  be  obtained  with  the  hearts  of  warm-blooded  animals,  but 
inasmuch  as  their  storative  power  is  slight,  they  require  a  constant 
supply  of  nutritive  material.  Thus,  it  wUl  be  found  that  the  mamma- 
lian heart  ceases  to  beat  very  soon  after  the  circulation  has  been  inter- 
rupted, but  may  be  made  to  resume  its  activity  later  on  by  perfusing 
it  through  its  coronary  blood-vessels.  This  procedure  consists  in 
connecting  the  aorta  with  a  pressure  reservoir  containing  an  0.8 
per  cent,  solution  of  sodium  chlorid,  Ringer's  fluid,  or  defibrinated 
blood  through  which  bubbles  of  oxygen  are  passed  at  a  constant  rate. 
Under  the  most  favorable  conditions  an  excised  heart  may  be  kept 
beating  rhythmically  for  many  hours ;  moreover,  if  it  is  merely  intended 
to  incite  the  contractions  without  having  them  continue  for  any  length 
of  time,  it  is  sufficient  to  use  oil  or  paraffin  in  place  of  the  nutritive 
fluids  just  mentioned.  Evidently,  the  mechanical  stimulus  derived 
from  the  distention  of  the  coronary  vessels  suflftces  to  activate  the 
musculature  and  to  keep  it  in  this  condition  for  a  moderately  long 
time.  These  experiments  may  be  repeated  with  smaller  segments  of 
the  heart  as  well  as  with  narrow  strips  of  the  ventricles.  In  the  latter 
case,  it  is  sufficient  to  immerse  them  in  solutions  of  certain  inorganic 
salts.  Larger  pieces  of  the  ventricles  may  be  made  to  beat  rhythmi- 
cally by  perfusing  them  through  their  supply  channel. 

The  conclusion  to  be  drawn  from  experiments  of  this  kind  is  that 
the  power  of  rhythmic  contraction  is  inherent  in  the  hearts  of  all 
vertebrates.^  Their  connection  with  the  central  nervous  system,  there- 
fore, is  not  essential  to  their  activity  and  merely  serves  the  purpose  of 
bringing  them  into  functional  relation  with  the  other  organs  and  tissues. 

It  has  previously  been  shown  that  various  conditions  may  arise  in 

1  First  taught  by  Haller  in  1757. 
331 


332  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

different  parts  of  the  body  which  influence  the  activity  of  the  heart 
by  way  of  these  connecting  channels.  These  correlating  impulses, 
however,  have  nothing  to  do  with  the  actual  cause  of  the  contractions. 
In  the  second  place,  it  must  be  evident  that  even  if  it  has  been  demon- 
strated that  the  beat  originates  in  the  heart,  it  still  remains  to  be  de- 
termined whether  the  impetus  to  contract  is  given  by  the  muscle 
substance  or  by  the  nervous  elements  contained  therein.  The  views 
held  pertaining  to  this  question  have  been  embodied  in  the  so-called 
neurogenic  and  myogenic  theories  of  the  heart  beat. 

Closely  related  to  this  problem  is  another  which  pertains  more 
directly  to  the  cause  of  the  orderly  sequence  of  the  contractions  of  the 
different  segments  of  the  heart.  Thus,  it  may  be  asserted  that  the 
rhji:hm  of  the  heart  is  associated  either  with  the  nervous  elements  or 
with  the  muscle  tissue.  With  reference  to  the  automaticity  of  this 
organ,  the  question  may  then  be  raised  whether  its  power  of  remaining 
active  by  a  self -inducing  cause  is  contained  in  the  first  or  in  the  second 
component'?  At  the  present  time  it  is  quite  impossible  to  give  a 
definite  answer  to  these  questions.  We  are,  however,  in  possession  of 
certain  fundamental  facts  relating  to  tliis  topic  wliich  may  best  be  pre- 
sented separately  under  the  headings  of  the  theories  just  mentioned. 

The  Neurogenic  Theory  of  the  Heart  Beat. — This  theory  which  has 
been  proposed  by  Volkmann,  was  strengthened  considerably  by  the 
discovery  of  Remak  that  the  heart  of  the  frog  gives  lodgment  to  nerve 
fibers  as  well  as  to  ganglion  cells  (1849).  Upon  entering  the  sinus 
venosus,  the  two  vagi  nerves  unite  to  form  a  plexus  which  is  situated 
below  the  pexicardium  and  embraces  numerous  ganglion  cells.  Re- 
mak's  ganglion  is  connected  by  means  of  two  septal  nerves  with  another 
network  of  nerve  tissue  which  is  situated  in  the  vicinity  of  the  auriculo- 
ventricular  groove  and  is  known  as  Bidder's  ganghon.  Both  ganglia 
send  non-medullated  fibers  to  the  neighboring  regions  of  the  auricles 
and  ventricle,  a  few  isolated  nerve  cells  being  interposed  here  and  there. 
It  was  also  noted  that  the  apical  portion  of  the  heart,  embracing  the 
lower  one-half  to  two-thirds  of  the  ventricle,  is  free  from  cellular 
elements.  Even  more  favorable  conditions  for  experimentation 
prevail  in  the  turtle,  because  the  heart  of  these  animals  is  larger  and  its 
nervous  elements  are  more  easily  accessible. 

In  accordance  with  this  theory,  it  is  assumed  that  the  successive 
cardiac  contractions  result  in  consequence  of  excitations  which  are  sent 
out  at  regular  intervals  bj"  the  cells  composing  the  aforesaid  gangha. 
IMoreover,  as  each  contraction  begins  near  the  venous  entrance  to  the 
right  auricle,  and  progresses  from  here  toward  the  apex,  Remak's 
ganghon  is  generally  regarded  as  the  motor  center  of  the  entire  organ. 
It  is  held,  therefore,  that  the  cause  of  the  automaticity  lies  within  these 
cells,  while  the  peripheral  fibers  and  cellular  elements  serve  merely  as 
adjuncts  which  are  made  use  of  in  the  conduction  of  the  wave  of 
excitation  to  other  parts  of  this  organ.  It  is  granted,  however,  that  the 
separation  of  these  outlying  elements  from  the  "pace-maker, "  enables 


THE    ORIGIN    OF    THE    llEAKT   BEAT 


333 


thorn  to  assumo  cortain  automatic  propcrtios  of  tlioir  own  and  to  acti- 
vate that  portion  of  the  niu.sculaturc  witii  which  tho}'  are  normally 
connected.  Essentially  the  same  explanation  is  {j^iven  for  the  mode  of 
contraction  of  the  mammalian  heart,  although  the  location  of  its 
nervous  elements  has  not  been  fully  ascertained  as  yet. 

It  should  be  stated  at  this  time  that  the  neurogenic  theory  in  its 
extreme  form  is  untenable,  and  while  a  number  of  experiments  could 
be  cited,  tending  to  emphasize  the  importance  of  the  nervous  elements 
as  the  controlling  factor  of  the  heart's  action,  the  evidence  is  not  suffi- 
ciently definite  to  prevent  us  from  interpreting  it  in  a  way  to  favor  the 
myogenic  theory.  The  same  objection,  however,  may  be  raised  against 
several  of  the  experiments  which  will  be  mentioned  later  on  in  support 
of  the  latter  theory,  because  they  permit  of  a  two-fold  interpretation, 
thus  favoring  one  view  as  much  as  the  other.  The  experimental 
evidence  so  far  presented  may  be  arranged  as  follows: 

1.  If  the  heart  of  a  frog  is  removed  in  its  entirety,  it  will  continue  to  beat  for  a 
long  period  of  time,  provided,  of  course,  that  it  is  placed  in  a  proper  nutritive  medium. 
If  it  is  then  cut  across  at  the  sino-auricular  groove,  its  sinus  continues  to  contract 


mnc      in  (a 

Fig.   174. — Heart  of  Limulus  from  DorsaIi  Surface.     (Carlson.) 
mnc,  Median  nerve-cord;  In,  lateral  nerve-trunks. 

at  regular  intervals,  while  its  auricles  and  ventricle  cease  beating  at  least  for  some 
time.  The  latter  then  resume  their  activity,  the  beat  seemingly  originating  in  the 
auricle.  Their  frequency  of  contraction,  however,  rarely  equals  the  normal.  If  the 
ventricle  is  then  separated  from  the  auricles  by  a  cut  across  the  auriculoventricular 
groove,  the  latter  continue  to  beat,  while  the  former  soon  ceases  its  activity.  A 
certain  time  having  elapsed,  the  ventricle  again  contracts  but  now  quite  independ- 
ently of  the  rhythm  of  the  other  segments  of  this  organ. 

2.  Very  similar  results  may  be  obtained  by  applying  two  ligatures  to  the  heart 
in  such  a  way  that  one  comes  to  lie  in  the  sino-auricular  groove  and  the  other,  in 
the  auriculoventricular  groove.  (Stannius  experiment,  1852.)  After  the  applica- 
tion of  the  first,  the  auricles  and  ventricle  cease  beating,  while  the  sinus  continues 
to  contract.  All  three  divisions,  however,  beat  at  regular  intervals  as  soon  as 
the  second  ligature  has  been  properly  placed  and  tightened.  As  Heidenhain  has 
stated,  the  first  ligature  seems  to  exert  a  mechanical  stimulus  upon  the  inhibitor 
ganglion,  while  the  second  serves  as  a  stimulant  for  the  accelerator  elements.  It  is 
to  be  noted,  however,  that  the  different  segments  of  the  heart  now  beat  inde- 
pendently of  one  another,  and  that  the  regular  progression  of  the  wave  of  con- 
traction from  the  sinus  to  the  apex  is  no  longer  in  evidence.  These  experiments 
tend  to  show  that  the  different  portions  of  the  heart  are  imbibed  with  a  certain 
automatic  power  of  their  own  which  diminishes  gradually  in  the  direction  from 
sinus  to  apex.  This  dormant  power  enables  the  more  distant  ganglia  to  originate 
impulses  at  any  time  after  the  more  central  elements  have  been  destroyed  or  have 
been  separated  from  them.  Since  the  property  of  automaticity  seems  to  be 
associated  exclusively  with  nerve  cells,  the  muscle  cells  find  themselves  in  the 
position  of  mere  executors  of  the  will  of  a  higher  controlling  factor. 


334  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

3.  By  cutting  and  removing  the  nerve  cord  which  passes  along  the  tubular 
heart  of  the  horseshoe  crab,  Carlson'  has  succeeded  in  showing  that  the  cause  of 
the  contraction  of  this  organ  lies  in  the  ganglion  cells  of  the  median  cord,  and  that 
the  conduction  is  effected  by  the  nervous  and  not  by  the  muscular  elements.  In 
this  particular  case,  therefore,  it  would  appear  that  the  cessation  of  the  heart  beat 
is  brought  about  by  an  interference  with  the  automatic  discharges  of  the  ganglion 
cells  (Weber)  and  not  by  an  inhil)ition  of  the  activity  of  the  cardiac  musculature 
(Engelmann).  These  results,  however,  do  not  permit  of  generalizations,  because 
they  cannot  justly  be  applied  to  the  vertebrate  heart  without  certain  modifications. 
The  reason  for  this  is  that  the  heart  of  vertebrates  may  possess  certain  physiological 
properties  which  are  very  different  from  those  displayed  by  the  heart  of  the 
crustaceans. 

4.  It  has  been  found  by  Kronecker  and  Schmey^  that  the  regular  and  forceful 
contractions  of  the  ventricle  may  be  changed  into  mere  fibrillary  undulations 
(delirium  cordis)  at  any  time  by  puncturing  the  interventricular  septum  at  a 
point  near  the  junction  of  its  upper  and  middle  thirds.  While  this  phenomenon 
has  been  interpreted  as  proving  that  the  coordinated  action  of  the  ventricle  is  de- 
pendent upon  a  center  situated  in  the  aforesaid  region,  this  hypothesis  can  scarcely 
be  defended  in  the  light  of  our  present  knowledge  regarding  the  conduction  paths 
of  the  heart.  Moreover,  it  has  been  shown  subsequently  by  McWilliams^  that 
the  cardiac  musculature  may  also  be  made  to  fibrillate  in  other  ways,  for  example, 
by  mechanical,  thermal,  and  electrical  stimulation  of  the  surface  of  the  heart  in 
the  vicinity  of  the  apex. 

5.  The  contractions  of  the  mammalian  heart  may  also  be  incited  by  perfusing 
the  coronary  circuit  with  non-nutritive  fluids.  It  seems  that  in  this  particular 
case  the  distention  of  the  coronary  blood-vessels  suffices  to  stimulate  the  nervous 
receptors  in  a  mechanical  way. 

The  Myogenic  Theory  of  the  Heart  Beat.^ — This  theory  has  been 
more  fully  developed  in  recent  years  by  the  work  of  Gaskell  and 
Engelmann.  It  is  held  that  the  wave  of  excitation  arises  in  the  muscle 
tissue  and  that  the  nervous  elements  serve  the  sole  purpose  of  cor- 
relating the  action  of  the  different  parts  of  the  heart,  and  secondly,  of 
bringing  the  activity  of  this  organ  into  functional  relation  with  other 
structures.  Furthermore,  as  the  beat  originates  in  the  venous  vesti- 
bule, the  tissue  composing  this  particular  area,  is  said  to  possess 
certain  functional  pecuUarities  which  render  it  especially  suitable  for 
the  generation  of  those  impulses  which  later  on  give  rise  to  the  con- 
traction. The  arguments  favoring  the  myogenic  theory  may  be  cited 
as  follows: 

1.  Bernstein's  Experiment. — If  the  apical  portion  of  the  heart  of  a  frog  or 
turtle  is  separated  by  a  ligature  which  is  tightly  drawn  around  the  ventricle,  it 
ceases  to  contract  almost  immediately.  When  isolated  in  this  way,  it  may  be  made 
to  beat  again  by  applying  electrical  or  mechanical  stimuli  to  its  surface  or  by  raising 
the  pressure  within  its  cavity.  The  latter  end  may  be  attained  at  times  by  tem- 
porarily comptessing  the  aortse. 

2.  Strips  of  tissue  may  be  cut  from  the  apex  which  may  be  made  to  beat 
rhythmically  by  placing  them  in  an  isotonic  solution  of  sodium  chlorid  or  in 
Ringer's  fluid.  These  strips  frequently  continue  their  activity  for  several  hours. 
These  experiments  become  especially  significant,  if  it  is  remembered  that  the  apex 
of  these  hearts  contains  no  ganglion  cells. 

1  Am.  Jour,  of  Physiol.,  xiii,  1905,  217. 

"^  Sitzungsber.  der  Akad.  der  Wissensch.,  Berlin,  1884. 

5  Jour,  of  Physiol.,  viii,  1887,  296. 


THE    ORIGIN    OF    THE    HEART   BEAT  335 

3.  In  the  frog  and  turtle  it  is  possible  to  remove  practically  the  entire  inter- 
auricular  septum,  together  witli  its  ganglia  and  connecting  paths,  without  inter- 
fering with  the  character  or  rhythm  of  the  cariliae,  contractions. 

4.  A  still  stronger  argument  is  contained  in  the  fact  that  tlie  embryonic  heart 
of  the  chick  (2  to  5  days)  or  shark  beat  with  perfect  regularity  at  a  time  when  as 
yet  no  ganglion  cells  can  be  made  out.  If  segments  of  the  embryonic  heart  are 
kept  ia  ii  medium  of  blood  plasma,'  they  will  continue  to  beat  for  a  long  time; 
indeed,  the  muscular  units  usually  multiply  under  this  condition  and  give  rise  to 
new  cells  which  possess  rhythmic  activity.  While  this  fact  clearly  proves  that 
the  cardiac  muscle  is  automatic,  it  may  be  contended  that  this  property  is  primi- 
tive and  of  short  duration,  and  that  it  is  eventually  superseded  by  the  auto- 
maticity  of  the  newly  developed  nervous  elements. 

5.  The  excised  bulbus  aorto)  of  the  frog,  and  even  portions  thereof,  usually  con- 
tinue to  contract  rhythmically.  The  same  result  may  be  obtained  with  small 
segments  of  the  veins  entering  the  sinus  venosus. 

6.  Rhythmic  contractions  may  be  observed  in  the  veins  of  the  wing  of  the  bat, 
as  well  as  in  certain  segments  of  the  lymphatic  system.  Nervous  elements  have 
not  been  demonstrated  in  these  tissues. 

7.  In  the  lower  forms,  the  wave  of  contraction  which  normally  starts  in  the 
sinus  portion  of  the  heart,  is  propagated  to  the  auricles  and  ventricles  by  means 
of  clearly  recognizable  strands  of  muscle  tissue.  Moreover,  while  the  conducting 
path  in  the  mammalian  heart,  as  represented  by  the  bundle  of  His,  is  formed  by  a 
type  of  tissue  which  cannot  justly  be  classified  as  muscle  tissue,  it  does  not  at  all 
possess  the  characteristics  of  nerve  tissue. 

8.  Waves  of  contraction  may  also  be  incited  in  other  parts  of  the  heart.  Thus, 
the  stimulation  of  the  apex  most  generally  gives  rise  to  a  contraction  in  a  direction 
opposite  to  normal,  namely,  from  ventricle  to  sinus. 

9.  Engelmann  has  shown  that  the  continuity  of  the  nerve  fibers  of  the  heart 
may  be  destroj^ed  without  materially  changing  the  sequence  of  its  contractions. 
Thus,  it  is  possible  to  convert  the  auricle  of  the  frog's  heart  by  several  transverse 
cuts  into  a  zig-zag  strip  without  blocking  the  wave  of  contraction  as  it  passes 
from  the  sinus  to  the  ventricle.  Very  similar  results  may  be  obtained  with  the 
ventricular  muscle.  If  changed  into  a  zig-zag  strip  by  transverse  incisions,  a 
contraction  started  in  its  basal  portion  eventually  reaches  the  apex,  while  a 
contraction  incited  at  the  apex  also  progresses  to  the  base. 

The  results  of  the  experiments  just  enumerated  indicate  with 
certainty  that  the  nervous  elements  of  the  heart  possess  the  power  of 
discharging  rhythmic  impulses  and  that  cardiac  muscle  tissue  is 
equipped  with  rhythmic  properties  similar  to  those  of  other  tissues. 
Smooth  muscle  and,  in  a  shght  degree,  also  striated  muscle  are  in 
possession  of  this  power.  It  may  be  contended,  however,  that  this 
primitive  functional  characteristic  of  cardiac  muscle  prevails  only 
as  long  as  no  nervous  tissue  is  present,  and  that  it  gradually  loses  its 
dominating  influence  in  the  course  of  the  development  of  the  latter. 
Thus,  it  may  be  said  that  the  separation  of  the  adult  heart  from  the 
central  nervous  sj^stem  or  the  destruction  of  its  nervous  elements 
again  permits  this  primitive  property  of  the  cardiac  musculature  to 
assert  itself.  Ai'guments  of  this  kind  are  difficult  to  meet,  because, 
while  an  adequate  proof  of  a  supersedence  or  transfer  of  function  of 
this  kind  is  not  at  hand,  no  perfectly  definite  reasons  can  be  given 
against  this  occurrence.     It  seems  best,  therefore,  to  leave  this  matter 

1  Burrows,  Science,  xxxvi,  1912. 


336  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

in  abeyance,  with  the  understanding,  however,  that  the  evidence  so  far 
submitted  favors  the  myogenic  theory. 

The  Nature  of  the  "Internal"  Stimulus. — Even  if  the  cause  of 
the  heart  l)cat  should  finally  be  localized  either  in  the  nervous  tissue  or 
in  the  muscle  tissue,  the  nature  of  the  exciting  agent  must  still  remain 
doubtful.  It  is  customary  to  evade  this  question  l)y  saying  that  the 
cardiac  muscle  possesses  the  power  of  automaticity,  the  implication 
contained  in  this  statement  being  that  this  tissue  embraces  certain 
excitatory  agents  which  are  capable  of  acting  independently  of  outside 
influences.  Strictly  speaking,  however,  this  cannot  be  true,  because 
all  reactions  of  living  substance  are  dependent  upon  material  brought 
to  it  from  the  outside.     Without  stimuli  of  this  kind  life  is  impossible. 

In  seeking  to  discover  the  nature  of  the  "inner"  stimulus,  it  is 
fair  to  assume  that  the  cardiac  contractions  result  in  consequence  of 
an  interaction  between  the  chemical  constituents  of  the  blood  and  those 
of  the  substance  of  the  heart.  If  this  problem  is  restricted  in  this 
way,  further  advance  in  this  direction  necessitates  the  determination 
of  those  substances  which  act  as  exciting  agents  either  individually 
or  when  combined  with  others.  In  what  measure  we  have  succeeded 
in  isolating  these  agents  will  be  brought  out  in  the  succeeding 
paragraphs. 

It  is  a  well-known  fact  that  the  hearts  of  the  cold-blooded  animals 
continue  to  beat  for  some  time  after  their  excision,  while  the  hearts  of 
the  warm-blooded  animals  cease  their  activity  very  soon  after  the 
interruption  of  the  circulation.  Both  types  of  organs,  however,  may 
be  kept  in  an  active  condition  outside  the  body  by  supplying  them 
with  defibrinated  blood  or  some  other  nutritive  fluid.  This  difference 
in  their  behavior  may  best  be  explained  upon  the  basis  of  metabolism. 
As  the  mammalian  heart  possesses  a  more  vivid  metabolism,  it  requires 
a  more  constant  supply  of  nutritive  material,  and  especially,  because 
its  storative  power  is  altogether  too  slight  in  comparison  with  the  work 
demanded  of  it.  It  is  essential,  therefore,  that  it  be  in  possession  of 
an  extensive  coronary  system  which  enables  even  its  most  remote  cellu- 
lar constituents  to  obtain  fresh  substances  in  a  very  brief  time.  The 
heart  of  the  lower  animals,  on  the  other  hand,  does  not  require  a  sys- 
tem of  local  blood-vessels,  because  its  metabolic  processes  are  less  in- 
tense and  are  amply  safeguarded  by  direct  interchanges  with  the  blood 
as  it  traverses  its  cavities.  The  cells  of  the  lower  hearts  also  seem  to 
be  able  to  store  a  considerable  portion  of  their  nutritive  material,  so 
that  it  may  be  made  use  of  whenever  the  blood  supply  is  cut  off. 

It  has  been  found  by  Merunovvicz  that  an  aqueous  extract  of  the  ash  of  the 
blood  exerts  a  stimulating  action  upon  cardiac  muscle.  In  continuation  of  these 
experiments  Ringer'  has  proven  in  1882  that  certain  inorganic  salts,  namely  the 
chlorids  of  sodium,  calcium  and  potassium,  affect  this  tissue  in  a  very  specific 
manner,  because  they  are  especially  adapted  for  maintaining  the  beat.  In  the  case  of 
the  heart  of  the  frog,  these  salts  act  most  efficiently  in  the  following  concentration: 

1  Jour,  of  Physiol,  iv,  1883,  222. 


THE    ORIGIN    OF    THE    HEART    BEAT  337 

NaCl 0 .  65  per  cent. 

KCl 0 . 0:5  per  cont. 

CaClj 0 .  25  per  cent. 

Even  the  nianinialiun  heart  may  lie  kept  lieatinR  for  many  hours  by  perfusing  it 
with  this  sohition.  The  best  results,  howevc'r,  are  obtained  if  the  solution  is  first 
charged  with  oxygen  before  it  is  allowed  to  enter  the  coronary  vessels.  Locke^ 
recommends  a  perfusion  fluid  containing  0.0  per  cent,  of  NaCl,  0.024  per  cent,  of 
CaCls,  0.042  per  cent,  of  KCl,  0.01-0.03  per  cent,  of  NaHCOs,  and  0.1  per  cent, 
of  dextrose.  This  fluid  should  be  warmed  to  35°  C.  and  charged  with  oxygen. 
The  dextrose  is  said  to  prolong  the  period  of  contraction  and  to  renew  the  vigor 
of  those  hearts  which  have  ceased  to  beat  while  still  being  perfused  with  the  pure 
solutions  of  the  aforesaid  salts.  With  the  aid  of  this  solution,  Locke  and  Rosen- 
heim- have  succeeded  in  reviving  the  isolated  heart  of  a  rabbit  on  four  consecutive 
days,  keeping  it  in  activity  each  time  for  several  hours.  In  a  similar  way,  Kuli- 
abivo'  has  been  able  to  incite  contractions  in  a  rabbit's  heart  three  and  four  days 
after  its  removal  from  the  body.  Hering*  revived  the  heart  of  a  monkey  28  and  54 
hours  after  the  death  of  the  animal.  Very  similar  results  have  been  obtained  with 
human  hearts. 


I 


Fig.  175. — -Tracing  of  Contractions  of  a  Frog's  Heart,  Showing  Effect  of 
Adding  a  Trace  of  CaCl2  to  the  NaCl  Solution  Used  Previously  for  Perfusion. 
(Ringer.) 

It  is  evident,  therefore,  that  these  salts  give  rise  to  an  osmotic  environment 
which  is  well  adapted  for  cardiac  muscle.  The  action  possessed  by  each  salt 
individually,  has  been  brought  out  by  the  work  of  Kronecker,^  Howell,''  Loeb^ 
and  others.  By  making  use  of  strips  of  the  ventricle  of  the  frog  or  turtle,  it  has 
been  shown  that  the  preceding  solution  is  capable  of  inciting  a  rhythmic  activity 
which  may  last  for  many  hours.  The  same  end  may  be  attained  by  immersing 
these  preparations  in  a  0.7  per  cent,  solution  of  sodium  chlorid.  The  contractions 
appear  as  a  rule  after  a  latent  period  lasting  from  5-20  minutes,  and  attain  a 
maximal  height  and  length  in  the  course  of  a  few  minutes.  It  is  to  be  noted, 
however,  that  while  this  salt  excites  the  contractions,  it  does  not  maintain  the 
beats  for  any  considerable  length  of  time.  The  muscle  presently  ceases  its  activity 
in  the  state  of  relaxation.  The  sodium  salt,  therefore,  favors  contractility  and 
irritability.  If  a  small  quantity  of  a  solution  of  calcium  chlorid  is  now  added 
to  the  former  in  slight  excess  of  the  sodium,  the  strip  of  muscle  again  begins  to 
contract.  Later  on.  however,  its  contractions  become  more  and  more  forced  until 
it  remains  in  a  condition  of  tonic  shortening,  known  as  calcium  rigor.  By  the 
addition  of  a  small  amount  of  potassium  chlorid,  this  strip  may  then  be  activated 
again.  An  excess  of  potassium,  however,  leads  to  a  slowing  and  a  possible  cessa- 
tion of  the  contractions.  The  muscle  is  then  retained  in  a  state  of  extreme 
relaxation. 

1  Jour,  of  Physiol,  xviii,  1895,  332;  also  see:  Mines,  Ibid.,  xxxvii,  1908,  408, 
and  xlii,  1911,  251. 

2  Ibid.,  xxxvi,  1907,  205. 

3  Pfltiger's  Archiv,  xcvii,  1903,  539. 
*  Ibid.,  cxvi.  1907,  143. 

6  Festschr.  fiir  C.  Ludwig,  1874. 
« .\m.  Jour,  of  Physiol.,  ii,  1898,  47. 
">  Festschr.  fiir  Fick,  1899. 
22 


338  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

While  the  sodium,  calcium,  and  potassium  may  not  be  the  only  agents  con- 
cerned in  this  excitation,  it  must  be  evident  that  they  play  a  most  important  part 
in  the  formation  of  a  molecular  concentration  of  the  blood  which  favors  the 
activity  of  cardiac  tissue.  It  must  also  be  apparent  that  these  salts  are  specific 
in  their  action.  The  sodium,  for  example,  stimulates  contraction,  while  the 
calcium  maintains  the  tonus  and  the  potassium  favors  relaxation.  Obviously, 
therefore,  a  proper  activity  of  the  heart  can  only  be  secured  by  means  of  a  solution 
which  contains  these  salts  in  perfectly  definite  proportions.  Howell,  in  fact, 
believes  that  the  states  of  contraction  and  relaxation  of  cardiac  muscle  are  depend- 
ent upon  an  alternate  and  opposing  interaction  of  these  substances  with  the 
contractile  elements  of  this  tissue.     In  this  connection,  it  is  of  interest  to  note 


Fig.  176. — A  Frog's  Heart  Poisoned  by  Excess  of  Calcium  Salts,  Recovers 
Its  Spontaneous  RaYTHii  on  Adding  a  trace  of  KCl  to  the  Perfusion  Fluid. 
(Ringer.) 

that  Biedermann'  and  Loeb  have  succeeded  in  eliciting  rhythmic  contractions 
in  striated  muscle  by  subjecting  it  to  the  influence  of  isotonic  solutions  of  sodium 
and  lithium.  Solutions  of  calcium,  on  the  other  hand,  have  been  proved  to 
possess  an  inhibitor  action. 

As  far  as  the  nature  of  the  "inner  stimulus"  of  the  heart  is  con- 
cerned, it  may  be  held  that  the  substances  just  enumerated,  actually 
constitute  the  exciting  agent  (Howell),  or  that  they  merely  furnish  a 
medium  in  which  the  true  stimulus  is  then  capable  of  unfolding  its  action 
(Engelmann).  If  the  latter  view  is  adhered  to,  the  stimulating  agent, 
whether  it  be  chemical,  electrical,  or  enzymotic  in  its  nature,  has  not 
been  discovered  as  yet. 


CHAPTER  XXIX 

THE  PHYSIOLOGICAL  PROPERTIES  OF  CARDIAC 

MUSCLE 

Refractory  Period.  Extrasystole. — The  heart  of  the  lower  animals 
may  be  made  to  register  its  contractions  upon  the  paper  of  a  kymo- 
graph by  connecting  its  apex  with  the  free  end  of  a  writing  lever.  A 
thread  and  small  hook  are  used  to  make  this  connection.  Another 
procedure  is  to  place  a  dehcate  rod  upon  the  ventricle  and  to  permit  it 
to  act  against  the  long  arm  of  a  writing  lever.  The  lower  end  of  this 
rod  should  be  equipped  with  a  cup-shaped  platelet  serving  to  retain 
the  former  more  firmly  upon  the  surface  of  the  heart.  A  third  method 
1  Wiener  Sitzungsber.,  Ixxxii,  1880. 


PHYSIOLOGICAL    IMtOPERTIES    OF    CARDIAC    MUSCLE 


339 


consists  in  fastening  the  apex  of  the  ventricle  to  the  long  arm  of  a 
wi'iting  lever,  which  is  pulled  upward  beyond  its  horizontal  position 
by  a  counter  spring  (Fig.  177).  In  the  latter  case,  the  contracting 
ventricle  pulls  the  lever  downward,  while  in  the  first  two  instances  the 
lever  moves  upward  during  systole  and  downward  during  diastole. 

Under  normal  conditions,  the  successive  up  and  down  strokes  are 
of  equal  size,  but  assume  a  smaller  amplitude  as  soon  as  the  prepara- 


FiG.  177. — Schema  to  Illustrate  the  Methods  of  Recording  the  Contractions  of 

THE  Frog's  Heart. 
The  writing  lever  (W)  is  pulled  upward  by  a  spring  (S)  against  the  action   of  the 
heart. 

tion  becomes  fatigued  or  when  it  is  made  to  act  under  less  favorable 
circumstances  (Fig.  178).  Very  similar  records  may  be  obtained  with 
apex-preparations  subjected  to  electrical  stimuli  or  with  strips  of 
ventricular  muscle  tissue  immersed  in  a  solution  of  the  inorganic  salts. 
It  is  to  be  noted,  however,  that  the  amplitude  of  the  contractions  can- 
not be  changed  by  varying  the  strength  of  the  stimuli.     This  fact 


Fig.  178. — Record  of  the  Contractions  of  the  Frog's  Heart. 
The  time  is  registered  in  seconds. 

implies  that  a  heart  always  contracts  with  full  vigor  irrespective  of 
the  character  of  the  stimulation.  This  result  is  somewhat  different 
from  that  ordinarily  obtained  with  striated  and  non-striated  muscle, 
because  the  reactions  of  these  tissues  are  directly  proportional  to  the 
strength  of  the  stimuh.  Cardiac  muscle,  therefore,  is  said  to  behave  in 
accordance  with  the  "all  or  none"  law,  i.e.,  it  always  reacts  maximally, 
whether  the  stimulus  be  slight  or  strong. 


340  PECULIAEITIES    OF    THE    CAHDIAC    MUSCLE    TISSUE 

In  explanation  of  this  phenomenon,  it  should  be  mentioned  that 
Gotch  and  K.  Lucas^  have  shown  that  the  amplitude  of  the  contrac- 
tions of  striated  muscle  is  determined  by  the  number  of  fibers  actually 
involved  in  this  process.  In  other  words,  while  a  slight  stimulus 
activates  only  a  relativel}'  small  portion  of  the  total  mass  of  the  muscle, 
a  strong  stimulus  causes  a  much  more  general  reaction.  The  cellular 
components  of  heart  muscle,  however,  are  not  functionally  independent 
of  one  another,  and  hence,  are  not  adapted  to  give  graded  reactions. 
Thus,  even  the  slightest  stimulus  must  produce  a  wave  of  excitation 
which  spreads  far  and  wide  through  its  different  rows  of  cells  and 
involves  even  its  most  distant  constituents.  This  explanation  of  the 
''all  or  none"  law  permits  of  the  conclusion  that  the  mode  of  contrac- 
tion of  cardiac  muscle  is  not  at  variance  with  that  of  other  contractile 
tissues.  It  must  be  evident,  therefore,  that  the  functional  difference 
to  which  attention  has  just  been  called,  is  dependent  upon  the  number 
of  the  cellular  units  involved  and  not  upon  any  chemicophysical 
differences  in  the  muscle  substance.  Consequently,  the  all  or  none 
law  merely  sei^ves  to  show  that  the  different  components  of  cardiac 
muscle  are  more  closely  allied  with  one  another  than  those  of  skeletal 
muscle.  It  is  easily  noted,  however,  that  this  continuity  is  not  the 
same  in  all  hearts,  as  is  shown  by  the  fact  that  the  effects  in  those  of 
the  frog,  tm'tle  and  different  mammals  always  possess  a  disseminating 
character,  while  those  obtained  in  the  crustacean  heart  do  not. 
Regarded  from  the  standpoint  of  hemodynamics,-  a  maximally  contract- 
ing heart  is  of  course  to  be  preferred,  because  it  gives  rise  to  more 
uniform  discharges  and  more  constant  pressures. 

The  assumption  that  cardiac  muscle  is  a  functional  curiosity,  is 
disproved  fm'ther  by  the  fact  that  it  gives  rise  to  the  phenomena  of 
sumviation  of  stimuli  and  summation  of  contractions,  both  of  w^hich  are 
conspicuous  characteristics  of  skeletal  muscle.  Thus,  it  has  been 
found  that  if  several  subminimal  shocks  are  sent  into  a  quiescent 
strip  of  frog's  ventricle  in  rapid  succession,  these  individual  stimuH 
are  added  to  one  another  until  they  finally  give  rise  to  a  contraction. 
Furthermore,  if  the  ventricle  of  a  Stannius-heart  is  stimulated  with 
single  shocks  at  the  rate  of  one  in  every  ten  seconds,  the  first  reactions 
frequently  tend  to  be  somewhat  smaller  than  those  obtained  later  on, 
so  that  an  ascending  series  is  produced,  resembling  the  "staircase 
contractions"  of  striated  muscle.  This  result  is  obtained  only  under 
experimental  conditions  and,  hence,  does  not  run  counter  to  the  "all 
or  none"  law. 

In  accordance  with  the  well-established  fact,  that  a  mf,NS  of  living 
substance  caimot  continue  to  react  unless  a  sufficient  time  be  allowed 
it  during  which  to  replenish  the  material  destroyed  during  its  pre- 
ceding period  of  activity,  it  may  justly  be  assumed  that  the 
successive  sj^stolic  and  diastolic  phases  of  the  heart  represent  period- 

1  Jour,  of  Physiol.,  xxxviii,  1909,  113. 

2  Woodworth,  Am.  Jour,  of  Physiol.,  viii,  1902,  213. 


PHYSIOLOGICAL    PROPERTIES    OF    CARDIAC    MUSCLE  341 

ically  recuninp;  oataholic  and  anal)olio  pluMiomcna.  No  doubt,  the 
systolic  movements  necessitate  tiie  utilization  of  the  largest  store  of 
its  energy-yielding  material  which  must  first  be  replaced  before  the 
next  contraction  can  take  place.  The  systole,  therefore,  must  be  con- 
sidered as  the  period  of  decomposition  of  the  contractile  substance  and 
the  diastole  as  the  period  of  assimilation.  Moreover,  as  the  irritability 
of  all  tissues  depends  upon  a  proper  store  of  energy-yielding  substances, 
the  power  of  cardiac  muscle  to  respond  to  stimuli  must  be  at  a  mini- 
mum when  catal)olic  processes  are  going  on.  This  is  the  case  during 
systole.  The  stimulus  to  contract  is  given  immediately  preceding  this 
period.  This  implies  that  certain  chemicophysical  changes  result  at 
this  moment  which  eventually  give  rise  to  the  visible  contraction. 
During  systole,  however,  while  the  heart  is  thus  engaged  in  converting 
practically  all  its  potential  energy  into  kinetic  energy,  no  other  exci- 
tation can  be  brought  to  bear  upon  it  effectively.  This  means  that  it 
is  then  in  a  non-responsive  state  and  is,  so  to  speak,  impermeable  or 
refractory  to  outside  influences.  Immediately  upon  the  completion  of 
its  refractory  'period,  it  again  becomes  receptive  and  more  so  later  on 
in  the  course  of  diastole.  Its  greatest  irritability  it  attains  just  before 
the  next  contraction. 

These  changes  in  irritability  may  be  detected  very  easily  if  single  in- 
duction shocks  are  passed  through  the  heart  of  p,  frog  or  turtle  at  any 
time  while  it  registers  its  contractions  upon  the  paper  of  a  kymograph.  ^ 
It  will  be  noticed  that  a  stimulus  which  reaches  it  during  its  systolic 
state,  does  not  alter  the  sequence  nor  the  general  character  of  its  con- 
tractions, whereas  a  stimulus  which  enters  at  the  very  beginning  or  at 
any  time  during  the  diastohc  period  is  followed  by  an  extrasystole. 
This  extra  contraction,  however,  does  not  appear  until  the  succeeding 
normal  one  has  been  completed.  In  accordance  with  what  has  just 
been  said,  it  must  be  clear  that  a  greater  strength  of  stimulus  is  re- 
quired to  produce  this  second  reaction  when  applied  at  the  beginning 
of  the  period  of  relaxation  than  when  apphed  near  its  end.  This  dif- 
ference, as  we  have  just  .seen,  is  accounted  for  by  the  fact  that  the 
restoration  of  the  contractile  substances  has  been  practically  completed 
at  the  end  of  diastole.  The  height  of  these  extrasystoles  corresponds 
very  closely  to  that  of  the  normal  contractions. 

After  the  completion  of  an  extrasystole,  the  heart  most  generally 
remains  in  a  condition  of  relaxation  during  the  interim  of  one  beat.  It 
then  exhibits  a  so-called  compensatory  pause.  This  designation,  how- 
ever, is  not  especially  pertinent,  because  this  temporary  inhibition  does 
not  serve  the  purpose  of  compensating  for  the  preceding  hyper-effort, 
but  only  to  correct  the  disturljance  in  the  rhythm.  The  correctness 
of  this  statement  may  be  proved  without  much  trouble  by  studjdng 
these  extra  contractions  when  generated  in  an  isolated  ventricle. 
If  this  portion  of  the  heart,  or  a  strip  thereof,  is  activated  by  subjecting 
it  to  the  stimulating  influence  of  a  solution  of  the  inorganic  salts,  these 
1  Marey,  Trav.  du  laboratoire,  1876. 


342  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

extra  contractions  may  then  be  incited  without  giving  rise  to  compen- 
satory pauses,  nor  do  we  then  obtain  a  significant  disturbance  of  the 
rhythm.  It  seems,  therefore,  that  this  phenomenon  can  only  develop 
in  the  spontaneously  beating  heart,  the  activity  of  which,  as  we  have 
seen  above,  is  dependent  upon  rhythmic  discharges  from  the  "pace- 
maker" situated  at  the  venous  vestibule.  Under  normal  conditions, 
these  stimuli  are  generated  at  regular  intervals  and  activate  the  auricles 
and  ventricles  in  quick  succession.     The  latter  in  particular  are  well 


Fig.  179. — Tracings  of  Spontaneous  Contractions  of  Frog's  Ventricle,   to  Show 

Refractory  Period. 
In  each  series  the  surface  of  the  ventricle  was  stimulated  by  an  induction  shock  at  e, 
as  indicated  by  the  tracing  of  the  .signal.  In  1,  2  and  .3  this  stimulus  had  absolutely  no 
effect,  since  it  fell  during  the  refractory  period.  In  4,  5,  6,  7  the  effect  of  the  shock  was 
to  interpolate  an  extra  contraction  in  the  .series,  the  latent  period  (shaded  part)  gradually 
diminishing  from  4  to  7  (diastolic  ri.se  of  irritability).  In  8  the  irritability  of  the  prepa- 
ration was  already  considerable,  and  the  latent  period  inappreciable.  The  "  compensa- 
tory pause  "  after  the  extra  beat  is  also  well  shown  in  4,  5,  6,  7,  8.     (Marey.) 

supplied  with  contractile  substances,  and  are  therefore  very  irritable 
and  responsive.  If  they  are  now  made  to  give  an  extrasystole,  the 
subsequent  normal  wave  of  excitation  must  arrive  in  them  at  a  time 
when  they  are  just  engaged  in  producing  this  contraction.  Conse- 
quently, they  are  impermeable  to  this  stimulus  and  refractory.  Inas- 
much as  this  excitation  remains  without  results,  the  ventricles  continue 
inactive  during  the  period  ordinarily  occupied  by  the  next  normal 
contraction.     The  succeeding  normal  wave  of  irritability,  however, 


PHYSIOLOGICAL    PROPERTIES    OF    CARDIAC    MUSCLE 


343 


finds  tho  vditriclc  again  in  :i  receptive  st;it(;  and  is  therefore  able  to 
incite  a  contraction.  No  further  (Hsturbance  takes  place  until  another 
extrasystole  is  interposed. 

The  refractors'  period  and  compensatory  pause  serve  as  a  protective 
mechanism  which  prevents  any  interference  with  the  cardiac  rhythm. 
But  if  such  a  condition  has  actually  arisen  (arhythmia),  their  tendency 
will  be  to  reestablish  normal  relationships  as  quickly  as  possible.  In 
addition,  the  refractory  period  serves  to  check  off  the  individual 
discharges  of  the  "pace-maker"  and  to  regulate  the  length  of  the 
successive  systoles.  Under  ordinaiy  conditions,  therefore,  the  latter 
must  retain  a  twitch-like  character  and  cannot  become  tetanic.  It  is 
possible,  however,  to  prolong  them  unduly  either  by  stimulating  the 
heart  with  a  series  of  strong  induction  shocks,  or  by  exposing  it  to 
heat. 


Fig.  180. — Electrocardiogram  Showing  an   fefxRASYSTOLE  at  e.  and  Compensatort 
Pause  at  c.     (Cunningham.) 


Extrasj'stoles  are  frequently  encountered  in  the  human  heart 
without  being  able  to  recognize  a  distinct  lesion  of  the  myocardimn  or 
of  the  conducting  paths.  No  special  importance  need  be  attached  to 
them  as  long  as  they  remain  infrequent.  Most  commonly  they  find 
their  origin  in  a  hyperirritability  of  the  local  or  general  nervous  ele- 
ments. Two  types  of  extrasystoles  are  recognized  clinically,  namely, 
those  which  are  followed  by  a  distinct  compensatory  pause  and  those 
which  are  not.  The  former  are  more  common  and  are  often  designated 
as  premature  beats.  They  result  in  consequence  of  impulses  which 
start  either  in  the  pace-maker  itself  or  high  up  in  the  conducting  paths 
and  adjoining  auricular  tissue.  The  latter  are  generally  called  inter- 
polated systoles,  and  seem  to  be  due  to  stimuli  which  originate  either  in 
the  substance  of  the  ventricles  or  in  the  more  distal  segment  of  the 
conducting  bundle.  For  this  reason,  they  cannot  seriously  interfere 
with  the  regular  waves  of  excitation  conveyed  downward  from  the 
auricle  and,  hence,  cannot  give  rise  to  a  distinct  compensatory  pause  or 


344  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

a  disturbance  of  the  rhythm.  It  might  also  be  mentioned  that  a  large 
number  of  the  so-called  "premature"  beats  are  caused  by  impulses 
which  arise  in  a  hypersensitive  auricular  tissue.  Whether  these  stimuli 
originate  in  this  particular  area  or  nearer  the  pace-maker,  can  readily 
be  determined  by  noting  the  length  of  time  intervening  between  them 
and  the  next  systole,  because  a  compensatory  pause  must  arise  as  soon 
as  the  distance  between  their  place  of  origin  and  the  ventricle  becomes 
sufficiently  great  to  allow  them  to  reach  the  latter  while  in  systole. 
The  method  of  auscultation  is  not  well  adapted  for  the  detection  of 
these  irregularities  in  rhythm,  and  especially  not  if  they  are  of  the  inter- 
polated type,  but  it  is  possible  to  recognize  them  without  difficulty  with 
the  aid  of  the  electrocardiograph,^ 

The  Tonus  of  Cardiac  Muscle. — The  functional  capacity  of  the 
heart  depends  upon  the  tonus  of  its  muscular  elements.  This  fact 
implies  that  the  latter  are  normally  held  under  a  certain  physiological 
tension,  i.e.,  they  are  retained  in  a  state  intermediate  between  com- 
plete relaxation  and  contraction.  The  tonus,  however,  does  not  re- 
main the  same  for  a  long  period  of  time,  but  varies  with  the  character 
of  the  internal  stimuli.  This  fact  may  readily  be  deduced  from  any 
continuous  record  of  the  beating  heart  of  a  frog,  because  the  curve 
as  a  whole  does  not  follow  along  a  straight  horizontal  line,  but  shows 
long  wave-like  oscillations.  In  this  respect,  cardiac  muscle  does  not 
differ  from  striated  or  non-striated  muscle  tissue,  because  both  of  these 
are  continuously  exposed  to  tonic  impulses  and  are  able  to  relax  fully 
only  if  separated  from  the  central  nervous  system.  It  need  scarcely 
be  emphasized  that  a  muscle  when  held  in  a  position  of  partial  contrac- 
tion, can  yeach  the  condition  of  maximal  shortening  with  much  greater 
rapidity.  This  statement  also  applies  to  the  arteries  and  other  tubular 
organs,  because  their  walls  are  ordinarily  kept  in  a  position  intermedi- 
ate between  constriction  and  dilatation. 

The  property  of  tonicity  of  a  tissue  is  dependent  upon  the  activity 
of  the  nervous  elements  with  which  it  is  connected.  It  is  believed  that 
the  nervous  centers  give  origin  to  a  series  of  subminimal  impulses  which 
tend  to  keep  the  tissue  continually  in  a  condition  of  functional  alertness. 
Concurrently,  it  may  be  reasoned  that  if  these  impulses  are  prevented 
from  reaching  their  destination  for  any  length  of  time,  the  tissue 
loses  its  tonicity  and  eventually  becomes  functionally  useless.  In 
the  case  of  the  isolated  heart,  however,  the  tonus  is  retained  in  a  meas- 
ure, because  its  intrinsic  nervous  elements  are  capable  of  generating 
those  impulses  which  under  normal  conditions  are  derived  from  its 
extrinsic  centers. 

The  nature  of  the  stimuli  upon  which  the  tonus  depends  is  still 
unknown.  It  is  commonly  held  that  the  tonicity  is  due  to  the  same 
stimuli  which  produce  the  contractions.  In  the  former  case,  however, 
they  remain  subminimal,  while  in  the  latter  case  they  become  supra- 

1  Lewis,  Clinical  Disorders  of  the  Heart  Beat,  London,  1913. 


PHYSIOLOCilCAL    PllOPERTIES    OF    CARDIAC    MUSCLE  345 

minimal.  Fano,'  on  the  other  hand,  bohevos  that  thoro  are  two  dif- 
dercnt  kinds  of  excitatory  agents  at  work.  In  support  of  this  conten- 
tion, Gask(^ll  and  Mines-  have  found  that  weak  acids  and  carbon 
dioxid  diminish  the  power  of  contraction  as  well  as  the  tonus,  whereas 
an  increased  alkalinity  gives  rise  to  just  the  opposite  effect.  It  seems 
certain,  however,  that  an  optimum  degree  of  tonus  can  only  be  o})tained 
if  the  body  fluid  possesses  a  perfectly  definite  reaction.  As  the  re- 
action of  the  blood  depends  chiefly  upon  the  tension  of  carbon  dioxid, 
it  may  be  inferred  that  this  gas  plays  a  most  important  part  in  the 
production  of  tonicity.^ 

It  must  be  clear  that  the  tonicity  of  cardiac  muscle  furnishes  a 
means  of  determining  its  functional  capacity.  Under  ordinary  con- 
ditions it  is  sufficient  to  note  the  amplitude  and  force  of  the  contrac- 
tions of  the  exposed  or  isolated  heart,  or  to  measure  the  pressure  which 
the  normally  beating  organ  is  capable  of  developing  in  the  blood-vessels. 
To  begin  with,  the  individual  cells  must  of  course  be  capable  of  entering 
the  state  of  complete  relaxation,  as  well  as  that  of  maximal  contrac- 
tion. Hence,  they  must  possess  a  wide  range  of  movability.  The 
former  quality  is  as  important  as  the  latter,  because  it  determines  the 
capaciousness  or  power  of  fiUing  of  the  entire  organ.  It  must  be 
evident  that  a  loss  of  the  relaxing  power  of  the  muscular  units  must 
place  the  heart  under  a  certain  disadvantage,  because  it  lessens  the 
capacity  of  its  chambers.  Quite  similarly,  it  may  be  said  that  an 
unusual  degree  of  relaxation  must  act  unfavorably,  because  it  tends  to 
invite  an  undue  distention  and  imperfect  emptying  of  the  cardiac 
chambers.  The  latter  condition  indicates  a  loss  of  tonus  approaching 
fatigue,  and  may  lead  to  a  general  dilatation  of  the  organ  when  called 
upon  to  perform  an  extra  amount  of  work.  It  stands  to  reason  that  a 
muscular  unit  which  is  not  tonically  set  is  not  in  a  favorable  position 
to  resist  those  strains  which  frequently  arise  in  the  vascular  system 
in  consequence  of  physical  exertions  and  emotions.  A  loss  of  tonus, 
therefore,  exposes  the  heart  to  the  danger  of  becoming  hyperdistended 
and  dilated. 

Opposed  to  the  condition  of  dilatation  is  the  condition  of  hypertrophy,  which 
presents  itself  in  the  form  of  either  a  deposition  of  perfectly  new  cells  or  an  increase 
in  the  volume  of  those  already  present.  In  either  case,  an  organ  larger  and  heavier 
than  normal  is  the  result.  Hypertrophy  finds  its  origin  in"  the  fact  that  the  cardiac 
cells  are  in  a  tonic  condition  and  react  to  excessive  stimulation  by  increasing 
their  power  of  contraction.  This  change  eventually  prodvices  a  compensatory 
increase  in  the  size  and  massiveness  of  the  heart,  while  the  condition  of  dilatation 
is  a  simple  distention  without  a  deposition  of  new  material.  But  it  is  not  always 
true  that  these  changes  affect  the  organ  as  a  whole,  in  fact,  in  many  instances  only 
single  compartments  are  involved.  Thus,  mitral  stenosis  is  usually  associated 
with  a  hypertrophy  of  the  left  auricle  and  aortic  stenosis  with  a  hypertrophy  of 
the  left  ventricle. 

^  Festschr.  fiir  C.  Ludwig,  Leipzig,  1887. 

2  Jour,  of  Physiol.,  xlvi,  1913,  23. 

^  Patterson,  Piper  and  Starling,  Jour,  of  Physiol.,  xlviii,  1914,  465. 


346  PECULIARITIES    OF    THE    CARDIAC    MUSCLE    TISSUE 

The  abilit}'  of  cardiac  muscle  to  increase  its  substance  is  of  great  dynamical 
importance,  because  in  the  absence  of  this  compensation  grave  circulatory  dis- 
orders would  result.  In  illustration  of  this  statement,  attention  might  briefly  be 
called  to  the  different  lesions  of  the  cardiac  valves,  which  may  persist  for  many 
years  without  serious  impairment  of  the  circulation.  A  stenotic  condition  of  one 
or  the  other  of  the  cardiac  orifices  commonlj'  produces  a  hypertrophic  condition  of 
that  part  of  the  heart  which  forces  the  blood  through  this  opening.  In  this  way, 
the  supply  of  blood  to  the  compartment  situated  distally  to  the  obstruction  may 
be  kept  practically  the  same  for  many  years.  This  is  also  true  in  a  way  of  regur- 
gitation, because  the  continuous  stretching  of  the  cardiac  chamber  by  the  regurgi- 
tating blood  serves  as  a  stimulus  for  its  elements  to  contract  more  forcibly.  In 
both  cases  the  arterial  pressure  and  flow  remain  practically  normal  until  the 
primary  lesion  has  developed  sufRciently  to  exceed  the  limit  of  this  physiological 
compensation. 


SECTION  X 

THE  MECHANICS  OF  THE  CIRCULATION. 

HEMODYNAMICS 


CHAPTER  XXX 
PHYSICAL  CONSIDERATION 

The  Sources  of  Pressure. — If  considered  from  the  kinetic  or  dy- 
namic standpoint,  the  movements  of  fluids  may  be  said  to  be  dependent 
upon  the  force  of  pressure,  which  in  turn  is  derived  from  three  sources, 
namely  from : 

1.  An  outside  factor  (hydraulic  pressure). 

2.  Imparted  motion  (hydrodynamic  pressure). 

3.  The  weight  of  the  fluid  (hydrostatic  pressure). 

In  a  similar  manner  it  may  be  stated  that  the  flow  of  the  blood  finds  its 
cause  in  the  pressure  to  which  it  is  subjected  while  traversing  the 
vascular  channels.  This  force,  as  has  just  been  emphasized,  must  be 
regarded  as  the  product  of  three  factors,  although  it  cannot  be  doubted 
that  in  this  case  the  dynamical  action  of  the  heart  is  the  most  important 
of  the  three. 

Hydratilic  influences  are  brought  to  bear  upon  a  fluid  from  without.  A  con- 
dition of  this  kind  may  be  produced  either  by  permitting  oil  or  mercury  to  press 
upon  water  or  by  subjecting  the  fluid  contents  of  a  syringe  or  of  a  hydraulic  pump 
to  pressure  by  means  of  a  piston.  In  all  these  cases,  the  fluid  must  be  confined  in 
a  closed  receptacle,  or  must  be  kept  under  such  conditions  that  its  chances  of 
escaping  to  the  outside  are  so  slight  that  a  general  displacement  of  it  cannot  result. 
The  vascular  system  fulfills  these  mechanical  requirements  very  efficiently,  because 
its  channels  are  closed  and  are  sufficiently  elastic  to  yield  to  pressure.  The  degree 
of  their  distention,  however,  is  not  sufficiently  great  to  neutralize  the  pressure. 
In  this  case,  the  heart  takes  the  place  of  the  piston  and  the  capillary  bloodbed,  that 
of  the  narrow  outlet.  Hydrodynamic  influences  are  brought  into  play  in  so  far 
as  every  moving  fluid  is  in  possession  of  a  certain  kinetic  energy  which  tends  to 
drive  it  onward,  even  at  a.  time  when  the  external  force  has  ceased  to  act  upon  it. 
At  this  moment,  one  component  of  the  fluid  presses  upon  the  one  ahead  of  it,  and 
so  on,  until  the  end  of  the  column  has  been  reached.  Hydrostatic  influences  are 
also  present,  because  every  fluid  possesses  weight,  and  hence,  its  lower  layers  are 
always  subjected  to  the  pressure  of  its  overlying  strata. 

In  determining  the  degree  of  pressure  exerted  by  these  forces,  the  following 
facts  should  be  kept  in  mind.  The  pressure  of  the  air  restmg  upon  the  surface 
of  the  earth,  amounts  to  about  1  kg.  per  square  cm.  of  area.  This  volume  of  air 
weighs  1033  gm.     This  pressure  which  is  designated  as  one  atmosphere,  may  be 

347 


348     THE   MECHANICS    OF   THE    CIRCULATION,    HEMODYNAMICS 


counterbalanced  by  any  factor  capable  of  exerting  precisely  the  same  degree  of 
pressure.  If  wateris  used  for  this  purpose,  it  would  have  to  be  1033  cm.  in  height, 
provided  its  specific  gravity  is  unity.  If  mercury  Ls  emploj^ed  instead,  a  column 
only  76  cm.  in  height  would  be  required,  because  the  specific  gravity  of  this  element 
is  13.55  times  greater  than  that  of  water.  When  a  pressure  exceeds  that  of  the 
atmosphere,  it  is  rated  as  positive,  and  when  it  is  less  than  the  atmospheric,  as 
negative.  Thus,  the  values  of  the  pressures  prevailing  in  the  different  channels 
and  cavities  of  our  body,  are  always  rated  in  accordance  with  the  line  of  the  atmos- 
pheric pressure  (760  mm.).     This  constitutes  the  zero  line  or  abscissa. 

Dynamically  considered,  blood  behaves  in  much  the  same  way  as  water. 
It  flows  through  the  vascular  channels  in  agreement  with  certain  laws  which  are 
derived  from  those  regulating  the  flow  of  other  practicallj^  incompressible  liquids. 
One  difficulty,  however,  is  met  with  and  that  Ls  the  distensible  and  elastic  char- 
acter of  the  blood-vessels  and  spaces.  For  this  reason,  it  must  be  admitted  that 
the  general  phj'sical  data  given  above,  may  not  be  ap- 
plicable to  the  conditions  encountered  in  a  circulatory 
system  built  up  of  living  matter.  In  spite  of  this  prob- 
ability, however,  it  seems  advisable  to  give  a  brief  dis- 
cussion of  the  factors  controlling  the  flow  of  a  fluid 
through  rigid  tubes,  because  many  of  the  problems  con- 
nected with  the  circulation  of  the  blood  are  founded 
upon  them.  But  as  our  knowledge  regarding  the  dyna- 
mics of  the  movement  of  liquids,  or  hydrodynamics,  is 
still  very  incomplete,  the  present  discussion  must  be  re- 
stricted to  the  simplest  of  the  facts  known. 


Fig.    181. — Diagram 
Illustrating     Tori- 
CELLi's  Theorem. 
h,  height  of  pressure;  R, 
resistance  at  orifice. 


Toricelli's  Theorem  (1643).— If  a  fluid  is 
placed  in  a  receptacle  possessing  vertical  and 
parallel  walls,  it  exerts  a  pressure  upon  the  lower 
surface  of  this  vessel  equal  to  the  weight  of  any- 
other  mass  of  fluid  of  the  same  cross-section  and 
height.  If  a  round  opening  is  now  made  in  the 
bottom  of  this  reservoir,  while  the  quantity  of 
fluid  within  it  is  replenished  sufficiently  to  remain  at  the  level  Qi) ,  the 
fluid  escapes  with  a  velocity  (y)  which  may  be  expressed  by  the  formula : 
V  =  ■\/2gh,  g  being  the  acceleration  produced  by  the  gravity.  It  is  a 
well-known  fact  that  the  speed  attained  by  a  falling  body  equals  2gh, 
and  hence,  the  velocity  of  a  fluid  flowing  through  a  hole  in  the  bottom 
or  side  of  a  receptacle,  is  the  same  as  that  attained  by  the  fluid  when 
falling  in  vacuo  through  the  distance  (/i).  Thus,  it  should  be  possible  to 
determine  with  accuracy  the  volume  of  the  fluid  escaping  in  a  unit  of 
time,  by  contrasting  the  velocity  with  the  cross-section  of  the  outlet. 
It  has  been  shown,  however,  that  the  quantity  of  fluid  which  may  be 
expected  to  escape  upon  theoretical  grounds,  does  not  quite  equal  the 
quantity  obtained.  This  discrepancy  is  caused  by  the  resistance  en- 
countered by  the  fluid  at  the  brim  of  the  orifice  (r) .  As  only  a  limited 
number  of  columns  of  fluid  lie  in  straight  lines  vertically  above  the  open- 
ing, the  others  must  occupy  positions  lateral  to  these.  But  as  the  latter 
tend  to  escape  together  with  the  former,  they  must  converge  toward  the 
center  of  the  orifice,  so  that  a  conical  and  not  a  cylindrical  outline  is 
imparted  to  the  entire  mass  of  outflowing  liquid.  Consequently,  the 
total  energy  (h)  cannot  be  spent  to  produce  velocity,  because  some  of 


PHYSICAL    CONSIDERATION  349 

it  is  required  to  over('oiii(>  the  resistance  at  the  outlet.  Obviously, 
therefore,  the  formula  (h'dueed  bj'-  Toricelli,  holds  true  only  if  the 
resistance  to  tlu>  outflow  is  so  slifz;ht.  that  it  can  justly  be  neglected. 

Flow  of  a  Liquid  Through  Rigid  Tubes. — Further  modifications 
of  the  previous  contention  are  made  necessary  if  the  orifice  of  the 
receptacle  is  (>quipped  with  a  round  tube  of  uniform  diameter,  adjusted 
in  a  horizontal  direction.  It  must  l)e  evident  that  this  addition  places 
an  even  greater  resistance  in  the  path  of  the  escaping  fluid,  thereby 
insuring  a  still  greater  reduction  in  the  outflow.  It  is  essential,  how- 
over,  that  the  size  of  the  tube  do  not  exceed  a  certain  limit,  because, 
if  it  possesses  a  vcuy  large  diameter,  the  conditions  of  flow  become  so 
complicated  that  they  cannot  be  brought  in  accord  with  our  present 
knowledge  pertaining  to  this  matter.  Moreover,  theoretical  specula- 
tions of  this  kind  seem  uncalled  for  at  this  time,  because  channels  of 
exceptional  diameter  are  not  encountered  in  the  vascular  system. 

A  liquid  flowing  through  a  tube,  always  meets  with  a  certain  resistance  which 
is  dependent,  on  the  one  hand,  upon  the  cohesion  of  its  molecules,  and,  on  the 
other,  upon  the  adhesion  of  its  outer  layer  to  the  walls  of  the  vessel.  The  former 
constitutes  the  internal  friction  or  viscosity,  and  the  latter,  the  external  friction. 
Provided,  therefore,  that  a  liquid  moistens  the  vessel  wall,  an  adhesion  results,  in 
consequence  of  which  its  outermost  layers  become  stationary.  The  molecules 
of  the  layers  of  fluid  situated  next  to  the  outermost,  are  also  retarded  by  cohesion, 
but  they  are  not  stopped  altogether.  The  more  centrally  situated  layers  are 
slowed  in  quite  the  same  manner  until  the  axial  column  is  reached  which,  however, 
is  retarded  least  of  all  and  possesses  therefore  the  greatest  speed  of  flow.  When 
speaking  of  velocity,  we  generally  refer  to  the  average  speed  attained  by  a  liquid 
irrespective  of  the  differences  shown  by  its  various  layers.  Furthermore  when 
dealing  with  straight  tubes  which  impart  a  parallel  motion  to  the  different  particles 
of  the  liquid,  the  general  velocity  of  the  flow  is  only  one-half  as  great  as  that  of 
the  axial  stream.  Obviously,  therefore,  the  pressure  of  the  liquid  in  the  reservoir 
is  constantly  made  use  of  in  overcoming  the  peripheral  resistance  composed 
of  the  forces  of  adhesion  and  cohesion.  Thus,  while  a  part  of  the  static  energy 
produced  by  the  mere  position  of  the  liquid,  is  consumed  in  antagonizing  this 
hindrance  to  the  flow,  the  remainder  is  converted  into  kinetic  energy,  as  evinced 
by  the  escape  of  the  liquid  from  the  tube. 

The  resistance  to  the  flow  is  betrayed  by  the  lateral  or  side  pressure  prevailing 
at  the  diff'erent  points  of  a  system  of  tubes.  Thus,  if  a  number  of  vertical  tubes, 
or  piezometers,  are  connected  in  series  with  the  main  horizontal  channel,  some 
of  the  liquid  escapes  from  here  and  enters  these  branches  to  a  height  corresponding 
to  the  pressure  prevailing  at  these  points.  In  other  words,  the  level  of  the  liquid 
in  these  laterals  is  accurately  adjusted  to  the  peripheral  resistance  encountered  by 
the  liquid  as  it  passes  these  points.  It  must  be  clear  that  the  liquid  exerts  a  certain 
pressure  upon  the  internal  wall  of  the  main  tube  which  is  evenly  distributed  in  all 
directions.  Besides,  if  the  main  channel  is  equipped  with  a  branch,  the  pressure 
prevailing  in  the  former,  is  propagated  outward  through  the  orifice  in  its  wall  in 
strict  agreement  with  the  cross-section  of  the  collateral.  Under  this  condition, 
the  internal  pressure  is  capable  of  supporting  in  the  side-tube  a  column  of  liquid 
of  a  certain  height  or  weight.  By  determining  the  latter  (h),  an  accurate  measure 
is  obtained  of  the  pressure  prevailing  at  the  point  where  the  branch  joins  the  main 
tube.  Furthermore,  since  the  resistance  in  a  tube  of  uniform  diameter  is  pro- 
portional to  its  length,  and  since  the  resistance  still  to  be  overcome  diminishes 
with  the  proximity  of  the  outlet,  the  pressure  must  decrease  gradually  in  a  direc- 
tion from  the  reservoir  to  the  outlet.     For  this  reason,  the  occlusion  of  the  latter 


350     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

is  immediately  followed  by  a  rise  of  the  liquid  all  the  way  to  the  reservoir,  because 
under  this  condition  the  collaterals  are  converted  into  mere  recesses  of  the  main 
vessel. 

It  must  be  clear,  therefore,  that  the  power  furnished  by  the  liquid  in  the 
reservoir  (//)  is  the  downward  pressure  of  its  constituents.  A  large  portion  of  it 
(h)  is  utilized  in  overcoming  the  resistance  and  is  therefore  known  as  the  resistance- 
pressure.  The  remainder  (/i')  constitutes  the  actual  driving  force  and  is  com- 
monly spoken  of  as  velocity-pressure.  The  amount  of  each  may  be  determined 
very  readily  by  joining  the  levels  of  the  liquid  in  the  piezometers  by  a  straight 
line  and  by  extending  this  line  until  it  meets  the  reservoir  (y-^i).  It  should  be 
noted,  however,  that  their  sum  total  is  not  absolutely  equal  to  the  head-pressure 
(H).  This  discrepancy  indicates  that  a  fraction  of  the  latter  (x)  is  used  up  in 
overcoming  the  friction  encountered  by  the  liquid  in  its  passage  through  the 
orifice  of  the  reservoir.  The  initial  energy  {H)  may  also  be  produced  in  other 
ways  than  by  means  of  the  position  or  "head"  of  the  liquid  in  a  reservoir,  for 
example,  by  the  movement  of  a  piston  within  a  cylinder.  But  the  results  remain 
the  same  irrespective  of  the  source  of  the  pressure. 


c 

I          I 

>           i 

I 

i         i 

'           / 

X 

\ 

\. 

^ 

\h 

^" 

^ 

^ 

\. 

^-^, 

1 

^j 

^J 

U 

Fig.   182. — A   Pressure   Vessel,  P,    With   A   Horizontal  Outflow  Tube,  0-n,  into 
Which  Vertical  Tubes  or  Manometers  are  Inserted  (a,  6,  c,  d,  c,  and  /) . 


If  the  tube  attached  to  the  reservoir,  does  not  retain  the  same  diameter  through- 
out, but  changes  from  large  to  small,  or  from  small  to  large,  the  dynamical  con- 
ditions resulting  therefrom  may  readily  be  deduced  from  the  foregoing  data. 
Thus,  if  the  median  portion  is  the  larger,  the  speed  of  flow  is  diminished  in  this 
particular  segment,  because  the  velocity  is  inversely  proportional  to  the  cross- 
section.  Moreover,  in  as  much  as  the  resistance  is  less  here,  the  initial  energy  or 
head-pressure  is  used  up  more  slowly  in  this  section.  Consequently,  the  lateral 
pressure  declines  less  rapidly  here  than  nearer  the  reservoir.  On  entering  the 
third  segment  which  possesses  the  same  diameter  as  the  first,  the  original  velocity 
is  again  established,  while  the  increased  resistance  in  turn  insures  a  more  rapid 
fall  in  pressure. 

If  a  tube  is  now  used,  the  second  segment  of  which  is  narrower  than  the  first 
and  third,  the  speed  of  flow  is  increased  in  the  central  one.  This  implies  that  the 
resistance  is  also  increased,  while  the  head  pressure  is  considerably  diminished. 
This  change  is  clearly  indicated  by  the  fall  in  the  lateral  pressure.  On  reaching  the 
third  section  of  the  tube,  the  velocity  and  resistance  are  decreased  as  is  betrayed 
by  a  less  rapid  fall  in  the  pressure.  In  the  preceding  experiments  the  head- 
pressure  has  always  been  kept  constant  by  making  provision  for  a  steady  influx 
of  water  into  the  reservoir  to  compensate  for  its  outflow.     But  if  the  initial  energy 


PHYSICAL    CONSIDERATION  351 

is  not  exerted  continuously,  tlio  fluid  will  escape  from  the  distant  orifice  of  the 
tube  only  when  a  definite  (luantity  has  l)een  forced  into  its  central  end.  Under  this 
condition,  the  outflow  becomes  intermittent,  although  it  does  not  cease  as  yet 
at  the  very  moment  when  the  pressure  is  discontiimed.  It  la^s  behind,  l)ecause 
its  itdienmt  sluggishness  causes  it  to  escape  with  a  rapidity  which  is  less  than  that 
of  the  influx. 

Flow  of  a  Liquid  Through  Elastic  Tubes. — If  the  rigid  tube  is  dis- 
placed by  one  po.ssessiiifj;  elastic  walls,  a  condition  of  flow  will  be  estab- 
lished in  time  which  is  practically  the  same  as  that  described  pre- 
viously. To  begin  with  the  walls  of  the  tube  move  outward  in  the 
direction  of  the  lateral  pressure  exerted  by  the  liquid,  and  this  disten- 
tion continues  until  the  elastic  power  of  the  walls  exactly  counter- 
balances the  internal  pressure.  At  this  time,  the  elastic  tube  really 
displays  the  same  phenomena  as  those  previously  observed  in  the  rigid 
system,  but  naturally,  only  as  long  as  the  head-pressure  remains  con- 
stant. If  the  latter  is  diminished,  the  vessel  wall  must  first  recoil  to 
adapt  itself  to  the  new  conditions. 

If  the  head-pressure  is  now  permitted  to  act  intermittently,  the  conditions 
of  pressure  and  flow  must  be  the  result  of  the  force  and  frequency  with  which 
the  primary  power  is  applied  and  secondly,  of  the  resistance  which  this  primary- 
power  encounters  in  the  system  of  tubes.  To  begin  with,  let  us  suppose  that  the 
pressure  acts  at  long  intervals  and  that  the  resistance  is  slight.  The  latter  con- 
dition may  be  produced  without  difficulty  by  using  a  short  tube  of  relatively  large 
diameter.  In  this  case,  the  entrance  of  the  fluid  is  associated  with  a  distention 
of  the  walls  of  this  tube  and  a  discharge  from  its  outlet  which  is  greatest  during 
the  period  of  highest  pressure,  and  becomes  less  and  less  as  the  driving  force  is 
diminished.  A  flow  of  this  kind  is  characterized  as  intermittent.  If  the  pressure 
is  now  allowed  to  act  more  frequently,  or  if  the  resistance  is  heightened,  or 
both,  the  outflow  becomes  smaller  during  the  interims,  but  does  not  cease  altogether. 
The  flow  is  then  said  to  be  remittent.  By  continuing  to  increase  the  force  and 
frequency  of  the  pressure,  as  well  as  the  resistance,  a  point  will  finally  be  reached 
when  the  outflow  ceases  to  fluctuate.      It  is  then  constant  in  its  character. 

If  a  certain  quantity  of  liquid  is  permitted  to  escape  from  the  reservoir  into  the 
elastic  tube,  the  walls  of  the  latter  are  forced  apart.  The  influx  having  ceased, 
the  walls  tend  to  come  together  again.  This  recoil  is  a  property  of  all  elastic 
bodies.  If  the  pressure  is  now  applied  more  frequently,  while  the  resistance  is 
permitted  to  remain  the  same  or  is  increased,  the  mass  of  the  liquid  in  the  tube 
increases  steadily.  This  is  made  possible  by  the  steady  yielding  of  the  walls  of 
the  tube  in  an  outward  direction.  The  tube  is  distended.  Eventually,  however, 
its  elastic  recoil  effectively  counteracts  all  further  distention  and  storage  of  liquid. 
It  must  be  evident,  therefore,  that  the  quantity  of  fluid  which  is  present  in  the 
tube  in  excess  of  that  constantly  escaping  through  the  outlet,  is  sufficient  to  main- 
tain a  certain  pressure  even  during  the  intervals  of  time  when  the  head  pressure 
is  not  being  exerted.  In  this  way,  the  fluid  is  held  under  a  continuous  pressure 
with  the  result  that  the  outflow  remains  practically  constant.  Thus,  it  will  be 
seen  that  the  property  of  elasticity  by  means  of  which  the  walls  of  the  tube  en- 
deavor to  regain  their  original  position,  is  of  greatest  importance  to  the  agent 
producing  the  pressure,  because  it  helps  to  preserve  normal  conditions  of  flow 
even  during  the  periods  when  the  latter  is  at  rest.  Obviously,  therefore,  the 
energy  developed  by  the  generator  is  stored  each  time  in  the  \valls  of  the  tube 
in  the  form  of  elastic  tension.  It  is  then  spent  during  the  periods  when  the  pri- 
mary force  is  not  acting.  In  this  way,  the  flow  is  kept  constant  in  spite  of  the  fact 
that  a  new  supply  of  fluid  is  had  only  every  now  and  then. 


352     THE    MECHANICS    OF   THE    CIRCULATION,    HEMODYNAMICS 

Analogous  Features  of  the  Circulation  of  the  Blood. — Essentially 
the  same  conditions  prevail  in  the  vascular  system.  The  heart  which 
here  assumes  the  function  of  the  rhythmicallj'  discharging  reservoir 
or  piston  pump,  contracts  and  forces  a  certain  quantity  of  blood  into 
the  vascular  channels.  The  frequency  of  this  organ,  as  well  as  the 
peripheral  resistance,  is  adjusted  in  such  a  way  that  the  blood-vessels 
are  constantly  retained  in  a  condition  of  h^^-perfilling,  made  possible 
by  the  elastic  tonicity  of  their  walls.  In  this  way,  the  intermittent 
ventricular  discharge  is  converted  into  a  continuous  flow.  The  power 
of  the  heart  is  transferred  each  time  into  elastic  tension.  The  latter 
acts  while  the  heart  is  at  rest. 


Fig.  183. — Pressure  Vessel  with  Progressps-ely  Branchixg  Tubes  Which  are  Again 
United  into  One  Collecting  Ch.\nxel. 
This    arrangement   illustrates   the   conditions  prevailing   in   the   vascular   system. 
(Brubaker.) 


If  it  were  not  for  the  fact  that  the  diameters  of  the  different  blood- 
vessels vary  considerably,  the  pressure  prevailing  in  the  vascular 
system  would  be  practically  identical  with  that  existing  in  a  system  of 
tubes  such  as  has  been  represented  in  the  preceding  schema.  In 
reality,  however,  the  central  arterial  trunk  or  aorta,  divides  again  and 
again  into  much  smaller  branches  which  eventually  give  rise  to  the 
capillaries.  Beyond  this  point,  these  fine  tubules  constantly  unite 
into  larger  ones  until  the  vense  cavae  and  right  side  of  the  heart 
have  been  reached.  This  multiple  division  brings  it  about  that  the 
total  cross-area  of  the  vascular  system  is  steadily  increased  from  the 
arteries  to  the  capillaries,  while  beyond  these  tubules,  it  is  again  gradu- 
ally diminished.  For  this  reason,  these  conditions  of  pressure  and 
flow  must  closely  resemble  those  described  in  one  of  the  earlier  para- 
graphs dealing  with  the  dynamics  in  tubes  of  varying  diameter.     To 


PHYSICAL   CONSIDERATION 


353 


illustrate,  as  the  cross-si^ction  of  nil  tiie  capillaries  put  topjether  is  larger 
than  that  of  either  the  arteries  or  veins  when  combined  into  single 
tubes,  the  lateral  pressure  as  well  as  the  velocity  of  flow  must  be  much 
less  in  these  tubules  than  in  th(>  latter  channels.  Besides,  as  the  fric- 
tion in  these  exceedingly  fine  tul)ules  is  consitlerable,  they  really  serve 
the  purpose  of  a  resistance  which  is  interposed  at  this  point  of  the  vas- 
cular system  to  retard  the  flow  of  the  blood.  On  account  of  this  hin- 
drance, the  arterial  blood  is  held  back,  thereby  establishing  a  much 
higher  degree  of  pressure  on  the  arterial  side  of  the  capillaries  than 
could  possibly  be  produced  if  the  offlow  were  not  restricted  at  all. 
Furthermore,  as  the  arterioles  are  capable  of  actively  varying  their 
calibre,  this  resistance  may  be  augmented  or  diminished  at  any  time,  so 
that  smaller  or  larger  quantities  of  arterial  blood  may  be  allowed  to 
escape  into  the  capillaries  and  veins. 

These  changes  in  the  peripheral  resistance  may  be  imitated  with  the  help  of  the 
accompanying  schema  (Fig.  184)  by  equipping  the  horizontal  tube  with  a  stopcock 
possessing  the  same  diameter  as  the  main  tube.  If  the  latter  is  widely  open,  the 
pressure  shows  a  gradual  decline  in  the  direction  from  the  reservoir  to  the  outlet. 


Fig. 


184. — A  Stopcock  is  Inserted  at  the  Middle  of  the  Outflow  Tube  in  Illustra- 
tion OF  THE  Resistance  Furnished  by  the  Capillaries. 


Its  partial  closure,  however,  interposes  a  high  resistance,  in  consequence  of  which 
the  fluid  accumulates  between  this  point  and  the  reservoir,  while  it  declines  on 
the  side  toward  the  outlet  (Fig.  184).  Concurrently,  the  lateral  pressure  exhibits 
a  decided  increase  in  the  central  section  of  this  tube,  and  a  fall  in  its  distal  portion. 
In  our  circulatory  system  changes  of  this  kind  are  brought  about  by  the  con- 
traction of  the  smooth  muscle  cells  situated  in  the  walls  of  the  arterioles.  The 
constriction  of  the  lumen  of  these  tubules  increases  the  resistance  placed  in 
the  path  of  the  arterial  blood,  and  prevents  its  free  escape  into  the  capillaries 
and  veins. 

The  influence  which  the  peripheral  resistance  is  capaljle  of  exerting  upon 
the  flow  of  the  blood,  may  be  illustrated  in  a  very  convincing  manner  by  con- 
necting a  piece  of  elastic  band-tubing  with  an  ordinary  valved  syringe.  The 
outlet  of  this  elastic  tube  should  be  diminished  somewhat  by  equipping  it  with  a 
narrow  piece  of  glass  tubing.  If  the  syringe  is  now  dipped  in  water  and  is  com- 
pressed at  frequent  intervals,  the  band-tubing  is  distended  by  each  influx  of 
water,  but  collapses  as  soon  as  this  central  force  ceases  and  allows  all  the  water  to 
escape  through  the  outlet.  The  flow  is  then  intermittent.  If  the  syringe  is  now 
compressed  at  shorter  intervals,  the  tubing  remains  more  fully  distended  and  the 
flow  becomes  remittent  and  finally  constant.     At  this  time  the  entire  stretch  of 

23 


354     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

tubing  is  under  tho  greatest  possible  elastic  tension  and  subjects  the  fluid  within 
to  the  steady  pressure  of  its  recoiling  walls.  Each  compression  of  the  syringe 
increases  the  pressure  sUghtly,  while  during  the  interims  it  is  somewhat  decreased 
owing  to  the  continuous  escape  of  fluid.  It  Is  to  be  emphasized,  however,  that  this 
system  must  always  be  kept  in  a  hyperfilled  condition,  othenvise  the  flow  cannot 
remain  constant. 


Fig.  ISo. — Simple  Schenl\  to  lLLrsTR.\TE  the  F.\ctors  Producixg  a  Coxst.vxt  He.\d  of 
Pressure  in  the  Arterial  System. 
a,  A  sj-ringe  bulb  with  valves,  represeDting  the  heart:  b,  glass  tube  with  fine  point 
representing  a  path  with  resistance  alone,  but  no  extensibility  (the  outflow  is  in  spurts 
synchronous  with  the  strokes  of  the  pump) ;  c,  outflow  with  resistance  and  also  extensible 
and  elastic  walls  represented  by  the  large  rubber  bag,  e;  the  outflow  is  a  steady  stream  due 
to  the  elastic  recoil  of  the  distended  bag,  e.     (Howell.) 


CHAPTER  XXXI 
BLOOD  PRESSURE 


The  Factors  Responsible  for  Blood  pressure. — In  order  to  prove 
that  the  blood  flows  from  the  arteries  into  the  veins  and  thus  completes 
the  circuit  of  the  body,  Har\,'ey  placed  loose  ligatures  upon  an  artery 
and  neighboring  vein  and  raised  them  gently  out  of  the  wound  until 
their  lumina  became  fully  constricted.  It  was  then  found  that  the 
central  end  of  the  arter\-  and  the  distal  end  of  the  vein  were  highly 
distended,  while  their  other  ends  were  collapsed.  If  the  walls  of  the 
distended  segments  were  then  pierced  with  the  point  of  a  needle,  the 
blood  spm'ted  out  in  fine  jets,  but  with  a  much  greater  force  from 
the  artery  than  from  the  vein.  The  same  observation  was  made  during 
capillary  bleeding,  because  the  blood  oozes  from  these  opened  blood- 
vessels in  small  droplets  which  presently  coalesce  to  form  a  sheet-like 
covering  over  the  injured  area.  These  and  other  observations  read- 
ily prove  that  the  blood  is  held  in  the  vascular  system  under  a  certain 
pressure. 

The  term  blood  pressure  is  often  used  to  denote  the  general  pres- 
sure existing  in  the  vascular  system,  while  at  other  times  it  is  intended 
to  indicate  merely  the  pressure  prevailing  in  the  arterial  channels. 
This  ambiguity  mav  easily  be  avoided  by  making  specific  reference  to 


BLOOD    PRESSURE 


355 


either  the  arterial,  capillary  or  venous  pressure,  because  the  blood 
pressure  really  presents  definite  dilTerences  in  accordance  with  the 
three  divisions  of  the  vascular  system. 

The  pressure  to  which  the  circulating  blood  is  subjected  is  the  prod- 
uct of  a  reaction  participated  in  by  four  factors;  namely  by:  (a) 
the  energy  of  the  heart,  (/;)  the  quantity  of  the  circulating  l)lo()d,  (c) 
the  elasticity  of  the  blood-vessels,  and  ((I.)  the  peripheral  resistance. 
Under  ordinary  conditions,  this  pressure  displays  a  certain  constancy, 
and  retains  a  level  considerably  above  zero  throughout  the  circu- 
latory system  with  the  exception  of  the  central  veins.  In  addition 
it  is  to  be  noted  that  it  is  subject  to  cer- 
tain minor  variations  which  are  de- 
pendent chiefly  upon  the  action  of  the 
heart  and  the  respiratory  movements. 
These  details  will  be  brought  out  more 
fully  by  the  subsecjuent  discussion. 

The  Energy  of  the  Heart. — Each 
ventricular  systole  forces  a  definite 
quantity  of  blood  into  the  arteries. 
Assuming  that  the  other  three  factors 
remain  unchanged,  it  may  be  concluded 
that  the  pressure  must  rise  whenever 
a  new  amount  of  blood  is  added  to 
that  already  existing  in  these  channels, 
and  that  the  pressure  must  fall  when- 
ever the  ventricles  enter  the  state  of 
diastole.  This  relationship  implies  that 
the  energy  of  the  heart  must  be  pro- 
portional to  the  ventricular  output  and 
must  embrace  the  following  minor  fac- 
tors : 

(a)  The  volume  of  the  cardiac  out- 
put, 

(b)  The  frequency  with  which  these 
discharges  are  repeated,  and 

(c)  The  force  with  which  the  blood  is  ejected. 

The  first  condition  is  determined  by  the  capaciousness  of  the  cardiac 
chambers,  or  better,  by  the  power  of  filling  of  the  heart,  the  second  by 
the  number  of  the  discharges  occurring  in  a  given  period  of  time,  and 
the  third  by  the  force  with  which  the  emptying  of  the  ventricles  is 
effected.  Right  here  it  should  be  emphasized  that  the  energy  of  the 
heart  which,  as  has  just  been  stated,  is  only  one  of  the  factors  upon  which 
blood  pressure  depends,  is  subject  to  fluctuations,  because  the  condi- 
tions previously  cited,  do  not  always  act  in  unison,  but  may  actually 
counteract  each  other.  Thus,  the  volume  of  the  different  ventricular 
outputs  may  be  increased  owing  to  a  greater  filling  power  or  relaxa- 
bility  of  the  cardiac  musculature,  without  being  associated  with  a  rise 


Fig.  186. — Record  of  Blood- 
pressure  Showing  the  Cardiac  and 
Respiratory  Variations. 

The  time  registered  in  seconds, 
serves  as  the  abscissa. 


356     THE    MECHANICS   OF   THE    CIRCULATION,    HEMODYNAMICS 

in  the  blood  pressure.  The  cause  of  this  discrepancy  most  frequently 
lies  in  a  lessened  rate  of  the  heart.  For  very  similar  reasons  it  cannot 
be  taken  for  granted  that  a  rapid  heart  always  gives  rise  to  a  higher 
blood  pressure,  because  the  filling  power  of  this  organ  may  be  decreased 
in  a  measure  to  compensate  for  the  increase  in  the  frequency.  More- 
over, as  a  diminution  in  the  power  of  contraction  of  the  cardiac  muscle 
must  be  followed  by  a  reduction  in  the  force  of  ejection,  the  blood  pres- 
sure must  fall  even  when  the  frequency  and  the  filling  power  of  the 
heart  remain  practically  unaltered.  And  again,  while  an  increase  in 
the  power  of  contraction  of  the  cardiac  musculature  generally  raises 
the  pressure,  this  result  cannot  be  attained  if  the  frequency  or  the 
filling  power  of  this  organ  is  diminished. 

In  further  illustration  of  these  complex  interactions  between  the 
factors  giving  rise  to  the  energy  of  the  heart,  it  might  be  mentioned  that 
the  stimulation  of  the  vagus  nerve  leads  to  a  fall  in  the  general  blood 
pressure,  because  the  ventricular  outputs  are  either  diminished  in 
number  or  are  stopped  altogether.^  But  if  a  strength  of  current 
is  employed  which  is  just  sufficient  to  cause  a  moderate  reduction  in 
the  cardiac  rate,  the  filling  power  of  the  organ  may  thereby  be  aug- 
mented in  such  a  measure  that  the  blood  pressure  is  enabled  to  retain 
its  former  level.  Quite  similarly,  the  cutting  of  the  vagi  nerves  most 
generally  produces  a  rise  in  blood  pressure,  because  the  removal  of 
the  inhibitory  impulses  permits  the  heart  to  increase  its  frequency, 
so  that  the  number  of  ventricular  outputs  in  a  unit  of  time  becomes 
greater.  But  it  also  happens  at  times  that  this  procedure  produces  no 
augmentation  at  all,  because  a  proper  relaxation  of  the  cardiac  muscle 
cannot  be  effected,  owing  to  the  high  frequency  of  contraction.  Under 
this  condition,  the  heart  is  quite  unable  to  eject  a  greater  quantity 
of  blood.  Similar  compensations  occur  at  times  during  the  stimulation 
of  the  acceleratory  nerves  so  that  the  rises  in  pressure  ordinarily 
resulting  from  this  procedure,  cannot  attain  their  full  development. 
These  variations  are  not  mere  theoretical  possibilities,  but  are  fre- 
quently observed  under  pathological  conditions.  They  have  been 
cited  here  somewhat  at  length,  in  order  that  they  may  be  made  use  of 
in  explaining  some  of  the  peculiar  changes  in  the  blood-pressure  occur- 
ring in  the  course  of  cardiac  diseases. 

It  has  previously  been  stated  that  the  height  of  the  blood  pressure 
most  commonly  bears  a  direct  relationship  to  the  cardiac  energy  as 
expressed  in  terms  of  the  ventricular  output.  This  means  that  an  in- 
crease in  the  latter,  is  followed  by  a  rise  in  the  blood  pressure,  and  vice 
versa.  In  the  second  place,  we  have  seen  that  the  blood  pressure  is  the 
product  of  four  different  factors,  namely,  the  energy  of  the  heart,  the 
total  quantity  of  the  circulating  blood,  the  elasticity  of  the  blood- 
vessels and  the  peripheral  resistance.  In  view  of  this  fact,  the  pre- 
ceding general  rule  should  therefore  be  amplified  to  include  the  provi- 
sion that  the  other  three  factors  must  remain  constant.  If  they  do  not 
1  O.  Frank,  Zeitschr.  fiir  Biologie,  xxiii,  1901,  1. 


BLOOD    PRESSURE  357 

remain  constant,  thoir  influonco  upon  the  cardiac  onorgy  may  be  niu- 
terially  modified  by  the  changes  in  the  other  three  factors.  It  would 
lead  altogether  too  far  to  give  a  complete  analysis  of  these  interactions 
and  hence,  it  must  suffice  to  illustrate  them  with  the  help  of  a  single 
example,  namely  the  relationshij)  existing  between  the  energy  of  the 
heart  and  the  perii)h(M-al  resistance.  It  should  Ix;  stated  first  of  all 
that  the  peripheral  resistance  may  be  increased  or  decreased.  The 
former  change  gives  rise  to  a  lessened  escape  of  arterial  blood  into 
the  capillaries,  and  the  latter  to  a  more  copious  arterial  offlow.  Sup- 
posing now  that  th(>  cardiac  energy  is  agumented,  we  would  expect  to 
obtain  a  rise  in  the  arterial  blood  pressure.  This  result,  however,  may 
be  nullified  by  a  vasodilatation,  i.e.,  by  a  diminution  of  the  peripheral 
resistance  and  a  greater  offlow  of  the  arterial  blood.  In  a  similar 
manner,  it  may  be  reasoned  that  a  lessened  ventricular  discharge 
must  lead  to  a  fall  in  blood  pressure.  But  this  effect  is  not  always 
obtained,  because  the  diminution  in  the  cardiac  output  may  be  com- 
pensated for  by  an  increase  in  the  peripheral  resistance  occasioned 
by  a  vasoconstriction.  The  simultaneous  appearance  of  an  increased 
cardiac  energy  and  peripheral  resistance  would,  of  course,  raise  the 
blood  pressure.  The  opposite  result  would  be  obtained  after  a  simul- 
taneous depression  of  these  two  factors. 

The  Total  Quantity  of  the  Circulating  Blood. — This  factor  bears 
a  direct  relationship  to  the  blood  pressure,  because  different  degrees 
of  pressure  may  be  established  very  readily  by  simply  varying  the 
volume  of  the  blood,  provided,  of  course,  that  the  other  three  factors 
remain  unchanged.  Conditions  of  this  kind  invariably  result  in  the 
course  of  hemorrhages,  and  during  the  infusion  of  isotonic  solutions  and 
the  transfusion  of  blood.  Under  normal  conditions,  the  vascular  sys- 
tem possesses  the  power  of  adapting  itself  very  quickly  to  different 
quantities  of  blood  by  (a)  varying  the  size  of  the  bloodbed,  (6)  forcing 
the  fluid  elements  of  the  blood  into  the  lymphatic  channels,  and  (c) 
transferring  the  lymph  into  the  bloodstream.  Thus,  slight  losses  of 
blood  are  quickly  compensated  for  by  a  vasoconstrictor  reaction  and  a 
transfer  of  lymph  into  the  vascular  channels.  For  this  reason,  a  de- 
cided fall  in  blood  pressure  cannot  develop  under  these  circumstances, 
unless  the  hemorrhage  has  been  sufficiently  severe  to  offset  this  com- 
pensation. A  similar  reaction  takes  place  whenever  the  amount  of  the 
circulating  blood  is  increased.  The  blood-vessels  then  relax,  and  a 
certain  portion  of  the  blood  seeks  the  lymph  spaces.^  These  changes 
are  often  followed  by  an  extra  discharge  of  water  from  the  body  in  the 
excretions.  It  is  true,  however,  that  any  extraordinary  increase  in 
the  amount  of  the  circulating  blood  gives  rise  to  a  more  decided  and 
more  permanent  rise  in  the  pressure.  It  need  scarcely  be  emphasized 
that  these  alterations  frequently  assume  a  local  character  and  remain 

1  Worm-Miiller  (Ber.  der.  sachs.  Gesellsch.  der  Wissensch.,  1873),  Stolnikow 
(Arch,  fiir  Anat.  und  Physiol.,  1886),  and  Johansson  and  Tigerstedt  (Skand. 
Arch,  fur  Physiol.,  ii,  1889). 


358     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

confined  to  particular  divisions  of  the  vascular  system.  These  local 
hyperemias  and  anemias  may  be  neutralized  by  vasomotor  changes  and 
a  transfer  of  the  plasma,  insuring  a  continuance  of  the  normal  circu- 
latory conditions. 

The  Elasticity  of  the  Blood-vessels. — This  factor  betrays  itself  by  a 
distention  of  the  walls  of  the  blood-vessels  whenever  the  pressure 
within  them  rises.  This  elastic  play  is  most  clearly  in  evidence  on  the 
arterial  side  and  particularly  in  the  central  arteries,  where  we  find  the 
largest  number  of  elastic  fibers.  In  the  more  distal  channels,  the 
elastic  tissue  is  gradually  displaced  by  smooth  muscle  cells,  which  ap- 
pear here  chiefly  in  the  form  of  a  thick  layer  arranged  circularly 
around  the  lumen  of  the  vessel.  Some  of  these  cells  are  also  arranged 
in  a  longitudinal  direction  and  in  such  a  way  that  they  form  a  thin 
coat  externally  to  the  circular.  The  peripheral  arteries  and  arterioles, 
therefore,  contain  practically  no  elastic  fibers,  but  are  made  up  of  a 
heavy  layer  of  smooth  muscle  tissue.  This  difference  in  the  structural 
character  of  the  arterial  system  leads  us  to  infer  that  the  elastic 
forces  have  full  sway  centrally,  while  peripherally  the  prevailing  factor 
is  muscular  contraction.  Hence,  the  aorta  may  be  regarded  as  an 
elastic  pouch,  the  walls  of  which  are  forced  outward  with  every  ven- 
tricular output.  Directly  thereafter  a  recoil  sets  in  at  a  moment  when 
the  elastic  power  of  the  arterial  wall  is  capable  of  overcoming  the 
internal  pressure.  This  means  that  they  accomplish  their  work 
during  the  diastolic  interim,  and  constitute  therefore  a  most  important 
aid  to  the  heart,  because  the  power  generated  by  this  organ  during 
each  systole,  is  immediately  stored  in  their  walls  as  elastic  tension  to 
be  made  use  of  during  the  period  of  cardiac  rest.  Inasmuch  as  the 
blood  is  thus  held  under  a  constant  pressure,  the  arteries  serve  the 
same  purpose  as  the  air-bladder  of  a  bag-pipe  from  which  the  air 
may  be  drawn  in  a  continuous  stream. 

The  energy  of  the  heart,  the  quantity  of  the  blood  and  the  periph- 
eral resistance  are  adjusted  in  such  a  way  that  the  arterial  system 
is  constantly  retained  in  a  state  of  hyperfilling.  This  implies  that  the 
escape  of  the  blood  into  the  capillaries  is  regulated  in  such  a  way 
that  it  is  always  exceeded  by  the  ventricular  output.  In  this  way,  a 
definite  head  of  pressure  is  established  which  cannot  be  nullified 
during  the  diastolic  period  of  the  heart.  It  is  true,  however,  that  the 
pressure  is  somewhat  greater  during  the  systolic  inrush  of  blood,  than 
during  the  diastolic  phase  of  gradual  emptying.  The  offlow  must 
necessarily  be  limited,  because  the  peripheral  resistance  and  the 
frequency  of  the  heart  are  so  accurately  balanced  that  more  than 
a  moderate  recoil  of  the  arterial  walls  cannot  result.  Only  in  case 
the  heart  ceases  to  beat  altogether  do  we  obtain  a  complete  collapse 
of  these  channels,  the  blood  then  accumulating  on  the  venous  side 
and  principally  in  the  central  veins  and  right  side  of  the  heart. 
This  is  the  condition  prevailing  after  death. 

The  preceding  statement  leads  us  to  infer  that  the  diastolic  fall 


BLOOD    PRESSURE  359 

in  the  arterial  l^lood  pressure  must  become  the  greater,  the  longer 
the  interval  between  two  successive  ventricular  discharges.  This 
rule,  however,  is  not  infallible,  because  in  many  cases  a  fall  in  pressure 
resulting  from  an  undue  slowness  of  the  heart,  may  be  effectively 
counteracted  by  an  increase  in  the  peripheral  resistance.  A  com- 
pensation of  this  kind  takes  place  very  frequently,  but  naturally,  it 
cannot  overcome  the  dynamical  disturbances  produced  by  an  exces- 
sively infrequent  heart. 

The  elastic  power  of  the  vascular  system  lessens  the  work  of  the 
cardiac  musculature  very  materially,  because  it  insures  a  constancy  of 
flow  without  necessitating  an  extra  expenditure  of  energy  on  the  part 
of  the  heart.  As  each  cardiac  output  is  accommodated  in  the  arteries, 
their  walls  are  forced  outward.  In  this  way,  a  large  part  of  the  work 
of  the  heart  is  converted  into  potential  energy  in  the  form  of  elastic 
tension  which  is  utilized  later  on  during  the  diastolic  interim,  and  hence, 
the  work  of  this  organ  is  actually  distributed  over  more  than  twice 
the  time  actually  consumed  in  its  muscular  contraction.  This  enables 
the  heart  to  obtain  the  rest  required  for  its  anabolism.  The  importance 
of  the  elasticity  is  also  elucidated  by  the  fact  that  a  rigid  vascular 
system  immediately  converts  the  otherwise  constant  flow  into  one 
possessing  remittent  and  intermittent  qualities.  Each  systole  then 
gives  rise  to  a  quick  onrush  of  blood  which  is  soon  followed  by  a  slowing 
and  a  cessation  of  the  flow.  Very  high  and  very  low  pressures  are 
then  obtained  alternately. 

The  property  of  elasticity  is  possessed  in  a  slight  measure  by  all 
types  of  cells  and  not  only  by  those  composing  the  elastic  tissues.  For 
this  reason,  it  cannot  be  said  to  be  wholly  lacking  in  other  segments  of  the 
vascular  system,  although  we  have  just  seen  that  it  becomes  of  greatest 
dynamical  importance  in  the  central  arteries.  The  structure  of  the 
capillaries  is  such  that  varying  quantities  of  arterial  blood  can  readily 
be  accommodated  in  them  by  simply  changing  the  size  of  their  lumen. 
These  perfectly  passive  changes  are  made  possible  by  the  fact  that 
they  are  distensible,  although  their  elastic  power  is  insignificant.  In 
this  connection,  mention  should  also  be  made  of  the  claim  of  Strieker 
and  others,^  that  the  capillary  lining  cells  possess  contractile 
qualities  which  betray  themselves  in  active  variations  of  their 
thickness  at  the  sites  of  the  different  nuclei.  The  evidence  so  far 
presented  in  favor  of  this  view,  does  not  seem  sufficiently  conclu- 
sive to  warrant  further  discussion  of  this  subject.  Somewhat  dif- 
ferent conditions  are  met  with  in  the  veins.  Here  the  elasticity  again 
plays  a  more  important  part,  because  these  channels  are  large  and 
are  structurally  in  a  position  to  oppose  the  pressure  by  a  very  moderate 
recoil.  It  is  to  be  noted  especially,  however,  that  the  size  of  the  venous 
bloodbed  is  very  largely  dependent  upon  the  quantity  of  the  blood 
transferred  to  them  by  the  arteries.  They  themselves  cannot  vary 
their  caliber  in  an  active  way  by  vasomotor  activity. 
1  Berichte,  Akad.  der  Wissensch.,  Wien,  1865. 


360     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 


The  earlj'  determinations  of  the  elasticity  of  the  blood-vessels, 
were  made  upon  excised  segments  which  were  suspended  from  a 
hook  and  loaded  with  different  weights.  In  as  much  as  the  curve 
obtained  by  this  method  resembled  a  hyperbole,  the  conclusion  was 
drawn  that  the  coefficient  of  the  elasticity  does  not  possess  a  constant 
value  but  increases  with  the  distention.  It  seems,  however,  that  the 
degree  of  distensibility  obtained  under  this  condition,  is  not  comparable 
to  the  distensibilitj'  produced  by  an  internal 
pressure,  but  merely  gives  us  an  idea  regarding 
the  compactness  or  strength  of  the  blood- 
vessels. Marey^  sought  to  establish  more 
perfect  experimental  conditions  by  placing  seg- 
ments of  arteries  in  plethysmographs  and  by 
subjecting  their  walls  to  a  stead\^  internal  pres- 
sure. This  end  he  attained  bj'  connecting  the 
lumen  of  the  segment  with  a  bottle  filled  with 
saline  solution  which  he  could  raise  to  a  certain 
level  above  the  preparation.  Roy-  and  others 
state  that  a  steadily  rising  pressure  leads  to  a 
gradual  increase  in  the  cahber  of  the  blood- 
vessel, but  a  hmit  is  soon  reached  bej'ond  which 
the  distention  diminishes  very  rapidly.  In 
rabbits  the  normal  distensibiUty  is  reached  with 
a  pressure  of  70  mm.  Hg,  in  dogs  at  75  to  125 
mm.  Hg,  and  in  the  ox  at  100  to  150  mm.  Hg. 
A  much  higher  pressm'e  is  required  to  cause  a 
-  XT  .',  A  normal  artery  to  rupture.  In  accordance  with 
RAXGEMENT  FOR  TESTING  thc  determinations  of  Grchaut  aud  Quinquaud,' 
THE  El.^tic  Power  of  the  carotid  artery  of  the  dog  can  witlistand  an 
Blood-\-essels.  internal  pressure  of  600  mm.  Hg,  while  the  lowest 

penS  In  Y  gfais'^tX  Pressure  necessary  to  burst  the  carotid  artery  of 
filled  'n-ith  saline  solution  man  amouuts  to  1.29  ni.  Hg.  As  the  smaller 
(T).    Its  ends  are  closed  arteries  are  even  stronger  than  the  larger  ones 

with   discs   of   rubber    and  i  ^  i  ,       •    i  i  j  •  i 

and  as  the  arterial  pressure  seldom  rises  above 
150  mm.  Hg,  the  margin  of  safety  is  more  than 
ample. 

It  is  also  of  interest  to  note  that  the  opti- 
mum degree  of  movability  of  the  vessel  wall  is 
had  at  a  pressure  most  closeh'  approaching  the 
normal.  At  this  time  the  most  perfect  elastic  play  is  obtained.  If  the 
pressure  is  raised  much  beyond  this  point,  the  distensibility  becomes  less 
and  less.  Supposing,  therefore,  that  the  quantity  of  the  circulating 
blood  is  increased,  the  power  of  the  vascular  system  to  accommodate 

1  Trav.  de  Lab.,  iv,  1880,  253. 

-Jour,  of  Physiol.,  iii,  1881.  125;  also  see:  Zwardemaker  (Neterl.  Tijdschr.  vor 
Jencesk.,  xxiv,  1888,  61),  and  Frank  (.\nn.  der  Physik.,  1906). 
5  Jour,  de  I'anat.  et  de  la  Phvsiol.,  xxvi,  1885. 


its  lumen  connected  with 
a  pressure  bulb  (B).  The 
meniscus  of  the  saline  solu- 
tion M  in  tube  C  indicates 
the  degree  of  distention  of 
the  artery. 


BLOOD    PRESSURE  361 

this  extra  amount  of  blood  must  become  the  less,  the  higher  the  pressure! 
already  established.  Concurrently,  it  may  be  reasoned  that  the  energy 
of  the  heart  may  be  most  seriously  impaired  by  forcing  it  to  increavse 
its  activity  at  a  time  when  the  tension  in  the  vascular  system  is  high, 
because  the  vascular  channels  cannot  then  yield  so  readil}''  to  the  internal 
pressure.  The  veins  attain  their  maximal  cubic  distention  at  much 
lower  pressures  than  the  arteri(\s,  and  their  extensibility  is  much  less. 
They  are  more  easily  torn  when  manipulated,  Vjut  are  more  yielding 
than  the  arteries.  This  may  well  be  so,  because  the  pressures  which 
they  arc  called  upon  to  withstand,  scarcely  exceed  20  nun.  Hg  even 
under  pathological  conditions. 

The  Peripheral  Resistance. — This  factor  serves  as  an  expression 
of  the  size  of  the  "blood-gate"  at  the  artcriocapillary  junction.  It 
may  be  inferred  that  the  resistance  placed  in  the  path  of  the  arterial 
blood,  must  become  the  less  the  larger  this  orifice.  The  friction  which 
is  responsible  for  the  production  of  this  resistance,  is  composed  in 
reality  of  two  types  of  frictions  which  may  be  designated  respectively 
as  the  "external"  and  the  "internal."  The  former  is  produced  by  the 
blood  as  a  whole  as  it  rubs  against  the  internal  surface  of  the  vessel 
wall  and  the  latter,  by  the  bumping  together  of  the  different  con- 
stituents of  the  blood.  The  tenn  viscosity  is  usually  applied  to  this 
intennolecular  friction.  It  is  evident  that  the  hindrance  placed  in 
the  path  of  the  arterial  blood,  must  increase  whenever  the  "blood- 
gate"  is  made  smaller  and  decrease  whenever  it  is  made  larger.  In 
the  first  instance,  the  arterial  influx  into  the  capillaries  is  diminLshed, 
and  in  the  second  increased.  Supposing,  therefore,  that  the  other 
three  factors  remain  the  same,  the  first  change  must  lead  to  a  rise  and 
the  second,  to  a  fall  in  the  arterial  pressure. 

Special  emphasis  has  been  placed  upon  the  conditions  existing  at 
the  artcriocapillary  junction,  because  the  distalmost  branches  of  the 
arterial  system  are  equipped  with  especially  powerful  rings  of  smooth 
muscle  cells,  which  enable  them  to  influence  the  blood  stream  most 
decisively.  This  statement,  however,  is  not  meant  to  imply  that  the 
peripheral  resistance  is  formed  in  the  arterioles  and  not  in  the  capil- 
laries. A  detluction  of  this  land  could  not  possibly  be  correct,  because 
it  is  a  well-known  fact  that  no  segment  of  the  vascular  system  pro- 
duces a  greater  amount  of  friction  than  the  capillaries.  This  must  be 
so,  because  the  column  of  blood  is  divided  by  them  into  the  finest 
possible  streams,  many  of  which  are  no  broader  than  the  diameter  of 
a  single  red  cell.  Although  generators  of  the  peripheral  resistance,  it  is 
evident  that  the  capillaries  as  such  are  quite  unable  to  vaiy  this 
resistance,  because  they  are  not  in  possession  of  an  active  means  for 
influencing  the  blood-stream.  This  function  is  relegated  to  the  arter- 
ioles which,  as  we  have  j  ust  seen,  act  as  powerful  sphincters,  permitting 
larger  and  smaller  quantities  of  arterial  blood  to  escape.  Conse- 
quently, the  state  of  filling  of  the  capillaries  is  determined  very  largely 
by  the  arterioles.     In  view  of  their  decided  vasomotor  qualities,  it 


362     THE    MECHANICS    OF   THE    CIRCULATION,    HEMODYNAMICS 

may  also  be  concluded  that  they  are  the  chief  factor  regulating  the 
peripheral  resistance. 

Reference  has  repeatedly  been  made  to  the  close  functional  relation- 
ship existing  between  the  peripheral  resistance  and  the  energy  of  the 
heart.  Thus,  it  has  been  said  that  a  high  blood  pressure  resulting  from 
vasoconstriction,  is  commonly  associated  with  a  decrease  in  the  fre- 
quency^ of  the  heart,  and  vice  versa.  Although  not  wishing  to  over- 
emphasize this  reflex  compensation,  the  foregoing  facts  will  go  far  to 
show  that  the  blood  pressure  is  more  closely  dependent  upon  the  inter- 
action of  the  two  factors  just  mentioned  than  upon  the  quantity  of  the 
circulating  blood  or  the  elasticity  of  the  blood-vessels.  No  doubt,  the 
former  are  subject  to  more  frequent  changes  than  the  latter,  i.e.,  under 
normal  conditions  the  quantity  of  the  blood  and  the  elasticity  remain 
the  same  for  much  longer  periods  of  time. 

THE  DIRECT  AND  INDIRECT  METHODS  OF  RECORDING  BLOOD 

PRESSURE 

Methods  for  Determining  the  Arterial  Blood  Pressure. — The  pro- 
cedures employed  to  ascertain  the  pressures  in  the  different  parts  of  the 


Tn 


Fig.   188. — Diagram   Illustrating  the  Indirect  Method  of   Measitring  Blood- 
pressure. 
A,  arm  surrounded  Viy  a  flat  rubber  pouch,  R;  by  means  of  a  rubber  bulb,  B,  a  pressure 
is  set  up  in  this   system   of  tubing  sufficient  to  compress  the  artery.     This  moment  is 
indicated    by    the    manometer    (M). 

vascular  system,  differ  somewhat  in  accordance  with  the  nature  o 
the  blood-vessel.  If  the  direct  method  is  resorted  to,  the  vascular  chan- 
nel is  opened  and  the  blood  brought  into  immediate  contact  with 
the  recording  instrument.  If,  on  the  other  hand,  the  indirect  method 
is  employed,  the  blood-vessel  is  left  intact,  while  the  pressure  existing 
therein  is  accurately  balanced  by  a  known  pressure  set  up  in  an  arti- 
ficial system  immediately  adjoining  it  (Fig.  188).  Obviously,  there- 
fore, the  direct  procedure  is  applicable  only  to  animals  and  to  blood- 
vessels of  larger  caliber,  whereas  the  indirect  or  bloodless  method 
may  be  practised  upon  animals  as  well  as  upon  man. 

The  first  attempt  to  ascertain  the  pressure  of  the  blood,  was  made 
in  1732  by  the  Rev.  Stephen  Hales,  ^  an  English  clergyman.     A  long 

1  Statical  Essays,  1733. 


BLOOD    PRESSURE 


3('>3 


copper  cannula  was  insortod  in  the  artery  in  the  groin  of  a  horse  whicli 
in  turn  was  connected  with  a  vertical  tube  of  fi;lass,  measuring  nine 
feet  in  height  and  one-sixth  of  an  inch  in  diameter.  On  removing  the 
ligature  from  th(\  artery,  the  blooil  was  seen  to  enter  the  tube  to  a 
height  of  eight  feet  and  three  inches  above  the  level  of  the  left  ventricle. 
However,  it  did  not  rise  to  this  height  at  once,  but  gradually,  and 
finally  exhibited  small  oscillatory  fluctuations. 

This  single  vertical  tiil^e  was  displaced  later  on  by  a  U-shaped  tube,  a  further 
reduction  in  its  length  being  made  possible  by  filling  it  with  mercury,  b(!cause  this 
element  possesses  a  specific  gravity  13.5  greater  than  that  of  water.  Ludwig  finally 
equipped  the  distal  limb  of  the  mercury  column  of  these  manometers  with  a  float 
and  slender  vertical  rod  to  which  he  attached  a  writing  point.  This  arrangement 
enabled  him  to  record  the  excursions  of  the  mercury  upon  the  paper  of  a  kymograph 
(Fig.  149).  In  recent  years  use  has  also  been  made  of  various  types  of  membrane- 
manometers,  in  which  the  intravascular  pressure  is  counter-balanced  by  the  elastic 
force  of  a  rubber  membrane.  The  displacements  of  this  membrane  can  be  accu- 
rately recorded  by  permitting  it  to  act 
against  a  writing  lever,  or  by  permitting  it  to 
reflect  a  beam  of  light  from  a  delicate  mirror 
fastened  to  its  surface. 

For  obvious  reasons  the  direct  method 
can  only  be  applied  to  arteries  and  veins 
which  are  sufficiently  lai^e  to  allow  the  in- 
troduction of  a  cannula.  On  the  arterial 
side,  the  pressure  is  measured  most  con- 
veniently in  the  carotid  and  femoral  arteries, 
the  former  blood-vessel  being  used  most 
frequently,  because  it  is  more  accessible  and 
in  closer  proximity  to  the  center  of  the  cir- 
culatory system.  In  either  case,  it  should 
be  remembered  that  we  are  not  determining 
the  pressure  in  this  particular  vessel,  but  in 
the  one  situated  centrally  to  it.  To  illustrate, 
the  carotid  artery  leaves  the  aorta  almost  at 
right  angles  and  plays,  therefore,  the  same 
role  as  the  free  end  of  a  T-tube,  i.e.,  it  per- 
mits the  pressure  which  is  exerted  in  a  radial 
direction  upon  the  internal  surface  of  the  wall 
of  the  aorta  to  be  propagated  directly  out- 
ward   into  the  manometer    (Fig.    189).     It 

must  be  clear,  therefore,  that  the  pressure  prevailing  in  the  carotid  artery  itself  can 
only  be  ascertained  if  this  vessel  is  connected  with  the  recording  instrument 
either  by  means  of  a  T-tube,  or  by  means  of  a  straight  cannula  inserted  into  one 
of  its  branches.  This  purpose  may  be  served  by  the  arteria  thyroidea,  because 
the  lateral  carotid  pressure  is  propagated  through  this  blood-vessel  directly  into 
the  manometer  (Fig.  189,  II).  In  this  connection  attention  should  also  be  called 
to  the  fact  that  the  distal  stump  of  an  artery  is  not  necessarily  without  pressure, 
because  in  most  cases  anastomoses  are  present  which  permit  at  least  a  slight 
quantity  of  blood  to  enter  this  channel  in  an  indirect  way. 

In  order  to  ascertain  the  venous  pressure,  it  is  necessary  to  insert  a  T-tube, 
the  free  end  of  which  is  connected  either  with  a  U-shaped  manometer  filled  with 
normal  saline  solution,  or  with  a  membrane  manometer  possessing  the  least  possible 
resistance.  The  oscillations  of  the  column  of  saline  solution  may  be  registered 
by  placing  a  bell-shaped  float  and  writing  needle  upon  its  distal  limb.  This  modi- 
fication   in    the  method  of  registration  is  made  necessary  by  the  fact  that  the 


Caret/ d 


La.vo'^M 


/S'rf'i 


n 


Fig.  18  9. — Diagram  to  Show 
THAT  A  Manometer  Connected  with 
THE  Carotid  Artery  Measures  the 
Lateral  Pressure  in  the  Aorta. 


364     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

pressure  throughout  the  venous  system  is  very  low  and  cannot  therefore  support  a 
column  of  mercury  of  adequate  height  nor  deviate  a  membrane  possessing  slight 
elastic  powers.  Furthermore,  the  venous  pressure  cannot  be  measured  by  con- 
necting the  manometer  with  the  peripheral  or  central  end  of  the  vein,  because  the 
blocking  of  the  tlistal  stump  of  the  vein  would  give  rise  to  a  venous  stagnation  which 
would  be  indicative  of  the  pressure  prevailing  in  the  corresponding  arterial  supply 
tubes.  Quite  similarly,  the  use  of  the  central  stump  would  expose  the  manometer 
to  the  pressure  existing  in  the  more  central  vein. 

Having  inserted  a  suitable  cannula  in  the  blood-vessel,  the  entire  tubing 
between  it  and  the  manometer  is  filled  with  a  solution  tending  to  prevent  the 
coagulation  of  the  blood.  A  saturated  solution  of  sodium  carbonate  or  bicar- 
bonate, a  5  per  cent,  solution  of  sodium  citrate  or  a  25  per  cent,  solution  of  mag- 
nesium sulphate  may  be  used  for  this  purpose.  A  device  which  often  saves 
much  time  is  to  connect  the  manometer  with  a  reservoir  containing  one  or  the 
other  of  these  solutions,  so  that  the  connecting  tubes  may  be  flushed  out  when- 
ever they  become  bloiiked  by  coagula.  On  the  venous  side,  a  0.7  per  cent,  solu- 
tion of  sodium  chlorid  should  be  employed,  because  as  the  pressure  encountered 
in  these  channels  is  low,  and  may  even  fall  below  zero,  a  part  of  the  fluid  in  the 
connecting  tube  may  be  drawn  into  the  circulation  and,  unless  non-toxic,  may 
produce  depressive  effects.  In  some  cases  it  may  be  necessary  to  render  the 
blood  as  a  whole  non-coagulable,  which  end  may  be  accomphshed  by  the  injection 
of  a  solution  of  peptone  or  of  an  extract  of  leeches  (hirudin). 

On  removing  the  clamp  previously  placed  upon  the  artery,  the  blood  will 
be  seen  to  enter  the  connecting  tube  and  to  displace  the  column  of  mercury  out- 
ward until  the  weight  of  the  latter  exactly  counterbalances  the  blood  pressure. 
As  soon  as  an  equilibrium  between  these  two  opposing  forces  has  been  established, 
the  mercury  undergoes  a  series  of  rhythmic  fluctuations,  the  smaller  ones  of  which 
are  dependent  upon  the  contractions  of  the  heart  and  the  larger  ones  upon  the 
respiratory  movements.  The  former  are  known  as  the  cardiac  and  the  latter  as 
the  respiratory  variations  in  the  arterial  blood  pressure.  Both  must  be  sharply 
differentiated  from  oscillations  of  a  similar  kind  which  appear  in  the  central  veins 
and  are  designated  as  the  cardiac  and  respiratory  variations  in  venous  pressure. 
Moreover,  if  the  experimental  conditions  are  especially  favorable,  a  third  type  of 
variation  frequently  appears  in  the  arteries  which  is  of  much  longer  duration 
than  the  others  and  is  known  as  the  Traube-Hering  curve.  The  character  and 
cause  of  these  changes  will  be  considered  more  fully  in  a  subsequent  chapter. 

It  has  been  pointed  out  above  that  the  mercury  is  quite  unable  to  follow 
quick  changes  in  pressure  with  accuracy.  On  this  account,  a  membrane  manome- 
ter should  be  used  whenever  it  is  desired  to  depict  the  character  of  the  individual 
pulsations.  A  mercury  manometer,  on  the  other  hand,  should  be  employed  when- 
ever it  is  intended  merely  to  obtain  a  general  picture  of  the  height  of  the  pressure. 
Special  directions  for  the  use  of  these  instruments  have  been  given  previously 
(page  293). 

The  Arterial  Pressure  in  Different  Animals  and  Arteries. — The 

direct  method  has  been  apphed  to  man  in  a  few  isolated  cases,  when 
it  became  necessary  in  the  course  of  operations  to  divide  certain 
peripheral  blood-vessels.  For  the  femoral  and  brachial  arteries^ 
the  average  value  of  120  mm.  Hg  has  been  found  and  for  the  tibial 
the  value  of  80-90  mm.  Hg.  The  pressures  obtained  under  the  most 
favorable  conditions  in  other  animals  have  been  compiled  by  Volkmann 
and  Nikolai  as  follows: 

1  Faivre,  Gazette  mcd.  de  Paris,  1856,  and  Albert,  Med.  Jahrb.,  Wien,  1883. 


BLOOD    PRESSURE  365 

Horse 180  mm.  Hr 

Calf 100  mm.  Hg 

Sheep 1()0  mm.  Hg 

Dog 140  mm.  Hg 

Goat 130  mm.  Hg 

Cat 110  mm.  Hg 

Rabbit 100  mm.  Hg 

Guinea-pig 8.5  mm.  Hg 

As  the  fluctuations  even  among  animals  of  the  same  species  are  very 
considerable,  it  is  not  apparent  that  the  size  of  the  animal  bears  a 
direct  relationship  to  the  pressure.  It  is  also  noted  that  the  pressures 
among  animals  of  different  species  vary  so  widely  that  they  overlap. 
In  spite  of  this  divergency,  however,  there  seems  to  be  a  definite  tendency 
on  the  part  of  animals  of  the  same  group  to  preserve  a  certain  height 
of  blood  pressure.  The  cold-blooded  animals  show  much  lower  values 
than  the  mammals.     The  following  table  may  be  of  interest: 

Cephalopods 25-80  mm.  Hgi 

Fishes  (torpedo) 25  mm.  Hg^ 

Amphibia: 

Grassfrog 29-40  mm.  Hg^ 

Bullfrog 22-26  mm.  Hg« 

Reptilia : 

Crocodile 30-50  mm.  Hg^ 

Turtles 25-35  mm.  Hg^ 

Concerning  the  arterial  pressure  it  may  be  stated  that  it  diminishes 
gradually  in  the  direction  from  the  heart  toward  the  periphery,  but 
the  decrease  is  slight,  because  the  pressure  in  the  distalmost  arteries 
is  only  a  few  millimeters  below  that  prevailing  in  the  aorta.  This  fact 
implies  that  the  blood  does  not  encounter  a  considerable  resistance 
during  its  journey  to  the  arterioles.  Volkmann,  for  example,  found 
the  pressure  in  the  carotid  arteries  of  two  calves  to  be  116.3  and  165.5 
mm.  Hg,  respectively,  while  the  pressure  in  the  metatarsal  arteries 
amounted  as  yet  to  89.3  and  146.0  mm.  Hg.  For  the  dog  Fick^  gives  the 
values  of  176  mm.  Hg  for  the  aorta  and  132  mm.  Hg  for  the  tibial 
artery.  According  to  Burton-Opitz,Hhe  difference  in  pressure  between 
the  femoral  and  hepatic  arteries  of  the  dog  amounts  to  4.4  mm.  Hg, 
and  between  the  former  and  the  more  distal  arteria  gastroduodenalis 
to  10  mm.  Hg.  The  fact  that  the  original  pressure  is  used  up  much 
more  rapidly  in  the  distalmost  branches  of  the  arterial  system  is 
indicated  by  the  observations  of  v.  Frey,^  who  has  furnished  the  fol- 
lowing data: 

1  Fuchs,  Pfluger's  Archiv,  60,  1895,  173. 

2  Schonlein,  Bull,  scient.  de  la  France,  xxvi. 

3  Hofmeister,  Pfluger's  Archiv,  44.  1889. 

"  Burton-Opitz,  Am.  Jour,  of  Physiol.,  vii,  1902,  243. 

6  Edwards,  ibid.,  .xxxiii,  1914,  229. 

«  Festschr.  zur  Iten  Sacularf.  der  Univ.  Wurzburg,  i,  1882. 

^  Pfluger's  Archiv,  cxlvi,  1912,  344. 

^  Festschr.  fur  B.  Schmidt,  Leipzig,  1896. 


366      THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 


Radial  artery  at  wrist 150-160  mm.  Hg 

Radial  artery  at  base  of  thumb 120-130  mm.  Hg 

Radial  artery  at  last  phalanx 100-110  mm.  Hg 

In  this  connection  the  following  determinations  of  the  mean  blood 
pressure  in  dogs,  made  by  Dawson, ^  may  be  of  interest: 

Carotid,    brachocephalic,    superior    mesenteric    and    renal 

arteries 123  mm.  Hg 

Inferior  mesenteric  artery 119  mm.  Hg 

Iliac,  femoral,  saphenous  and  brachial  arteries 118  mm.  Hg 

Arteries  of  the  circle  of  Willis 104  mm.  Hg 

The  Indirect  Method  of  Recording  the  Arterial  Blood  Pressure. 

The  Method  of  Palpation. — The   principle   upon   which    the   indirect 

method  is  based  is  simple,  and  has  really 
been  employed  for  centuries  in  palpating 
the  pulse.  Two  or  three  fingers  are  usually 
used  for  this  purpose,  the  arterj^  being  com- 
pressed with  the  central  finger  until  the 
pulsations  can  no  longer  be  felt  with  the 
more  distal  one.  The  force  required  to 
occlude  the  artery  serves  as  the  measure 
of  the  pressure  existing  within  it. 

The  indirect  method  consists  in  estab- 
lishing a  known  outside  pressure  which  ex- 
acth'  balances  the  pressure  in  the  blood- 
vessel. The  first  instrument  of  this  tj'pe 
was  constructed  bj^  Vierordt-  who  attempted 
to  measure  the  degree  of  pressure  neces- 
sary to  obliterate  an  artery  by  attaching 
a  pelotte  to  the  receiving  leverof  asphj'gmo- 
graph.  A  distinct  advance  was  made  in  1876  by  v.  Basch^  who  employed 
a  glass  tube  which  was  closed  at  one  end  by  a  rubber  membrane  and 
was  then  filled  with  water.  Its  free  end  was  joined  with  a  mercury 
manometer  so  that  the  pressure  required  to  occlude  the  artery  could 
be  accurately  registered.  In  1883,  v.  Basch  advised  the  use  of  a  metal 
capsule  (C)  which  was  closed  bj'  a  rubber  membrane  and  equipped  with 
a  metal  spring  and  indicator  {M).  This  principle  was  subsequently 
made  use  of  in  the  construction  of  the  dynamometer  of  Hill  and 
Bernard*  and  the  sphygmometer  of  Oliver.^  At  about  this  time  the 
experiments  of  ^larey  led  to  the  invention  of  the  plethysmograph,  an 
instrument  which  was  made  use  of  by  him  as  well  as  by  Hiirthle^  and 
Mosso"  for  the  compression  of  the  artery. 

1  Am.  Jour,  of  Physiol.,  xv,  1905,  244. 
^Lehre  vom  Arterienpuls,  1855. 

3  Zeitschr.  fur  klin.  Med.,  ii,  1883,  79. 

*  Jour,  of  Physiol.,  xxiii,  1898,  4. 

'=  Ibid.,  xxii,   1897.  51. 

^  Deutsche  med.  Wochenschr.,  1896. 

'  Zentralbl.  fur  Physiol.,  x,  1896. 


Fig.   190.— Vox  B.\sch 

sphtgmoilvxometer. 
C,  metal  capsule  and  rubber 
pouch  for  occluding  arterj-;  M, 
tonometer  for  registration  of 
pressure  which  is  necessary  to 
occlude  the  arterj'. 


BLOOD    PRESSURE 


367 


A  very  simple  sphyp;niomanoineter  has  been  devLsed  by  Riva-Rocci.i  A 
rubber  pouch  iiioasuriuj;  5  cm.  in  width  and  possessing  a  lonRth  sufficient  to 
encircle  the  arm,  is  coniiectcd  with  a  mercury  reservoir  and  a  pressure  bulb.  This 
rubber  hug  Ls  protected  upon  its  outside  by  a  leather  or  canvas  cuff  which  is 
tightened  until  it  fits  the  arm  snugly.  The  arm  is  j)laced  in  an  easy  position  at 
the  level  of  the  heart,  and  consequently,  no  corrections  need  be  made  for  the 
hydrostatic  effects.  If  the  pouch  is  now  inflated,  the  pressure  in  this  system 
rises  until  the  tissues  around  the  brachial  artery  are  compressed  in  such  a  degree 
that  the  lumen  of  this  blood-vessel  is  obliterated.  This  moment  is  clearly  marked 
by  the  disappearance  of  the  pulsations  in  the  radial  artery,  while  the  pressure 
necessary  to  accomplish  this  end  is  registered  by  the  manometer  of  the  mercury 
reservoir.  The  l)est  procedure  to  be  followed  is  this:  The  cuff  having  been 
properly  adjusted,  the  fingers  of  the  left  hand  are  placed  upon  the  radial  artery  at 


Fig.    191. — RrvA-Rocci's    Sphygmomanometer.     (From    Janeway's    "Clinical  Study  of 
Blood-proisure,"   D.   Appleton  and  Co.,  Publishers.) 


the  wrist,  while  the  right  hand  is  employed  to  inflate  the  rubber  pouch.  The 
pressure  is  read  at  the  very  moment  when  the  radial  pulse  disappears.  In  quite 
the  same  way,  the  pressure  is  again  noted  when  the  pulse  reappears  during  the 
gradual  deflation  of  the  pouch.  The  principal  involved  in  this  procedure  is 
obvious.  When  the  outside  pressure  just  barely  overcomes  the  intravascular 
pressure,  as  is  indicated  by  the  loss  of  the  radial  pulse,  the  former  may  correctly 
be  taken  as  a  measure  of  the  latter.  Naturally,  this  procedure  does  not  permit 
of  definite  conclusions  being  drawn  regarding  the  mean  blood  pressure,  but  indi- 
cates solely  the  maximum  or  systolic  blood  pressure,  i.e.,  the  moment  when  the 
peaks  of  the  individual  pulse  waves  are  just  capable  of  overcoming  the  outside 
pressure. 

1  Gaz.  med.  di.  Torino,  1896. 


368     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

The  Method  of  Auscultation. — The  moment  of  the  disappearance 
and  reappearance  of  the  pulse  may  also  be  determined  by  means  of 
auscultation,  because,  as  !Marey  has  noted,  the  constriction  of  an  artery 
gives  rise  to  noises  (bruit  de  souffle)  which  are  heard  best  distally  to 
and  in  the  immediate  vicinity  of  the  constriction.  Thus,  if  a  stetho- 
scope is  applied  over  the  brachial  artery  below  the  border  of  the  arm- 
piece,^  the  gradual  deflation  finally  gives  rise  to  a  sharp  blowing  sound 
which  presently  becomes  fuller  and  then  disappears  altogether.  The 
first  occurrence  of  this  sound  indicates  the  systolic  height  of  the  blood 
pressure,  while  the  moment  at  which  the  sound  becomes  muffled  shortly 
before  its  complete  disappearance,  corresponds  to  its  diastolic  value. 
The  mean  pressure  can  only  be  obtained  in  an  approximate  way  with 
the  help  of  these  two  extremes. 

The  Graphic  Method. — The  determination  of  the  blood  pressure 
may  also  be  attempted  iti  accordance  with  the  principle  that  the 
arterial  wall  executes  its  greatest  movements  at  a  time  when  the 
intravascular  pressure  is  accurately  balanced  by  the  outside  pressure. 
This  fact  to  which  attention  was  first  called  by  IMarey,  has  been  proven 
experimentally  by  Mosso  upon  excised  segments  of  arteries.  The 
idea  is  to  oppose  the  intravascular  pressure  by  an  outside  pressure 
which,  being  equal  to  that  within,  permits  the  most  perfect  elastic 
play  of  the  arterial  walls.  Thus,  if  the  hand  is  placed  in  a  receptacle 
filled  with  mercur}',  the  pulse  is  felt  either  at  the  base  of  the  thumb 
or  along  the  fingers.  In  accordance  with  von  Frey,^  the  pressure 
prevailing  in  the  blood-vessels  of  the  hand  may  be  obtained  by  deter- 
mining in  millimeters  the  depth  to  which  it  must  be  pushed  into  the 
mercury  in  order  to  produce  this  subjective  phenomenon.  In  a  simi- 
lar way,  it  is  possible  to  register  the  arterial  pressure  upon  the  paper 
of  a  kymograph  by  simply  connecting  a  recording  tambour  with  the 
cuff  of  a  sphygmomanometer  or  with  the  free  end  of  its  mercurial  in- 
dicator. During  the  complete  compression  of  the  brachial  artery,  the 
pulsations  so  registered  retain  a  small  amphtude,  because  they  are 
simply  transmitted  from  the  central  end  of  this  blood-vessel.  WTien 
however,  the  outside  pressure  is  lowered  step  by  step,  their  size  is 
gradually  increased  up  to  the  time  when  the  diastohc  mean  value  of  the 
blood  pressure  has  been  reached.  Subsequent  to  this  point  the  con- 
spicuousness  of  these  oscillations  is  again  diminished.  In  this  way, 
the  moment  may  be  accurately  determined  at  which  the  outside  or 
extravascular  pressure  precisely  equals  the  intravascular  pressure. 
Quite  similarly,  if  the  pressure  is  gradually  increased,  the  beginning 
of  the  large  oscillations  indicates  the  diastolic  minimum. 

This  procedure  must  be  followed  if  measurements  are  undertaken 

'  In  accordance  with  Janowski,  Mlinchener  med.  Wochenschr,  1907,  the  aus- 
cultation method  was  first  employed  by  Karotkovv  in  1895.  Also  see:  Strass- 
burger,  D.  Archiv  fiir  kUn.  Med.,  1907,  459,  and  Fellner,  Verhandl.,  Kongr.  fiir 
inn.  Med.,  1907. 

2  Festschrift  fiir  B.  Schmidt,  Leipzig,  1896,  79. 


BLOOD    PRESSURE 


369 


with  the  sphyp;momanomcters  devised  by  Erlanger'  and  Miinzer^  or 
with  the  sphy{j;ni()S('opc  of  Binp;,^  or  the  oscilloinctor  of  Withner/  It 
is  true,  however,  that  the  greatest  numl)er  of  instruments  of  this  kind 
are  modifications  of  the  Riva-Rocci  apparatus^  described  previously. 
The  fundamental  principle  has  remained  the  same  in  all  cases  and  only 
insignificant  changes  have  been  made.  Thus,  it  has  been  shown  by 
direct  measurements,  that  a  narrow  arm-piece  gives  somewhat  lower 
values,  and  hence,  a  much  broader  one,  measuring  12  cm.  in  width,  is 
now  most  commonly  employed.     In  addition,  the  original  mercury- 


FiG.  192. — Janeway's  Sphygmomanometer. 
A,  folding  U  tube;  B,  arm  cuff;  C,  pressure  bulb;  D  and  E,  needle-valve  for  release 
of  pressure;  F,  cork  for  closing  end  of  mercury  tube. 


reservoir  has  been  displaced  in  several  of  them  by  a  modern  mercury 
manometer  to  which  a  more  convenient  and  patent  form  has  been  given 
so  that  it  can  be  carried  from  place  to  place  without  spilUng  the  mer- 
cury. An  ordinary  valved  rubber  bulb  may  be  used  for  the  inflation 
and  deflation  of  the  cuff.  By  using  the  metal  tonometer  devised  by 
V.  Basch,  as  a  sample,  certain  instruments  have  recently  been  con- 

1  Am.  Jour,  of  Phjsiol.,  Proc.  xxii,  1902,  also  ibid.,  x,  1904. 

*  Miinchener  med.  Wochenschr.,  1907,  1357. 
3  Berliner  klin.    Wochenschr.,    1907,   690. 

^  Vaquez,  Cgmpt.  rend.,  Ixvi,  and  Paris  medicale,  1911. 

*  Gartner,  Wiener  med.  Wochenschr.,  xxxi,  1899,  and  Martin,  Miinchener  med. 
Wochenschr.,  xxiv,  1903. 

24 


370     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

structed  in  which  a  metal  spring^  is  employed  instead  of  the  mercury 
manometer.  These  so-called  sphygmotonometers  possess  the  advan- 
tage of  being  convenient  to  handle,  although  they  must  be  calibrated  re- 
peatedly to  make  sure  that  the  tension  of  the  spring  has  not  changed. 
The  Factors  Influencing  the  Arterial  Pressure. — As  far  as  the 
influence  of  age  is  concerned,  it  has  been  well  substantiated  that  the 
arterial  blood  pressure  increases  constantly  until  the  normal  mean  is 
reached  in  adult  life.  In  later  years  and  old  age,  it  again  increases 
owing  to  the  fact  that  the  elasticity  of  the  vascular  tissue  diminishes 
steadily  at  this  time  in  consequence  of  retrogressive  changes.  These 
facts  are  fully  illustrated  by  the  succeeding  table  in  which  values  fur- 
nished by  Cook  and  Briggs,^  Shaw,^  McCurdy  and  Thayer^  have 
been  included: 

First  few  months 70-75  mm.  Hg 

1-2  years 80-90  mm.  Hg 

2-3  years 90-100  mm.  Hg 

3-10  years 95-1 15  mm.  Hg 

10-15  years.  ..;<', 100-115  mm.  Hg 

15-20  years.  .'.'^ 105-128  mm.  Hg 

20-30  years <^ 135  mm.  Hg 

30-40  years 140  mm.  Hg 

40-50  years 142  mm.  Hg 

50—60  years 154  mm.  Hg 

60-70  years 180  mm.  Hg 

Janeway^  considers  150  mm.  Hg  as  the  upper  limit  in  normal  adults, 
while  a  systolic  pressure  of  60-75  mm.  Hg  is  generally  regarded  as 
dangerously  low,  although  a  pressure  of  30-40  mm.  Hg  is  sometimes 
observed  during  operations.  The  average  normal  systolic  pressure 
amounts  to  135-145  mm.  Hg;  women  generally  showing  a  somewhat 
lower  pressure  than  men.  Persons  with  sedentary  habits  usually 
exhibit  a  pressure  between  120  and  125  mm.  Hg.  The  diastolic  pres- 
sure most  frequently  retains  a  value  about  35-40  mm.  Hg  below  that 
of  the  systolic.^  If  the  pressure  persists  for  longer  periods  of  time 
at  180-200  mm.  Hg,  and  over,  a  condition  of  hypertension  is  said  to 
exist.  Quite  similarly,  persistent  low  pressures  indicate  a  state  of 
hypotension.  Both  conditions  generally  possess  pathological  causes. 
The  pressure  is  lowest  during  the  first  hours  of  sleep,  and  rises 
gradually  until  the  time  of  awakening,  when  it  increases  rather  sud- 
denly to  a  level  somewhat  higher  than  that  retained  before  retiring.'^ 
During  the  day  the  blood  pressure  shows  considerable  variations  which 

1  von  Recklinghausen,  Archiv  fiir  exp.  Pathol.,  Iv,  1906,  375. 

2  Johns  Hopkins  Univ.  Report,  xi,  1903,  451. 

3  Albany  Med.  Jour.,  xxi,  1900,  88. 

^  Am.  Jour.  Med.  Sciences,  cxxvii,  1904,  391. 
°  Clin.  Study  of  Blood  Pressure,  New  York,  1904. 

^  Hirschf elder.  Diseases  of  the  Heart  and  Aorta,  Lippincott,  Philadelphia,  1913, 
and  Faught,  Blood  Pressure,  Saunders  Co.,  1916. 

^  Brush  and  Fayerweather,  Am.  Jour,  of  Physiol.,  v,  1901,  199. 


BLOOD    PRESSURE  371 

must  bo  attributed  to  divorso  external  and  internal  influences.  Fluc- 
tuations of  50  to  00  mm.  Hg  are  not  uncommon.  Meals  possess  an  aug- 
mentor  effect,  in  spite  of  the  fact  that  the  portal  blood-vessels  receive 
large  quantities  of  blood  during  the  periods  of  digestion.^  Janeway's 
charts  show  a  rise  of  5  mm.  Hg  in  the  systolic  and  a  fall  of  5  mm.  Hg 
in  the  diastolic  pressure  after  the  midday  and  evening  meals.  To 
this  augmentor  effect,  as  well  as  to  the  sudden  reflex  vasoconstrictor 
reaction,  must  be  attributed  the  peculiar  cerebral  symptoms  which 
are  frequently  experienced  after  too  hearty  a  meal.  Apoplectic  seiz- 
ures are  prone  to  occur  under  these  circumstances,  provided,  of  course, 
that  the  arteries  have  been  rendered  brittle  by  calcareous  infiltration. 
Deep  and  forced  breathing  increases  the  pressure.  It  is  decreased 
during  menstruation,^  but  rises  during  pregnancy,^  especially  during 
its  later  stages,  and  shows  a  most  decided  increase  during  labor  in 
consequence  of  the  pronounced  sensory  stimulations  and  musculo- 
motor  efforts.  Baths  at  the  temperature  of  the  body  have  no  marked 
effect,  but  cold  baths  (30-35°  C.)  produce  a  rise  in  the  systolic  pressure. 
Hot  baths  (40°  C.  and  over)  generally  possess  a  similar  effect  on  account 
of  the  resulting  increase  in  the  frequency  of  the  heart.*  Water  con- 
taining carbon  dioxid,  acts  augmentatively,  but  only  if  the  cardiac 
energy  has  not  been  diminished. 

As  far  as  the  influence  of  muscular  exercise  is  concerned,  the  more 
recent  determinations  which  have  been  made  with  the  help  of  the  in- 
direct method,  seem  to  fully  bear  out  the  results  obtained  in  horses 
and  dogs  at  an  earlier  date  by  means  of  the  direct  method.^  Thus, 
Hill^  has  shown  that  on  moving  about,  the  pressure  rises  from  10  to 
20  mm.  above  that  shown  when  at  rest  or  asleep.  Furthermore,  the 
experiments  of  Edgecomb  and  Bain,^  Masing,^  Karrenstein,^Lowsley,^" 
and  others  have  demonstrated  that  the  effect  of  muscular  work  depends 
entirely  upon  its  severity.  In  all  forms  of  it,  an  initial  rise  results, 
which  is  retained  for  a  time  if  the  muscular  efforts  have  been  slight, 
or  is  displaced  by  a  fall,  if  the  exercise  has  been  severe  or  of  long 
duration.  A  moderate  fall  in  arterial  pressure,  however,  is  not  an 
uncommon  symptom  of  moderate  muscular  work. 

1  Gumprecht,  Zeitschr.  flirklin.  Med.,  xxxix,  1900;  Jellinek,  ibid.,  xxxix,  1900; 
Somerfeld,  Dissertation,  Erlangen,  1901,  and  Janeway,  Clin.  Study  of  Blood 
Pressure,  New  York,  1904. 

^  Federn,  Wien.  klin.  Wochenschr.,  xv,  1912. 

'  Wiessner,  Deutsch.  Arch,  fiir  klin.  Med.,  1907,  and  O.  Miiller,  Kongr.  fiir 
Inn.  Med.,  1902. 

*  Strasburger,  Zeitschrift  fiir  klin.  Med.,  liv,  1904,  373. 

^  Zuntz  and  Hagemann,  Deutsch.  med.  Wochenschr.,  1892,  and  Kaufmann, 
Archiv  de  phvsiol.,  ser.  51t.  4. 

6  Jour,  of  Physiol.,  xxii,  1898,  Proc.  26. 

'  Ibid.,  xxiv,  1899,  48. 

«  Deutsch.  Arch,  fiir  klin.  Med.,  Ixxiv,  1902. 

9  Zeitschr.  fiir  klin.  Med.,  i,  1903. 

1"  Am.  Jour,  of  Physiol,  xxvii,  1911,  446. 


372      THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

While  ordinary  changes  in  position^  do  not  affect  the  blood  pres- 
sure very  materially,  extreme  changes  always  induce  static  effects 
which  the  vascular  system  is  at  times  unable  to  counteract.  Thus,  a 
change  from  the  recumbent  to  the  standing  position  always  leads  to  a 
fall  in  blood  pressure,  if  the  tonus  of  the  blood-vessels  has  been  lessened 
in  any  way.  This  condition  may  be  general  or  local,  and  is  especially 
prone  to  involve  the  blood-vessels  of  the  portal  system.  As  these 
channels  are  concerned  with  the  digestion  and  absorption  of  foods, 
they  must  absorb  a  large  mass  of  blood,  and  hence,  their  static  in- 
fluence must  be  particularly  potent  at  this  time.  The  effects  of  vascu- 
lar relaxation  are  counteracted  in  a  large  measure  by  a  greater  ven- 
tricular discharge,  because  if  a  person  assumes  the  erect  position,  the 
heart  beats  more  quickly,  this  increase  being  proportional  to  the  fall 
in  pressure.  If,  however,  the  relaxation  is  pronounced,  the  heart  is 
quite  unable  to  effect  an  adequate  coiyipensation  and  a  fall  in  blood 
pressure  results.  Concurrently,  it  may  be  concluded  that  a  proper 
tonicity  of  the  blood-vessels  suffices  to  retain  the  pressure  at  its  normal 
level  without  that  the  heart  need  increase  its  energy.  In  fact,  a  person 
whose  vascular  system  is  tonically  set,  most  frequently  shows  a  slight 
rise  on  assuming  the  erect  position,  because  the  heart  nevertheless 
tends  to  increase  its  frequency  by  at  least  a  few  beats. 

These  facts  have  been  employed  by  Crampton^  in  obtaining  an  index  of  con- 
dition. A  large  number  of  determinations  of  the  blood  pressure  in  normal  indi- 
viduals have  been  compiled  in  such  a  way  that  their  state  of  phj^sical  fitness  may 
be  deduced  directly  from  these  figures.  This  is  made  possible  bj'  arranging  these 
values  in  series  in  accordance  with  the  alterations  in  the  height  of  the  blood  pres- 
sure and  the  frequency  of  the  heart  which  resulted  when  these  persons  changed 
their  position  from  the  recumbent  to  the  upright.  In  accordance  with  these  deter- 
minations, a  person  is  said  to  be  in  a  good  physical  condition  if,  on  assuming  the 
erect  position,  his  systolic  pressure  diminishes  by  no  more  than  12  nor  increases  by 
more  than  18  mm.  Hg.  Besides,  this  change  must  leave  the  diastolic  pressure  un- 
changed, or  must  not  increase  it  by  more  than  18  mm.  Hg.  Quite  similarly,  the 
heart  must  at  this  time  either  retain  its  previous  rate  or  increase  its  frequency  by 
no  more  than  40  beats.  Greater  variations  than  these  are  regarded  as  proving 
that  the  vascular  system  is  relaxed  and  that,  therefore,  the  person  is  in  a  poor  phys- 
ical condition.  While  this  test  possesses  a  sound  dynamical  basis,  the  results  ob- 
tained should  be  accepted  with  great  reserve  and  should  not  he  applied  with  undue 
strictness  to  all  persons. 

It  should  be  mentioned  that  tests  of  physical  fitness  have  also  been  devised 
by  Graupner,'  and  Katzenstein.''  The  former  endeavored  to  test  the  functional 
capacity  of  the  heart  by  noting  the  influence  of  a  measured  amount  of  muscular 
work  upon  the  blood  pressure  and  pulse  rate,  and  the  latter,  by  determining  the 
response  of  the  heart  to  compression  of  both  iliac  arteries.  Barach*  has  sought  to 
determine  the  tonic  condition  of  the  circulatory  system  by  multiplying  the  systolic 

1  Shapiro,  Med.  Jahrb.  der  K.  K.  Gesellsch.  d.  Arzte,  1882;  Erlanger  and 
Hooker,  Johns  Hopkins  Hosp.  Rep.,  xii,  1904,  and  Brocking,  Zeitschr.  fiir  Exp. 
Path.,  ix,  1907. 

-  Med.  News,  1905. 

^  Berliner  klin.  Wochenschr.,  1902. 

*  Ibid.,  1907. 

'  Jour.  Am.  Med.  Assoc,  1914. 


BLOOD    PRESSURE  373 

and  diastAlic  prossures  by  tho  piilso  rate.  When  added  to  one  another,  the  values 
so  obtained  f^ive  the  so-called  S.  D.  R.  index,  for  example: 

Systolic  pressure  120  mm.  IIk  X  72  =    8,640  mm.  Hr 
Diastolic  pressure  70  mm.  lip;  X  72  =    5,040  mm.  Hr 

190  mm.  Hr  X  72  =  13,680  mm.  Hg 

By  combining  in  this  way  the  pressure  with  the  cardiac  frequency,  it  is  possible 
to  obtain  an  estimate  of  the  vascular  energy  for  longer  periods  of  time.  The  high- 
est S.  D.  R.  index  which  has  been  observed  in  normal  persons  is  close  to  20,000. 
Thus,  a  person  with  a  total  energy  index  of  30,000  may  be  said  to  show  a  50  per 
cent,  increase,  and  so  on.  The  lower  limit  .seems  to  lie  at  about  the  figure  12,000. 
The  efficiency  test  descril)ed  by  Barringer^  consists  in  determining  the  cardiac 
rate  and  blood-pressure  before  and  after  a  graded  exercise  which  may  be  determined 
in  foot-pounds. 

The  Venous  Blood  Pressure. — It  has  been  stated  aoove  that  the 
venous  pre.^^.sure  may  be  determined  in  any  vein  of  convenient  size 
and  location  by  connecting  it  by  means  of  a  T-tube  with  a  U-shaped 
manometer  containing  normal  saline  solution.  In  this  way,  the  lateral 
pressure  is  obtained  which  prevails  in  this  vein  at  the  point  of  insertion 
of  the  tube.  By  simultaneously  registering  the  pressure  in  different 
veins  of  the  dog,  Burton-Opitz-  has  obtained  the  following  average 
values: 

Saphenous  vein  (left) 7 .  42  mm.  Hg 

Femoral  vein  (left) 5. 39  mm.  Hg 

Femoral  vein  (right) 5 .  42  mm.  Hg 

Facial  vein  (left) 5 .  12  mm.  Hg 

Brachial  vein  (right) 3 .  90  mm.  Hg 

Renal  vein 10.9    mm.  Hg 

Mesenteric  vein 14.7    mm.  Hg 

Splenic  vein 10.1    mm.  Hg 

Portal  vein 8.9    mm.  Hg 

External  jugular  vein  (left) 0. 52  mm.  Hg 

External  jugular  vein  (right) — 0 .  08  mm.  Hg 

Superior  cava  (per.    portion) —  1 .  38  mm.  Hg 

Superior  cava  (centr.  portion) —2.  96  mm.  Hg 

Inferior  cava  at  hep.  vein 0 .  00  mm.  Hg 

This  compilation  shows  that  the  pressure  decreases  gradually 
from  the  periphery  to  the  center  at  the  rate  of  about  1  mm.  Hg  for 
every  35  mm.  of  distance.  The  zero-line  is  reached  in  close  proximity 
to  the  chest.  Centrally  to  this  point,  the  pressure  becomes  negative 
and  eventually  attains  its  lowest  value  in  the  auricular  portion  of  the 
heart,  namely  — 10  to  — 15  mm.  Hg.  As  the  pressure  in  the  peripheral 
veins  is  only  10  to  15  mm.  Hg,  the  total  fall  in  the  venous  system 
amounts  to  no  more  than  30  mm.  Hg.  It  should  also  be  remembered 
that  this  fall  is  had  only  because  the  soft  walls  of  the  venous  channels 
are  constantly  exposed  to  the  elastic  pull  of  the  lungs  which  becomes 
greatest   during  inspiration.     This  can  readily  be  proved,   because 

1  Arch,  of  Int.  Med.,  March,  1916. 

*Am.  Jour,  of  Physiol.,  ix,  1903;  also  Pfliiger's  Archiv,  cxxix,  1908. 


374     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

if  the  chest  is  opened,  the  pressure  in  the  central  veins  rises  immediately 
to  above  zero  with  a  corresponding  elevation  of  the  pressure  from  here 
outward.  Hence,  it  may  be  concluded  that  this  negative  venous  pres- 
sure is  dependent  upon  the  elastic  recoil  of  the  lungs. 

nder  normal  conditions,  the  area  of  negative  venous  pressure 
begins  at  about  the  junction  of  the  hepatic  vein  with  the  inferior 
cava,  and  at  the  point  where  the  external  jugular  vein  passes  deep 
into  the  supraclavicular  fossa.     The  so-called  "danger  line"  of  the 


Fig.   193. — Diagr.\:m  to  Pressure  Throughout  the  Vascular  System. 
Z,  abscissa  or  zero-line;  P,  cur^^e  of  pressure  (A)  in  arteries  (C)  in  capillaries  and  (F) 
in  veins.     The  greatest  fall  in  pressure  occurs  in  the  capillaries  in  which  the  resistance  is 
greatest. 

surgeon  corresponds  to  this  line  of  zero  pressure,  because  it  has  always 
been  thought  that  an  injury  to  a  vein  centrally  to  this  point,  must 
inevitably  lead  to  an  entrance  of  air  into  the  vascular  system  and  a 
frothing  of  the  blood  by  the  cardiac  valves.  This  danger,  however, 
is  not  so  imminent  as  might  be  supposed,  because  the  walls  of  the  veins 
yield  easily  and,  as  they  are  not  firmly  attached  to  the  surrounding 
tissues,  collapse  very  readily,  thereby  preventing  the  ingress  of  air. 
Moreover,  while   dangerous   on  account  of  the  possible  occurrence 

of  emboli,  small  quantities  of  air  are  fre- 

^^^^^^^  quently  gotten  rid  of  by  absorption. 

^^HPNHj^  The  principle  of  the  indirect  method 

^      Y^M^  of   measuring   venous    blood    pressure   is 

^^^^^^^W^"^"^^^    precisely  the  same  as  that  made  use  of  in 

^^K^^^^^w  determining   the    arterial    pressure.     An 

^^^B^^  outside  pressure  which  can  be  accurately 

Fig.  194.— Small  Rubber  measured,    is    brought   to   bear   upon   a 

Capsule  Used  for  Obliteration  r-    •    i  •  j.-i     v  a      i      j.        _ 

OF  Vein  Superficial    vein    until    its   central   stump 

becomes  empty.  As  the  venous  pressure 
is  low,  a  water  manometer  is  employed  as  the  indicator  in  conjunc- 
tion with  an  ordinary  pressure  bulb.  In  accordance  with  v.  Reckling- 
hausen,^ the  obliteration  of  the  vein  is  accomplished  by  means  of  a 
small  capsule  of  thin  rubber  (Fig.  194)  which  communicates  with  a 
manometer  and  is  held  in  place  upon  the  skin  by  a  flat  box  made  of 
glass  or  wood.  Hooker^  employs  a  small  glass  chamber  which  is 
fastened  to  the  skin  in  the  region  of  the  vein  by  a  film  of  collodion 
solution. 

1  Archiv  fiir  Exp.  Path,  und  Pharm.,  Iv,  1906. 

2  Am.  Jour,  of  Physiol.,  Ixxiii,  1914,  Proc.  27. 


BLOOD    PRESSURE 


375 


The  compression  of  th(^  vein  can  also  be  a(!complishod  \)y  moans 
of  a  sprinji;  manometer  such  as  was  first  employed  by  von  Frey,'  or 
by  means  of  a  cuff  connected  with  a  water  manometer.  Frank  and 
Reh,2  for  example,  use  two  cuffs,  one  of  which  is  applied  to  the  fore- 
arm and  the  other  to  the  arm.  The  former  is  inflated  so  as  to  fit 
snugly,  but  without  exerting  a  pressure  of  more  than  1  cm.  H2O. 
The  arm-cuff  is  then  inflated  slowly  until  the  pressure  in  the  manometer 
connected  with  the  lower  cuff,  is  suddenly  seen  to  rise.  This  change 
is  taken  to  indicate  an  increase  in  the  volume  of  the  arm  caused  by  the 
obstruction  to  the  venous  return  distally  to  the  arm  cuff.  When  this 
obstruction  first  becomes  evident,  the  pressure  in  the  distal  cuff  must 
equal  the  venous  pressure.  Obviously,  these  determinations  must 
either  be  made  at  the  level  of  the  heart  or  must  be  corrected  for  this 
level,  because  the  pressure  in  any  vein  varies  with  its  position.  Thus, 
if  the  arm  is  allowed  to  hang  pendant  at  the  side,  the  pressure  in  the 


Fig.   195. — Method  of  Measuring  Venous  Blood-pressure. 
The  rubber  capsule  is  adjusted  upon  the  vein  and  is  covered  with  a  glass  plate  or 
small  box  glued  to   the  surface  with  collodion.     The  capsule  is  connected  with  a  ma- 
nometer and  pressure-bulb.     (v.    Recklinghausen.) 


veins  of  the  hand  is  much  greater  than  when  it  is  elevated  to  a  point 
above  the  heart. 

Gartner^  has  advised  the  following  procedure.  If  the  arm  is 
slowly  raised,  the  veins  of  the  hand  collapse  as  soon  as  a  certain  level 
has  been  reached.  If  the  distance  between  this  level  and  that  of  the 
heart  at  the  junction  of  the  fifth  costal  cartilage  with  the  sternum  is 
now  measured,  we  obtain  the  pressure  supporting  the  blood  at  the 
right  auricle  in  centimeters  of  blood,  or  water,  because  10  cm.  of  blood 
equal  10.6  cm.  of  water.  Moritz  and  Tabora^  have  called  attention 
to  the  fact  that  the  venous  pressure  corresponds  to  the  pressure  neces- 
sary to  cause  normal  saline  solution  to  enter  the  body.  If  the  infusion 
is  made  through  the  median  vein  of  the  arm  when  placed  at  the  level 
of  the  heart,  the  pressure  in  this  vein  must  correspond  to  the  height 
of  the  column  of  saline  solution  still  left  in  the  buret  at  the  end  of  the 
injection.     It  is  of  interest  to  note  that  the  values  obtained  with  the 

^  Deutsch.  Archiv  fiir  klin.  Med.,  Ixxiii,  1902. 

2  Zeitschr.  fiir  Exp.  Path,  und  Therap.,  1912;  also  see:  A.  A.  Howell  in  Arch, 
fur  int.  med.,  ix,  1912. 

^  Mtinchener  med.  Wochenschr.,  Ixxlv,  1904. 
*  Deutsch.  Archiv  fiir  klin.  Med.,  xcviii,  1910. 


376     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

aid  of  these  indirect  methods  closely  agree  with  those  given  previously. 
Thus,  it  has  been  found  that  the  pressure  in  the  small  veins  of  the  arm 
and  hand  amounts  to  100-200  cm.  H2O. 

The  Capillary  Blood  Pressure. — Obviously,  the  pressure  prevailing 
in  the  capillaries  cannot  be  measured  by  the  direct  method;  in  fact, 
even  the  indirect  procedures  so  far  devised  have  given  only  approxi- 
mate values.  Thus,  v.  Kries^  has  made  use  of  a  thin  plate  of  glass 
which  he  placed  upon  the  skin  and  gradually  weighted  until  the  skin 
underneath  it  became  pale.  This  method  is  based  upon  the  proba- 
bility that  the  first  indication  of  the  paling  of  the  surface  corresponds 
to  the  moment  when  the  pressure  in  the  capillaries  is  balanced  by  the 
pressure  without.  The  latter  may  be  expressed  in  centimeters  of 
water  by  dividing  the  weight  which  has  been  placed  upon  the  glass 
slide  by  the  size  of  the  area  under  compression.  Roy 
and  Graham-Brown^  have  attempted  to  determine  the 
moment  of  compression  of  the  capillaries  by  exposing 
them,  while  under  microscopic  observation,  to  a  pres- 
sure brought  to  bear  upon  them  by  means  of  elastic 
capsules  connected  with  a  manometer. 

When  the  arm  was  held  at  the  level  of  the  heart, 
the  pressure  in  the  capillaries  of  the  fingers  amounted 
to  24  mm.  Hg.  With  the  hand  pendant  at  the  side 
of  the  body,  the  pressure  rose  to  62  mm.  Hg.  In  the 
capillaries  of  the  ear,  the  pressure  amounted  to  20  mm. 
Hg  and  in  those  of  the  gums  of  a  rabbit,  to  33  mm. 
Apparatus  OF  Hg.  The  determinations  of  von  Recklinghausen^  have 
VON  Kries  for  given  a  value  of  55  mm.  Hg  for  the  small  arterioles 
i^^RrB  Lo^oT-  supplying  the  capillaries  of  the  tips  of  the  fingers. 
PRESSURE.  While  the  capillary  pressure  must  vary  in  different 

organs  and  tissues,  it  seems  that  its  average  value 
must  lie  somewhere  between  40  and  50  mm.  Hg.  To  illustrate :  If  the 
intraventricular  pressure  is  125  mm.  Hg,  it  will  be  found  that  the 
peripheral  arterial  pressure  amounts  to  about  105  mm.  Hg.  About 
3  or  4  mm.  Hg  of  the  initial  driving  force  are  lost  between  the  heart 
and  the  aorta  and  the  remainder  between  this  blood-vessel  and  the 
arterioles.  Distally  to  these,  the  original  driving  force  is  used  up  very 
rapidly,  the  greatest  reduction  occurring  in  the  capillaries  proper. 
This  cannot  cause  surprise,  because  the  resistance  in  these  channels 
is  very  great.  As  we  have  seen,  the  blood  arrives  in  the  distal  veins 
under  a  pressure  of  only  about  10  to  15  mm.  Hg  and  hence,  almost 
100  mm.  Hg  of  the  original  pressure  have  been  used  up  in  forcing  the 
capillary  passage.  As  the  blood  approaches  the  heart,  the  pressure 
becomes  less  and  less,  amounting  at  the  cardiac  vestibule  to  only  —5 
to   —10  mm.  Hg.     Naturally,  these   negative  values  which  are  de- 

1  Verh.  siichs.  Gesellsch.  der  Wissensch.,  1S75. 

2  Jour,  of  Physiol.,  ii,  1879,  323. 

^  Archiv  fiir  Exp.  Path,  und  Pharmak.,  Iv,  1907. 


THE  PULSATORY  VARIATIONS  IN  BLOOD  PRESSURE     377 

pcndont  upon  the  elastic  pull  of  the  lungs  upon  the  soft  walls  of  the 
central  veins,  serve  as  accessory  means  to  augment  and  to  conserve 
the  initial  driving  force  of  the  heart. 


CHAPTER  XXXII 

THE  PULSATORY  VARIATIONS  IN  BLOOD  PRESSURE 

A.  THE  CARDIAC  VARIATIONS  IN  ARTERIAL  PRESSURE 

The  Cause  of  the  Arterial  Pulse. — Fluctuations  in  pressure  are 
encountered  in  the  arteries  as  well  as  in  the  veins;  in  fact,  they  are 
also  perceptible  at  times  in  the  capillaries.  They  possess  a  twofold 
origin,  being  caused  either  by  the  contractions  of  the  heart,  or  by  the 
movements  of  respiration.  If  the  former,  they  are  designated  as  the 
cardiac,  and  if  the  latter,  as  the  respiratory  variations  in  blood  pressure. 
Moreover,  as  each  group  of  changes  makes  itself  felt  in  the  arteries 
as  well  as  in  the  veins,  they  are  again  subdivided  into  the  cardiac  varia- 
tions in  arterial  and  venous  blood  pressure,  and  into  the  respiratory 
variations  in  arterial  and  venous  pressure.  The  principal  changes 
due  to  the  activity  of  the  heart,  are  the  so-called  arterial  pulse  and  the 
physiological  venous  pulse. 

Each  ventricular  systole  adds  a  certain  quantity  of  blood  to  that 
already  transferred  into  the  arterial  system  by  the  preceding  systoles. 
The  arterial  pressure  increases  with  each  ventricular  discharge  above 
that  prevailing  during  the  previous  diastolic  period.  Furthermore, 
owing  to  the  elasticity  of  the  arterial  channels,  each  inrush  of  blood 
causes  a  distention  of  their  walls  which  is  followed  by  a  recoil  as  soon 
as  the  influx  has  ceased.  Obviously,  this  elastic  play  serves  the  pur- 
pose of  lessening  the  systolic  strain  upon  the  cardiac  muscle  as  well  as 
that  upon  the  walls  of  the  blood-vessels,  because  if  the  heart  were 
forced  to  pump  into  a  system  of  rigid  tubes,  its  contractions  would 
necessarily  become  labored,  owing  to  the  fact  that  a  certain  amount  of 
blood  would  first  have  to  be  dislodged  from  the  tubes  before  a  new 
amount  could  be  accommodated  therein.  A  condition  of  this  kind 
would  occasion  a  periodic  escape  of  venous  blood  to  counterbalance 
the  quantitj^  of  arterial  blood  forced  in,  and  this  intermittent  or  re- 
mittent flow  would  be  characterized  by  very  liigh  systoHc  and  very  low 
diastolic  pressures. 

Contrary  to  this  result,  the  distensibihty  of  the  arterial  walls 
enables  this  system  to  accommodate  the  successive  outputs  of  the  heart 
by  simply  enlarging  its  caliber.  Moreover,  this  process  insures  the 
least  possible  expenditure  of  energy  and  does  not  permit  of  the  develop- 
ment of  disturbing  fluctuations  in  pressure  and  flow.  In  addition, 
the  subsequent  recoil  of  the  arterial  walls  serves  the  purpose  of  con- 


378     THE    MECHANICS    OF    THE    CIBCULATION,    HEMODYNAMICS 

tinuing  the  initial  driving  force  of  the  heart  even  during  the  diastolic 
period,  so  that  the  blood  is  forced  to  escape  into  the  capillaries  in  a 
perfectly  steady  stream  and  not  remittently.  Obviously,  therefore, 
the  pressure  in  the  arteries  is  increased  during  each  systole  of  the  heart, 
and,  as  the  ventricles  are  emptied  rather  quickly  (0.3  sec),  this  rise 
must  develop  with  a  certain  abruptness.  The  diastolic  decline,  on  the 
other  hand,  is  gradual,  because  the  peripheral  resistance  is  adjusted 
in  such  a  way  that  a  very  copious  escape  of  arterial  blood  during 
this  period  cannot  result.  By  means  of  a  proper  adjustment  of  this 
resistance,  the  arterial  system  is  constantly  kept  in  a  condition  of 
overfilling. 

The  aforesaid  systolic-diastolic  variation  in  the  arterial  pressure 
forms  the  basis  of  the  arterial  pulse.  Although  primarily  dependent 
upon  the  activity  of  the  heart,  its  place  of  origin  is  really  in  the  root  of 
the  aorta,  whence  the  individual  fluctuations  in  pressure  are  trans- 

O  liOmm- 


Fia.   197. — The  Cardiac  Variations  in  the  Arterial  Blood-pressure. 
S,   systolic  pressure;    D,    diastolic  pressure;   M,   average  pressure.     The   systolic- 
diastolic  difference  constitutes  the  pulse-pressure.     A,  abscissa. 

mitted  throughout  the  arterial  system  in  the  form  of  successive  waves. 
Thus,  it  happens  constantly  that  the  central  portion  of  this  system  is  in 
a  state  of  maximum  distention,  while  its  more  distal  segments  still 
retain  their  diastolic  caliber.  A  moment  thereafter,  however,  these 
conditions  are  reversed,  the  advancing  wave  causing  the  peripheral 
portion  to  become  distended,  while  the  more  central  portions  recoil 
and  bring  their  elastic  power  to  bear  upon  the  blood  within  them.  The 
pulse,  therefore,  is  essentially  a  reproduction  of  the  changes  in  pressure, 
modified  by  the  elastic  qualities  of  the  arterial  wall. 

Each  systole  of  the  heart  generates  a  certain  amount  of  energy 
which  is  transferred  in  part  to  the  arterial  wall  where  it  is  stored  as 
potential  energy,  to  be  made  use  of  subsequently  during  the  diastolic 
period  of  the  organ.  As  the  cardiac  energy  is  transmitted  at  regular 
intervals,  this  elastic  recoil  of  the  arteries  must  also  occur  at  regular 
intervals.  It  is  betrayed  externally  by  an  alternate  expansion  and 
shrinkage  of  the  arteries,  or  "pulse,"  which  is  most  manifest  near 


THE  PULSATORY  VAHIATIONS  IN  BLOOD  PRESSURE     379 

the  heart  and  fri-a(hially  IxM'omcs  less  apparent  in  the  direction  of  the 
distal  channels.  In  the  capillaries,  these  pulse  waves  arc  usually  not 
in  evidence,  because  the  friction  encountered  in  this  particular  division 
of  the  vascular  system  is  so  si'eat  that  th(^  fluctuations  in  pressure  are 
completely  neutralized.  But,  in  the  event  of  a  capillary  dilatation, 
this  resistance  is  usually  diniinishetl  to  such  an  extent  that  the  individ- 
ual pulsations  are  able  to  extend  directly  into  the  distahnost  veins. 
This  phenomenon  is  often  observed  in  glands  during  secretion,  because 
their  activity  necessitates  a  copious  supply  of  blood  and  hence,  an 
injected  state  of  their  capillaries.  In  the  submaxillary  gland,  this 
vasodilatation  may  be  produced  by  stimulation  of  the  chorda  tym- 
pani  nerve.  The  arterial  pulse  is  then  clearly  visible  in  the  small  vein 
draining  this  organ. 


Fig.   198. — Sphygmogram  from  the  Radl'VL  Artery,  Dudgeon  Sphygmograph. 
D,  the  dicrotic  wave;  P,  the  predicrotic  wave.      (Howell.) 

The  Frequency  of  the  Arterial  Pulse. — It  is  evident  that  the  number 
of  the  pulse-waves  must  coincide  precisely  with  the  frequency  of  the 
heart,  because  the  cardiac  output  forms  the  basis  of  these  oscillations. 
For  this  reason,  the  palpation  of  the  pulse  in  such  arteries  as  the  radial, 
brachial,  temporal,  or  carotid,  is  practised  primarily  for  the  purpose  of 
ascertaining  the  cardiac  frequency.  As  this  topic  has  been  dealt  with 
at  length  in  a  preceding  chapter,  it  need  not  be  discussed  further  at 
this  time.  Attention  should,  however,  be  called  to  one  or  two  pomts 
of  clinical  value. 

Under  certain  abnormal  conditions,  it  may  happen  that  some  of 
the  ventricular  contractions  do  not  develop  a  power  sufficient  to  raise 
the  semilunar  valve  flaps,  or,  if  they  do,  are  quite  unable  to  overcome 
the  general  arterial  pressure.  In  the  first  instance,  the  cardiac  efforts 
fail  absolutely  in  producing  pulse-waves,  and  in  the  second,  in  sus- 
taining them  for  any  considerable  distance.  This  is  generally  true  of 
the  so-called  extrasystoles  which,  as  the  name  indicates,  are  special 
contractions  interposed  between  the  regular  ones.  As  long  as  these 
extra  efforts  of  the  ventricles  do  not  interfere  with  the  general  rh3^hm 
and  output  of  the  heart,  no  circulatoiy  disturbances  result.  In  further 
illustration  of  this  fact,  that  the  frequency  of  the  pulse  does  not  always 
indicate  the  rate  of  the  heart,  might  be  mentioned  the  condition  of 
heart-block,  during  which,  as  has  been  stated  above,  the  auricular  rate 
is  maintained,  while  the  number  of  the  ventricular  contractions  is 
diminished.     Thus,  it  may  be  gathered  that  the  best  policy  is  to  bring 


380     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

the  arterial  pulse  into  relation  with  the  apex-beat,  as  well  as  with  the 
venous  pulse.  The  latter  is  jijcnerally  noted  in  the  region  of  the  cen- 
tral end  of  the  right  external  jugular  vein  and  is,  of  course,  indicative 
of  the  rate  of  the  auricles.  In  this  way  it  is  possible  to  detect  imme- 
diately any  dissociation  in  the  rhythm  of  the  heart. 

The  Velocity  of  the  Arterial  Pulse. — The  fact  that  the  pulse 
progresses  as  a  wave,^  may  readily  be  proved  by  the  simultaneous 
palpation  of  the  carotid  and  radial  arteries,  because,  as  the  former 
blood-vessel  lies  closer  to  the  heart,  the  characteristic  systolic  bump 
will  be  noted  sooner  here  than  in  the  latter  region.  The  interval, 
however,  is  so  brief  that  only  a  practised  observer  will  be  able  to  per- 
ceive it.  A  more  plastic  way  of  demonstrating  the  wave-like  character 
of  the  pulse  is  furnished  by  the  graphic  method.  Two  receiving  tam- 
bours which  in  turn  are  connected  with  two  recording  tambours,  are 
placed  upon  an  artery  at  different  distances  from  the  heart.  Upon 
being  permitted  to  record  in  the  same  vertical  line,  it  will  be  found 
that  the  lever  nearest  the  heart  is  always  raised  first,  and  naturally, 
the  difference  in  time  between  the  upstrokes  of  the  two  levers  is  the 
time  which  the  pulse-wave  requires  in  traversing  the  segment  of 
the  artery  situated  between  them.  Having  determined  this  distance, 
it  is  a  simple  matter  to  calculate  the  velocity  of  this  wave. 

While  it  may  be  said  that  the  rate  of  progression  of  the  pulse  is 
fairly  constant,  its  speed  must  differ  somewhat  from  moment  to 
moment,  because  the  conditions  in  the  vascular  system  are  subject 
to  frequent  changes.  This  is  especially  true  of  the  elastic  coefficient 
of  the  arterial  wall.  Thus,  it  may  be  inferred  that  its  velocity  in- 
creases whenever  the  arterial  pressure  is  raised  and  decreases  whenever 
the  latter  is  diminished.^  These  differences  may  readily  be  demon- 
strated by  the  repeated  stimulation  of  the  vagus  nerve  which  procedure 
is  followed  by  a  fall  in  pressure  incurred  by  the  diastolic  tendency  of  the 
heart.  For  very  similar  reasons  the  velocity  of  the  pulse  is  also  de- 
creased during  sleep  and  anesthesia.  The  difference  may  amount  to 
1  m.  per  second  and  more.  Concurrently,  it  may  be  reasoned  that  a 
lessening  of  the  distensibility  of  the  arteries  must  induce  a  greater 
velocity  of  this  wave.  A  condition  of  this  kind  arises,  for  example, 
during  arterio-sclerosis.  Landois,^  Edgren,'*  and  others  have  found 
values  ranging  between  6.5  and  9.0  m.  in  a  second.  The  arteries  used 
for  these  determinations  were  the  carotid  and  femoral  or  the  carotid 
and  radial.  It  has  also  been  noted  that  the  velocity  of  the  pulse  is 
somewhat  greater  in  the  blood-vessels  of  the  arm  than  in  those  arising 
from  the  descending  aorta.  It  seems  that  7  m.  per  second  may  be 
regarded  as  a  fair  average  value. 

^  Discovered  by  Erasistratus,  but  denied  by  Galenus.  It  remained  obscure 
until  the  time  of  Haller.  In  1850  E.  H.  Weber  made  the  first  attempts  to  deter- 
mine its  \'elocity. 

^  Moens,  Die  Pulskurve,  Leyden,  1878. 

^  Lehre  vom  Arterienpuls,  BerUn,  1872. 

^  Skand.  Archiv  fiir  Physiol.,  i,  1889,  67. 


THE  PULSATORY  VAHIATIONS  IN  BLOOD  PRESSURE     381 

In  this  connection  the  student  is  cautioned  against  confoundinji; 
the  velocity  of  the  pulse-wave  with  the  velocity  of  the  blood-stream. 
The  latter  is  seldom  greater  than  0.5  m.  in  a  second.  Thus,  a  stone 
thrown  into  a  river  produces  ripples  upon  its  surface  which  progress 
in  all  directions  with  a  speed  which  is  not  at  all  identical  with  that  of 
the  flow  of  this  body  of  water.  This  must  })e  so,  because  the  production 
of  a  current  necessitates  the  bodily  onward  movement  of  the  different 
particles  of  water  in  a  definite  direction,  while  a  ripple  merely  indicates 
the  passage  of  a  wave  incited  by  changes  in  the  p>osition  of  a  relatively 
small  number  of  these  particles.  The  wave,  therefore,  is  enabled  to 
attain  a  much  greater  speed  and  to  progress  even  against  the  stream. 
While  this  phenomenon  cannot  be  said  to  be  identical  with  the  arterial 
pulse,  the  stone  thrown  into  the  river,  really  plays  a  part  similar  to 
that  of  the  ventricular  discharge,  in  consequence  of  which  those  differ- 
ences in  pressure  are  established  which  give  rise  to  the  elastic  excursions 
of  the  arterial  wall.  A  much  better  way  of  proving  this  point  is  to  take 
a  fairly  long  piece  of  band-tubing  w^hich  is  connected  at  regular  dis- 
tances with  a  number  of  vertical  glass  tubes.  If  this  tubing  is  now 
filled  with  water  by  the  rhythmic  compression  of  a  rubber  bulb,  every 
addition  of  water  gives  rise  to  a  wave  which  may  easily  be  traced 
through  this  system,  because  it  induces  a  successive  oscillation  of 
the  fluid  in  the  different  collaterals. 

It  is  possible  to  ascertain  the  length  of  the  pulse-wave  by  multi- 
plying the  velocity  of  transmission  with  the  time  required  by  the  wave 
to  pass  a  certain  point.  The  former  value  is  7  m.  per  second  and  the 
latter  0.8  sec,  because  each  pulse- wave  occupies  the  time  of  a  cardiac 
cycle,  i.e.,  it  begins  with  the  systolic  discharge  and  ends  immediately 
before  the  succeeding  one.  The  value  so  found  is  5.6  m.  It  may  there- 
fore be  concluded  that  each  pulse  wave  arrives  at  the  periphery  of  the 
arterial  system  long  before  its  completion  at  its  point  of  origin  in  the 
aorta. 

The  Registration  of  the  Arterial  Pulse.  Sphygmography. — It  has 
previously  been  shown  that  the  cardiac  variations  in  arterial  pres- 
sure may  be  registered  without  difficulty  by  connecting  the  artery  with 
a  mercury  manometer.  It  is  true,  however,  that  the  minute  details 
of  these  oscillations  cannot  be  depicted  in  this  maimer,  because  the 
mercury  is  altogether  too  sluggish  to  follow  the  variations  in  pressure 
with  accuracy.  It  is  best,  therefore,  to  emploj'  a  membrane  manome- 
ter or  an  optical  manometer,  such  as  have  been  described  by  Hiirt.hle 
and  O.  Frank.  When  properly  dampened,  these  instruments  com- 
bine a  slight  inertia  with  an  exceptionally  high  speed  of  reaction. 

The  graphic  method  of  investigating  the  pulse  was  first  employed 
by  Vierordt^  in  1885,  but  the  instrument  which  he  devised  for  this 
purpose  is  not  well  suited  for  this  kind  of  work,  owing  to  its  relative 
inelasticity.     A  much  more  sensitive  instrument  has  been  constructed 

^  Lehre  vom  Arterienpuls,  Braunschweig,  1855. 


382     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

by  Marey/  to  which  the  name  of  sphygmograph  has  been  given. 
Although  variously  modified  in  subsequent  years,  the  principle  in- 
volved in  its  construction  has  not  been  changed. 

A  pellotte,  attached  to  a  steel  spring,  is  placed  upon  the  skin  over  the  radial 
artery  in  such  a  way  that  the  pulsations  of  this  blood-vessel  are  communicated 


Fig.  199. — Schema  Illustrating  the  Sphygmograph  of  Marey. 
B,  pelotte  applied  to  blood-vessel;   W,  toothed  wheel  fitting  into  toothed  rod;  R, 
the  up  and  down  movements  of  this  rod  give  rise- to  a  back  and  forth  movement  of  the 
wheel;    to   its   axis   is  attached  a  writing  lever  (L)  registering  its   excursions  upon  a 
kymograph  (K). 

to  it  directly.  But  as  the  excursions  executed  by  the  arterial  wall  and  over- 
lying tissues  are  relatively  small,  it  is  necessary  to  magnify  the  movements  of  the 
sphygmograph  considerably  by  increasing  the  leverage  of  its  writing  lever.  The 
latter  must  be  very  light  and  a  certain  resistance  must  be  imparted  to  it,  otherwise 


Fig.  200.  Fig.  201. 

Pig.  200. — The  Dudgeon  Sphygmograph  in  Position. 


Fig. 


201. — Diagram  Illustrating  the  Action  of  Dudgeon's  Sphygmograph. 

(Howell.) 
The  lever  of  the  Dudgeon  sphygmograph:  P,  the  button  of  the  spring 7^,  to  be  placed 
upon  the  artery.     The  movement  is  transmitted  to  the  lever,  Fi,  and  thence  to  the 
bent  lever,  F2,  the  movement  of  which  is  effected  through  the  weight,  g.     The  writing 
point  S,  of  this  lever  makes  the  record  on  the  smoked  surface,  A. 

its  movements  may  be  much  exaggerated  by  inertia.  In  the  instrument  of 
Czermak,  ^  the  place  of  the  recording  lever  is  taken  by  a  mirror  by  means  of  which 
a  beam  of  light  is  reflected  upon  sensitive  paper  moved  at  an  appropriate  speed. 

^  Jour,  de  la  physiol.,  iii,  1860. 

2  Sitzungsb.  der  Akad.  der  Wissensch.,  Wien,  1863. 


THE  PULSATORY  VARIATIONS  IN  BLOOD  PRESSURE  383 

Dudgeon  and  Jaquct^  havo  modified  this  instrument  by  addinp;  a  time  marker  and 
an  arrangement  l)y  means  of  whit-li  a  narrow  plate  of  hhu^kciicd  ^lass  is  moved 
past  the  rcconiing  needle.  But  as  the  length  of  this  recording  surface  must 
necessarily  be  limited,  it  does  not  permit  of  the  taking  of  long-continued  records. 
This  dLsadvantage  is  not  present  in  those  instruments  which  c^onsist  of  a  receiving 
and  a  recording  taml)our,  the  former  being  equipi)ed  with  a  button-like  pro- 
jection which  is  placed  directly  over  the  artery.^  As  the  n;cording  drum  of  this 
instrument  may  be  adjusted  to  a  kymograph  at  some  distance  from  the  artery, 
it  is  possiiile  to  obtain  long  and  uninterrupted  records.  The  so-called  angiometer 
of  Hiirthle  has  i)een  devised  to  register  the  pidsations  of  blood-vessels  when  fully 
exposed  to  the  view.  The  vessel  itself  is  held  in  a  metal  groove,  while  a  pellotte  is 
placed  upon  its  upper  border.  The  latter  is  connected  with  a  writing  lever  by 
means  of  a  .slender  rod. 

Character  of  the  Arterial  Pulse  Wave.     Sphygmogram. — Tho  curve 
recorded  bj'  a  sphyjj;inograph  is  designated  as  a  sphygmogram.     It 


A  C 

Fig.  202. — The  Character  of  the  Arterial  Pulse. 
AB,  anacrotic  limb;  BC,  catacrotic  limb;  B,  apex;  D,  dicrotic  wave;   N,  dicrotic 
notch;  E,  predicrotic  wave;  F,  postdicrotic    waves. 

gives  information  regarding  (a)  the  frequency,  (6)  the  rhythm, 
(c)  the  amplitude,  and  {d)  the  dicrotism  of  the  pulse.  Each  pulsation 
begins  with  an  ascent  which  is  the  counterpart  of  the  rise  in  systohc 
pressure.  Furthennore,  as  the  ventricle  discharges  its  contents  rather 
quickly,  this  upstroke  must  necessarily  be  steep.  The  curve  attains 
its  greatest  height  at  the  point  of  greatest  distention  of  the  artery, 
forming  here  the  so-called  apex.  It  then  declines  slowly  until  the 
following  systole  of  the  heart  again  sends  it  abruptly  upward.  In 
contradistinction  to  the  almost  vertical  upstroke,  the  downstroke 
slants  considerably,  because,  being  opposed  by  a  high  capillary  re- 
sistance, the  recoil  of  the  distended  arteries  cannot  give  rise  to  a  per- 
fectly free  escape  of  blood  into  the  capillaries  and  veins.  Each  wave 
of  the  pulse,  therefore,  consists  essentially  of  two  phases,  its  ascending 
portion  being  designated  as  the  anacrotic  limb,  and  its  descending  por- 
tion as  the  catacrotic  limb. 

Keeping  these  facts  clearly  in  mind,  we  are  now  in  a  position  to 
consider  some  of  its  minor  details   (Fig.   202).     The  anacrotic  limb 

1  Zeitschr.  fiir  Biologie,  xxviii,  1891.  A  description  of  the  sphygmograph  of 
Fetter  and  Frank  is  given  in  this  Journal,  xlix,  1907,  70. 

^  Brondgeest,  Onderz.  gedaan  in  het  physiol.  Lab.  d.  Utrecht.  Derde  Reeks, 
ii,  1873. 


384     THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

(A-B)  is  generally  smooth;  its  steepness,  however,  varies  with  the 
tension  prevailing  in  the  arteries.  If  the  pressure  is  high,  the  ascent 
must  be  slower,  because  it  is  then  developed  against  a  greater  resist- 
ance. A  low  pressure,  on  the  other  hand,  favors  a  more  rapid  rise  in 
pressure  and  hence,  also  the  production  of  a  more  vertical  anacrotic 
limb.  It  should  also  be  remembered  that  if  the  resistance  in  the  arterial 
system  is  high,  the  upstroke  frequently  shows  certain  secondary  waves 
which  indicate  the  occurrence  of  an  elastic  quivering.  Conditions  of 
this  kind  are  encountered  in  arteriosclerosis  and  stenosis  of  the  semi- 
lunar valves.  These  extra  oscillations  which  are  generally  situated 
near  the  apex  of  the  curve,  are  known  as  anacrotic  waves.  In  accord- 
ance with  the  preceding  statement,  it  may  be  assumed  that  they  are 
tension-waves,  i.e.,  quick  reflections  from  the  periphery.  This  view 
was  first  expressed  by  v.  Kries,^  who  produced  them  in  the  radial  artery 
by  raising  the  hand  to  such  a  level  that  the  static  effects  permitted  the 
occurrence  of  reflections  from  the  periphery  before  the  summit  of  the 
pulse-curve  had  been  reached.  Obviously,  any  condition  which  hin- 
ders the  quick  emptying  of  the  ventricles,  must  give  sufficient  time  for 
these  reflections  to  develop.  They  are  especially  prone  to  occur  in 
aortic  stenosis  when  the  narrowing  of  the  aortic  orifice  is  associated 
with  a  hypertrophy  of  the  ventricular  musculature. 

The  apex  (B)  of  the  normal  pulse-wave  possesses  a  rounded  out- 
line, while  in  the  sphygmogram  it  is  generally  very  pointed.  This 
discrepancy  must  be  attributed  to  an  instrumental  error,  namely,  to 
the  "fling"  which  is  imparted  to  the  lever  and  its  connecting  parts 
whenever  the  artery  is  suddenly  expanded.  When  especially  conspicu- 
ous it  is  called  the  "percussion-wave." 

The  catacrotic  limb  (B-C)  exhibits  several  details  which  deserve 
a  more  lengthy  discussion.  Its  most  constant  characteristic  is  a 
well-marked  secondary  rise  which  appears  near  the  middle  of  the  de- 
scent and  is  known  as  the  dicrotic  wave  (D).  Subsequent  to  this  point 
a  number  of  smaller  wavelets  are  usually  observed  which  are  desig- 
nated as  the  postdicrotic  waves  (F).  Immediately  preceding  the  di- 
crotic wave,  a  small  oscillation  is  generally  obtained  which  is  called 
the  predicrotic  wave  (E).  Between  points  E  and  F,  the  curve  shows 
a  depression,  known  as  the  dicrotic  notch  {n). 

While  the  dicrotic  character  of  the  pulse  was  recognized  by  pal- 
pation long  before  the  invention  of  the  sphygmograph,  its  dicrotism 
was  first  demonstrated  in  a  plastic  manner  by  Thelius  in  1850.^  Some- 
time later  Marey^  obtained  graphic  records  of  it,  while  Landois* 
proved  its  existence  by  pricking  an  artery  with  a  needle  and  by  permit- 
ting the  blood  to  spurt  against  the  paper  of  a  slowly  revolving 
kymograph.     Records  of  this  kind  are  called  hematograms. 

1  Studien  zur  Pulslehre,  1892. 

^  Vierteljahrschr.  f iir  prakt.  Heilkunde,  xxi,  1850. 

'  Jour,  de  la  Physiol.,  iii,  1860. 

*  Pfluger's  Archiv,  ix,  1874. 


THE  PULSATORY  VARIATIONS  IN  BLOOD  PRESSURE  385 

A  pronouncod  dit'iotisin  of  tlio  pulse  usu:illy  indicates  ji  low  blood 
pressure,  l)ec'ause  a  low  tension  permits  the  systolic-diastolic  differences 
and  other  fluctuations  in  pressure  to  become  extreme.  Ck)nditions 
of  this  kind  frequently  develop  in  the  course  of  many  wasting  diseases, 
and  especially  during  fevers,  such  as  typhoid,  when  a  low  peripheral 
resistance  is  associated  with  an,  as  yet,  efficient  pumping  force  of  the 
heart.  Any  factor,  therefore,  which  induces  sudden  and  extreme 
variations  in  pressure,  or  favors  the  elastic  resiUency  of  the  arterial 
wall  must  tend  to  augment  the  dicrotism.  For  this  reason,  it  is 
usually  very  conspicuous  in  young  people,  but  not  in  adults  and 
older  persons,  because  their  arteries  have  been  rendered  more  rigid  by 
calcareous  infiltration. 

Any  discussion  as  to  the  cause  of  the  dicrotic  wave  must  first  of  all 
take  into  account  that  it  may  be  a  reflection  traveling  from  the  heart 
outward,  or  that  it  may  be  a  peripheral  reflection  passing  inward.  The 
second  possibility  may  be  disposed  of  very  quickly,  because  if  it  really 
were  a  centripetal  wave,  it  should  be  possible  to  obtain  it  apart  from 
the  principal  wave  of  the  pulse.  The  latter  has  been  proven  to  be  of 
central  origin.  Now,  since  the  dicrotic  elevation  always  keeps  at  a 
definite  distance  from  the  apex  of  the  primary  wave,  we  are  entirely 
justified  in  concluding  that  it  originates  centrally  and  represents, 
therefore,  a  centrifugal  wave,  traveling  at  the  same  velocity  as  the 
principal  one. 

Having  established  the  direction  of  the  dicrotic  wavelet,  it  now 
becomes  a  relatively  simple  matter  to  detect  its  cause.  As  may 
readily  be  surmised,  the  latter  must  be  sought  in  the  closure  of  the 
semilunar  valves.  A  thorough  distention  of  the  aorta  having  been 
attained,  its  walls  recoil  immediately  upon  the  completion  of  the  ventric- 
ular systole  and  place  the  blood  within  under  continued  pressure.  The 
blood  then  seeks  to  escape  in  the  direction  of  least  resistance,  namely, 
toward  the  capillaries  as  well  as  toward  the  heart.  The  centripetal 
movement  of  the  column  of  blood  is  at  first  greatly  facilitated  by  the 
negativity  resulting  in  the  root  of  the  aorta  in  consequence  of  the 
ventricular  discharge,  but  is  suddenly  cut  short  by  the  approximation 
of  the  aortic  semilunar  valve-flaps.  Being  thus  suddenly  thrown 
against  the  closed  semilunar  valve,  a  reflection  results  which  is  con- 
veyed toward  the  periphery  in  the  form  of  a  wavelet  superimposed  upon 
the  principal  wave. 

The  dicrotic  notch  immediately  preceding  the  dicrotic  elevation, 
seems  to  have  its  origin  in  the  decrease  in  pressure  resulting  in  the  root 
of  the  aorta  at  the  beginning  of  ventricular  diastole.  As  the  aortic 
walls  recoil  and  force  the  blood  against  the  closed  semilunar  valves, 
a  slight  downward  deviation  of  the  latter  results,  because  they  are 
no  longer  supported  by  the  firmly  contracted  ventricular  musculature. 
This  yielding  of  the  "semilunar  floor,"  however,  is  very  limited  and 
soon  gives  way  to  a  rebound  of  the  blood  which  in  turn  causes  the 
distention  of  the  aorta  described  a  moment  ago  as  the  dicrotic  wave. 

25 


386    THE    MECHANICS    OF   THE    CIRCULATION,    HEMODYNAMICS 

The  predicrotic  wave  or  waves  appear  to  be  exaggerations  of  the 
recoil  produced  by  the  "fling"  of  the  writing  lever,  but,  contrary 
to  the  inertia  which  gives  rise  to  the  pointed  apex,  or  percussion-wave, 
these  secondary  elevations  are  not  dependent  upon  the  initial  upward 
throw  of  the  lever,  but  upon  its  rebound  as  it  again  endeavors  to  as- 
sume the  resting  position.  These  oscillations,  however,  are  destroyed 
very  shortly  by  the  negative  variation  appearing  in  the  form  of  the 
dicrotic  notch.  The  postdicrotic  wavelets  have  also  been  regarded 
as  inertia  movements  of  the  instrument.  It  is  more  than  probable 
that  the  dicrotic  elevation  suffers  an  exaggeration  in  the  same  way  as 
the  primary  wave  and  hence,  the  writing  lever  and  its  connecting  parts 
can  assume  their  position  of  rest  only  after  they  have  passed  through 
several  adj  usting  oscillations.  Another  view  is  that  they  represent  after- 
vibrations  of  the  column  of  blood  following  in  the  wake  of  the  dicrotic 
wave. 

It  should  also  be  remembered  that  the  tracings  of  the  pulse  taken 
from  different  arteries,  show  certain  differences  regarding  these  minor 
fluctuations.  In  explanation  of  this  phenomenon  it  has  been  suggested 
by  Frank^  that  certain  regions  of  the  vascular  system  are  so  shaped  that 
they  are  capable  of  giving  rise  to  special  types  of  reflections  which  then 
tend  to  modify  the  character  of  the  principal  pulse-wave.  Thus,  it 
has  been  stated  that  the  carotid  pulse  is  influenced  by  waves  reflected 
from  the  circle  of  Willis,  while  the  pulse  in  the  descending  aorta  suffers 
a  sHght  modification  in  consequence  of  reflections  from  the  bifurca- 
tion of  the  iUac  arteries.  It  is  true,  however,  that  many  of  these 
secondary  currents  interfere  with  one  another  in  such  a  way  that  they 
become  neutralized. 

Pulse  Pressure. — When  referring  to  blood  pressure,  we  usually 
have  its  average  value  in  mind.  It  has  been  pointed  out  above  that 
this  value  may  be  determined  most  accurately  by  ascertaining  the 
arithmetic  mean  of  the  systoUc  and  diastolic  pressures,  as  registered 
by  the  direct  method.  It  may  also  be  determined  by  the  indirect 
method,  but  only  approximately,  because  this  estimate  must  be  based 
upon  the  diastolic  pressure.  The  mean  pressure  follows  the  diastoUc 
minimum  pressure  more  closely  than  the  systohc  maximum  and  hence,  a 
greater  importance  is  frequently  attached  to  the  former  than  to  the 
latter.  But  as  a  definite  numerical  relationship  between  these  factors 
does  not  exist,  the  average  blood  pressure  is  usually  determined  in  a 
rough  way  by  adding  one-third  of  the  systolic-diastoHc  difference  to 
the  diastoUc  pressure.  It  has  also  been  estimated  at  75  per  cent,  of  the 
systoUc  pressure. 

The  systoUc-diastohc  difference  in  blood  pressure  is  generally  desig- 
nated as  the  pulse  pressure.  Thus,  if  a  systolic  value  of  130  mm. 
Hg  is  opposed  by  a  diastohc  value  of  90  mm.  Hg,  the  pulse  pressure 
equals  40  mm.  Hg.  Keeping  this  fact  clearly  in  mind,  the  changes 
which  the  pulse-pressure  may  undergo  need  not  be  considered  in 
1  Tigerstedt,  Ergebn.  der  Physiol,  viii,  1909. 


THE  PULSATORY  VARIATIONS  IN  BLOOD  PRESSURE  387 

detail,  because  they  are  identical  with  those  exhibited  l)y  the  systolic 
and  diastolic  pressures  indivichially.  It  may  therefore  be  said  that 
it  is  subject  to  alterations  in  (a)  the  energy  of  the  heart,  (6)  the 
peripheral  resistance,  (c)  the  elasticity  of  the  blood-vessels,  and  (d) 
the  quantity  of  tiie  circulating  ])l()od. 

The  Clinical  Significance  of  the  Sphygmogram. — The  information 
to  be  derived  from  a  study  of  tiie  spliygmogram  is  of  slight  clinical 
value.  No  doubt,  if  properly  adjusted,  the  sphygmograph  may  serve 
as  an  accurate  means  for.  determining  the  frequency  and  rhythm  of  the 
heart,  although  it  does  not  permit  us  to  draw  definite  conclusions  re- 
garding the  dynamical  conditions  prevailing  in  the  vascular  system. 
In  the  first  place,  the  length  of  the  individual  pulse-waves,  as  well  as 
their  general  character,  may  be  varied  considerably  by  technical  (errors 
committed  in  adjusting  the  instrument.  Thus,  it  is  of  ten  difficult  to 
apply  it  with  that  degree  of  pressure  which  is  required  to  counter- 
balance the  sj^stolic  pressure.  In  the  second  place,  it  must  be  granted 
that  the  excursions  of  the  instrument  depend  in  a  large  measure  upon 
the  thickness  of  the  tissues  overlying  the  artery  and  upon  the  degree 
of  injection  of  the  neighboring  veins.  It  is  best,  therefore,  to  regard 
the  sphygmograph  merely  as  an  aid  to  diagnosis  and  to  draw  no  rigid 
conclusions  from  its  records.  It  is  much  easier,  and  also  much  safer, 
to  base  your  deductions  upon  the  methods  of  inspection  and  palpation, 
because  by  these  means  the  frequency  and  regularity  of  the  heart  are 
made  evident  in  a  much  more  direct  manner.  In  addition,  these 
simple  methods  enable  us  to  estimate  the  general  character  of  the 
pulse-wave,  and  hence,  also  the  tension  prevailing  in  the  arterial,  sys- 
tem and  the  efficiency  of  the  entire  circulatory  mechanism.  The  fol- 
lowing qualitative  differences  are  generally  ascribed  to  the  pulse: 

(a)  Frequens  or  Rarus. — A  pulse  is  characterized  as  quick  if  it  surpasses  the 
normal  maximum  and  as  slow  if  it  falls  below  the  normal  minimum.  For  men, 
these  limits  lie  respectively  at  75  and  68  beats  in  a  minute. 

(6)  Celer  or  Tardus. — Attention  should  first  be  called  to  the  fact  that  these 
terms  do  not  refer  to  the  frequency  of  the  pulse,  but  solely  to  the  speed  with  which 
the  indi\'idual  waves  are  developed.  Their  rise  and  fall  may  be  quicker  or  slower 
than  normal.  Pulses  of  the  first  type  indicate  either  a  relaxed  condition  of  the 
vascular  system,  a  quick  escape  of  the  arterial  blood,  or  an  undue  brevity  and  slight 
force  of  the  ventricular  contraction.  An  especially  pronounced  pidse  of  this  kind 
is  present  in  aortic  regurgitation,  because  the  incompetency  of  this  valve  permits 
of  a  quick  escape  of  arterial  blood  into  the  heart.  A  tardy  pulse  is  obtained 
whenever  the  ventricular  discharges  encounter  a  high  peripheral  resistance. 

(c)  Magnus  or  Parvus. — These  terms  are  used  to  describe  the  ampUtude  or 
volume  of  the  different  pulse-waves.  A  third  term,  namely,  pulsus  inequalis,  is 
employed  to  show  that  the  successive  waves  are  unequal  in  their  volimie. 

(d)  Durus  or  Mollis. — These  qualities  of  the  pulse  are  independent  of  the 
condition  of  the  arterial  wall  and  are  indicative  of  the  tension  prevailing  in  the 
arterial  channels.  If  an  undue  force  must  be  employed  to  compress  the  artery 
sufficiently  to  cause  the  disappearance  of  the  pulse,  it  is  characterized  as  hard. 
If  it  is  readily  obliterated,  it  is  said  to  be  soft. 

(e)  Intermittens  or  Deficiens. — -Disturbances  in  the  rhythm  of  the  pulse 
result  either  in  consequence  of  weak  contractions  of  the  heart  or  in  consequence  of 


388    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

an  occasional  intermittency.  If  the  former,  the  pulse  is  characterized  as  inter- 
mittent, and  if  the  latter,  as  deficient.  Clearly,  the.  absence  of  the  pulse  in  a 
peripheral  blood-vessel  does  not  signify  that  it  is  also  absent  near  the  heart  or  that 
the  cardiac  contractions  have  ceased  altogether. 

(J)  Intercurrens,  Alternans,  and  Bigeminus. — These  types  of  pulses  also  indi- 
cate a  disturbance  in  the  cardiac  rhythm.  If  an  occasional  wave  is  forced  in 
between  two  regular  ones,  the  pulse  is  said  to  be  intercurrent.  Its  cause  must 
be  sought  in  extra  systoles.  A  true  alternating  pulse  consists  of  rhythmic  waves 
of  large  and  small  amplitude,  this  abnormality  being  usually  dependent  upon  a 
degeneration  of  the  myocardium.  The  prognosis,  therefore,  is  grave.  An  en- 
tirely different  significance,  however,  must  be  attached  to  the  pseudo-alternating 
pulse  and  the  pulsus  bigeminus.  As  these  types  of  pulses  are  dependent  upon 
extrasystoles,  two  waves  must  necessarily  appear  at  the  periphery  whenever  an 
additional  contraction  results,  but  the  wave  produced  by  the  extra  contraction 
is  always  smaller  than  the  normal  one.  In  the  bigeminus  variety  the  pulse-waves 
appear  in  couplets,  i.e.,  the  normal  and  succeeding  extra  waves  are  separated  from 
the  neighboring  ones  by  a  definite  interval.  In  the  pseudo-alternating  pulse,  on 
the  other  hand,  this  separation  is  not  clearly  in  evidence,  because  it  is  caused  by 
extra  systoles  of  the  premature  type. 

B.  THE  CARDIAC  VARIATIONS  IN  VENOUS  BLOOD  PRESSURE 

The  Physiological  Venous  Pulse.^ — ^The  venous  entrances  to  the 
heart  are  not  guarded  by  valves;  moreover,  while  the  size  of  these 
orifices  is  greatly  lessened  during  systole  in  consequence  of  the  con- 
traction of  the  circular  layer  of  muscle  fibers,  their  complete  closure 
is  not  effected.  For  this  reason  it  cannot  surprise  us  to  find  that  the 
auricular  pressure  is  propagated  outward  into  the  central  veins,  where 
it  influences  the  venous  pressure  as  well  as  the  flow.  Thus,  if  a  water- 
manometer  is  connected  with  a  central  vein,  the  level  of  the  water 
immediately  exhibits  rhythmic  fluctuations  which  occur  synchronously 
with  the  contractions  of  the  heart.  In  addition  to  these  oscillations 
it  also  shows  much  larger  wave-like  variations  which  are  dependent 
upon  the  respiratory  movements.  The  finer  details  of  these  waves 
may  be  brought  out  more  clearly  by  registering  them  with  the  help 
of  a  membrane  manometer. 

The  cardiac  variations  in  venous  pressure  are  most  manifest  near 
the  heart  and  gradually  decrease  in  amplitude  in  the  direction  of  the 
peripheral  veins.  They  are  usually  absent  from  the  abdominal 
portion  of  the  inferior  vena  cava  as  well  as  from  the  distal  end  of  the 
external  jugular  vein,  but  their  presence  in  these  channels  depends 
very  largely  upon  the  force  of  the  heart  beat  and  the  tension  prevailing 
throughout  the  venous  system.  These  changes  in  pressure  give  rise  to 
pulsations  which  are  generally  obtained  from  the  external  jugular  vein 
in  close  proximity  to  the  aperture  of  the  chest.  Distally  to  this  point 
they  are  usually  so  slight  that  they  cannot  be  properly  registered. 
Tracings  of  the  venous  pulse  may  also  be  obtained  from  the  central 
veins  of  animals  after  the  chest  has  been  opened.  A  receiving  and  a 
recording  tambour  are  commonly  employed  for  this  purpose.  This 
record  is  known  as  a  phlebogram. 


THE   PULSATORY  VARIATIONS  IX  RLOOD   PRESSURE  389 

The  Speed  and  Character  of  the  Physiological  Venous  Pulse. — In 

agreement,  with  the  low  tension  prevaihntz;  in  the  venous  system,  the 
physiolofjiical  venous  pulse  does  not  attain  a  considerable  velocity. 
IVIorrow'  states  that  it  is  only  1-3  m.  in  a  second.  A  study  of  its 
genera]  outline  shows  that  it  consists  of  three  undulations  (Fig.  203). 
In  accordance  with  Fredericq,-  the  initial  elevation  (^4)  is  caused  by  the 
contraction  of  the  auricle,  the  wave  of  high  intra-auricular  pressure 
being  propagated  into  the  veins.  The  second  positive  wave  (C) 
is  due  to  ventricular  systole,  because  the  auriculoventricular  valves 
are  forced  upward  and  thus  encroach  upon  the  space  of  the  auricles. 
The  third  rise  (F)  is  dependent  upon  a  reflection  caused  by  the  rapid 
infliLx  of  venous  blood  into  the  passive  auricles.  If  this  explanation 
is  accepted,  and  it  seems  to  be  the  most  feasible  one,  the  physiological 
venous  pulse  is  to  be  regarded  as  the  counterpart  of  the  curve  of  intra- 
auricular  pressure,  the  latter  being  propagated  outward  into  the  central 


Fig.  203. — Dl\gr.\mmatic  Representation  of  the  Physiol.  Venols  Pulse  from  the 
Central  Ent)  of  the  Ext.  Jugular  Vein. 
A,  a-wave;  C,  c-wave;  V,  ■w-wave. 

venous  chaAnels  through  the  incompetent  caval  and  pulmonary 
orifices.  The  a-wave  is  generally  the  largest,  but  if  it  should  prove 
difficult  at  any  time  to  differentiate  these  summits  from  one  another, 
it  is  advisable  to  identify  the  c-wave  first  of  all.  This  is  a  simple 
matter,  because  it  merely  involves  the  determination  by  auscultation 
or  palpation  of  the  onset  of  ventricular  systole.  For  this  reason,  it  is 
always  safest  to  record  the  venous  pulse  in  conjunction  with  the  arterial 
pulse  or  the  apex-beat. 

In  accordance  with  the  view  presented  by  Mackenzie,^  the  changes 
in  intra-auricular  pressure  should  not  be  regarded  as  the  sole  cause 
of  the  venous  pulse,  because  its  real  character  is  more  directly  deter- 
mined by  the  pulsations  occurring  in  the  blood  current  of  the  neighbor- 
ing carotid  artery.  If  we  follow  the  usual  custom  of  designating 
the  three  elevations  of  the  venous  pulse  as  the  a,  c  and  v  waves,  it 
becomes  evident  that : 

1.  The  a-wave  is  dependent  upon  the  outward  propagation  of  the  principal 
elevation  of  the  intra-auricular  pressure  and  is  caused,  therefore,  by  the  contrac- 
tion of  the  auricle. 

2.  The  c-wave  is  not  identical  with  the  second  rise  in  the  intra-auricular  pressure 
caused  by  the  systolic  elevation  of  the  auriculoventricular  system,  but  is  occa- 
sioned by  the  transfer  of  the  pulse  from  the  neighboring  carotid  artery. 

1  Pfliiger's  Archiv,  Ixxix,  1900,  412. 

2  Centralbl.  fiir  Physiol,  xxii,  1908. 

'Study  of  the  Pulse,  London,  1912;  also  see:  Lev.-is,  Mechanism  of  the  Heart 
Beat,  London,  1911. 


390    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

3.  The  v-wave  appears  normally  from  0.1  to  0.2  second  after  the  commence- 
ment of  the  a-wave  and  finds  its  origin  in  the  pressure  changes  resulting  from 
ventricular  systole. 

In  view  of  the  fact  that  the  c-wave  appears  in  the  external  jugular 
vein  before  the  corresponding  cardiac  impulse  has  had  sufficient  time  to 
make  itself  felt  in  the  carotid  artery,  it  seems  that  this  explanation  of 
Mackenzie  cannot  be  correct.  In  this  connection  it  should  also  be 
remembered  that  a  venous  pulse  is  present  in  the  pulmonary  veins, 
and  that  its  cause  is  precisely  the  same  as  that  producing  these  pulsa- 
tions in  the  systemic  veins. 

The  Pathological  Venous  Pulse. — This  phenomenon  is  most  com- 
monly associated  with  an  incompetency  of  the  tricuspid  valve,  but  may 
also  appear  in  the  pulmonary  vein  in  consequence  of  mitral  regurgita^ 
tion.  It  may  be  surmised  that  this  regurgitation  of  the  blood  into  the 
auricle  gives  rise  to  a  much  larger  c-wave  than  the  normal  upward 

movement  of  the  auriculoventricular 
'^..-•>.  septum  could  possibly  produce.     In 

fact,  a  severe  insufficiency  often  in- 
creases the  amplitude  of  this  wave 
so  greatly  that  it  completely  over- 
laps the  a-wave.     Under  this  condi- 
tion, the  phlebogram  presents  only 
Fig.  204.— Diagram.\l\tic  Representa-  one  large  initial  rise  which  is  followed 
TiON  OF  TEiE  Path.  Venous  Pui^e.        ^^   ^   ^^^^^^^   ^^^^   previously    desig- 
In  tricuspid  regurgitation  the  C  wave  is  j.    j  .-i  t^  j.    u 

very  much  increased.  ^ated   as  the   y-wave.     It  must  be 

evident  that  the  conspicuousness  of 
the  pathological  venous  pulse  must  differ  with  the  severity  of  the 
valvular  lesion,  a  severe  regurgitation  increasing  the  radius  of  these 
pulsations  so  that  they  may  be  perceived  even  in  the  distalmost  veins. 
The  venous  engorgement  always  accompanying  the  regurgitation 
eventually  produces  a  hyperemic  condition  of  different  organs  and 
preeminently  of  the  hver.  It  is  then  possible  to  obtain  these  pulsa- 
tions directly  from  this  organ  by  applying  a  flat  metal  cup  to  the  skin 
overlying  it,  but  naturally,  the  minute  details  of  the  individual  waves 
are  difficult  to  record,  because  the  intervening  mass  of  tissue  does  not 
readily  transmit  the  rapid  oscillations  in  pressure.  A  third  type  of 
venous  pulse  is  observed  at  times  in  the  veins  of  glands,  but  only 
when  the  latter  are  actively  secreting.  These  pulsations  are  nothing 
more  than  the  arterial  pulse  propagated  through  the  highly  distended 
capillaries  of  the  gland. 

C.  THE  RESPIRATORY  VARIATIONS  IN  ARTERIAL  AND  VENOUS  BLOOD 

PRESSURE 

The  General  Character  of  the  Respiratory  Variations. — Besides 

the  small  cardiac  oscillations,  the  blood  pressure  also  exhibits  fluctua- 
tions of  a  much  larger  amplitude  which  occur  synchronously  with  the 


THE  PULSATORY  VARIATIONS  IN  RLOOD  PRESSURE 


391 


respiratory  movements.  It  is  to  be  noted  that  inspiration  produces  a 
fall  in  pressure  in  the  veins  and  a  rise  in  th(>  arteries,  whereas  expiration 
causes  an  increase  in  the  venous  and  a  fall  in  the  arterial  pressure  (Fig. 
205).  These  changes  are  generally  associated  with  an  alteration  in  the 
cardiac  rhyt.hm,  the  heart  beating  more  frequently  during  inspiration. 
Moreover,  these  fiuetuations  do  not  begin  precisely  with  the  onset  of 
the  respiratory  movements,  but  somewhat  later,  the  intervening  period 
being  about  0.2  second  in  duration.  It  happens,  therefore,  that  the 
arterial  rise  is  always  continued  for  a  brief  period  of  time  after  the  be- 
giiming  of  the  expiratory  motion,  while  the  fall  is  prolonged  right  into 
the  succeeding  inspiratoiy  phase. 

The  Cause  of  the  Respiratory  Variations. — After  the  first  breath 
has  been  taken,  the  lungs  are  held  in  a  continuous  state  of  hyperdisten- 
tion.  The  elastic  fibers  contained  in  them  are  put  on  the  stretch  and 
must  therefore  always  attempt  to  recoil.  This  enables  these  organs  to 
exert  an  elastic  pull  upon  the  chest  wall  as  well  as  upon  the  contents  of 


A?^ 


Fig.  205. — Diagrammatic  Representation  of  the  Respiratory  Variations  in  Arterial 
(AP)  AN-D  Venous  Pressure  (VP). 
JE,  inspiration;  EJ ,  expiration.      It  is  to  be  noted  that  the  variations  in  pressure 
lag  behind  the  onset  of  the  respiratory  movement;  this  interval  {JB)  being  especially 
evident  in  the  case  of  the  arterial  pressure. 

the  thoracic  cavity,  which  is  betrayed,  on  the  one  hand,  by  a  nega- 
tivity in  the  intrapleural  pressure  (-6  to  -9  mm.  Hg)  and,  on  the 
other,  by  the  low  degrees  of  pressure  existing  in  the  central  venous 
system  (-5  to  -15  mm.  Hg).  The  blood-vessels  situated  outside 
the  thorax  are  exposed  to  positive  pressures,  and  hence,  it  cannot 
surprise  us  to  find  that  the  blood  in  the  intrathoracic  vessels  is  con- 
stantly exposed  to  this  aspiratory  force.  But  inasmuch  as  the  ar- 
teries are  relatively  resistant  and  unyielding,  they  are  not  so  severely 
affected  as  the  veins. 

It  must  be  granted,  therefore,  that  the  negative  pressure  in^  the 
thorax  favors  the  venous  return.  Moreover,  as  the  elastic  pull  upon 
the  venous  trunks  is  greater  during  inspiration  than  during  expiration, 
the  inspiratoiy  movement  must  be  the  more  effective  of  the  two.  For 
this  reason,  it  is  only  natural  to  assume  that  the  venous  pressure  is 
decreased  during  inspiration  and  increased  during  expiration.  It 
may  be  inferred  that  these  changes  in  pressure  influence  the  flow  in 


392    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

such  a  way  that  a  greater  quantity  of  blood  is  drawn  into  the  central 
venous  channels  during  inspiration  than  during  expiration.  Conse- 
quently, as  the  heart  receives  more  blood  during  the  former  period,  it 
is  in  a  position  to  pump  more  blood  into  the  arteries.^  This  explains 
the  inspiratoiy  rise  in  arterial  pressure.  This  mechanical  explanation 
of  the  respiratory  variations  finds  support  in  the  following  conditions: 

(c)  It  has  already  been  stated  that  the  heart  increases  its  frequency  during 
inspiration.  This  phenomenon  may  be  explained  in  two  ways.  Thus,  it  may  be 
assumed  that  it  is  a  reflex  elicited  within  the  heart  in  consequence  of  the  influx 
of  a  greater  quantity  of  blood,  or  that  it  is  due  to  accelerator  impulses  generated 
by  the  cardiac  center.  The  latter  explanation  has  been  submitted  by  Fredericq, 
who  has  found  that  this  acceleration  takes  place  even  after  the  mechanical  in- 
fluence of  respiration  upon  the  heart  has  been  removed  by  opening  the  chest. 
The  fact  that  the  division  of  the  vagi  nerves  destroys  the  acceleration  immediately 
proves  that  this  system  is  directly  concerned  with  the  production  of  this  phe- 
nomenon. It  is  also  interesting  to  note  that  this  acceleration  is  more  marked  in 
persons  whose  nervous  system  is  in  a  state  of  hyperirritability. 

(6)  The  transfer  of  blood  from  the  right  into  the  left  side  of  the  heart  is  greatly 
facilitated  by  inspiration,  because  this  movement  permits  of  a  greater  distention 
of  the  pulmonary  blood-vessels,  thereby  lessening  the  resistance  in  this  circuit. 
During  expiration,  on  the  other  hand,  the  elastic  pull  upon  these  vessels  is  dimin- 
ished and  the  resistance  within  them  increased. 

(c)  The  inspiratory  descent  of  the  diaphragm  favors  the  venous  return  from 
the  abdominal  organs,  because  it  tends  to  increase  the  pressure  in  the  abdominal 
cavity  and  to  lessen  the  resistance  in  the  thorax.^ 

(d)  The  fact  that  these  changes  may  be  rendered  more  conspicuous  by  in- 
creasing the  amplitude  of  the  respiratory  movements  is  another  point  in  favor 
of  this  explanation.  Last  of  all,  it  should  be  taken  into  account  that  these  varia- 
tions are  completely  reversed  during  artificial  respiration.*  This  need  not  cause 
surprise,  because  the  artificial  inflation  of  the  lungs  induces  conditions  practically 
the  reverse  of  those  prevailing  during  normal  respiration,  when  this  organ  is  ex- 
panded by  a  force  resting  upon  its  external  surface.  As  the  air  is  forced  into  the 
pulmonary  passage,  the  capillaries  of  the  lungs  are  subjected  to  a  certain  pressure 
which  tends  to  increase  the  resistance  within  them.  This  implies  that  the  venous 
pressure  is  increased  during  the  period  of  inflation,  whereas  the  influx  of  blood  is 
diminished.  The  deflation  of  the  lungs,  on  the  other  hand,  relieves  this  com- 
pression of  the  pulmonary  capillaries  and  permits  a  more  unhindered  through- 
flow  in  consequence  of  the  diminution  in  the  resistance. 

As  has  been  emphasized  by  Wiggers,^  the  respiratory  variations  in 
blood  pressure  may  be  explained  without  difficulty  upon  the  basis  of 
the  circulatory  changes  in  the  lesser  circuit  just  enumerated.  Lewis,^ 
on  the  other  hand,  believes  that  the  respiratory  motions  affect  the 
heart  in  a  direct  way,  and  that  the  effect  upon  the  arterial  blood 
pressure  varies  with  the  type  of  respiration.  Thus,  diaphragmatic  res- 
piration is  said  to  give  an  inspiratory  rise  and  expiratory  fall  in  ar- 
terial pressure,  while  a  pronounced  costal  movement  induces  an  inspira- 
tory fall  and  expiratory  rise.     This  result,  however,  is  easily  explained 

1  Burton-Opitz,  Am.  Jour,  of  Physiol.,  vii,  1902,  435. 

2  Burton-Opitz,  ibid.,  xxxv,  1914,  64. 

3  Burton-Opitz,  ibid.,  ix,  1903,  198. 
*  Ibid.,  xxxv,  1914. 

6  Ibid.,  xvi,  1906. 


THE    PULSATORY   VARIATIONS    IN    HLOOD    PRESSURE         393 

in  anotlicr  way,  bceauso  Henderson'  lias  shown  that  the  exposure  of 
the  heart  to  a  direct  pressure  of  this  kind  hinders  the  normal  filUnf^ 
power  of  this  organ  and  hence,  also  the  flow  through  the  lungs.  Cer- 
tain discrepancies  have  also  been  found  by  Erlanger  and  Fosterling, ^ 
as  well  as  by  Snyder,^  but  as  a  more  satisfactory  explanation  of  this 
phenomenon  has  not  been  submitted,  it  seems  best  to  adhere  to  the 
analysis  previously  given. 

The  Traube-Hering  curves  are  rhythmic  fluctuations  in  pressure, 
each  of  which  alwa3^s  enil)races  a  number  of  respiratory  variations."* 
They  are  long,  but  do  not  attain  a  significant  height.     Their  con- 


FiG.  206. — Traube-Hering  Curves. 

The  time  is  given  in  seconds.  The  smallest  pulsations  represent  the  cardiac  varia- 
tions, those  of  intermediate  size  the  respiratory  variations,  and  the  large  waves  the 
Traube-Hering  variations. 

spicuousness,  however,  may  be  increased  by  curarization,  anemia  of 
the  bulbar  centers  and  asphyxia.  They  are  commonly  ascribed  to 
irradiations  of  impulses  from  the  excited  respiratory  center  to  the 
vasomotor    center. 

Waves  of  similar  character  are  frequently  observed  in  normal 
animals  and  especially  in  those  narcotized  with  morphin.  They  are 
known  as  the  Mayer  curves  and  find  their  origin  in  a  hyperirritable 
condition  of  the  vasomotor  center.  This  hyperirritability  arises  in 
consequence  of  bulbar  anemia,  an  increased  venosity  of  the  blood, 
irritations  of  the  central  nervous  system  and  the  administration  of 
certain  drugs,  such  as  digitalis  and  strophanthus. 

^  Jour,  of  Physiol.,  xxxvii,  1908. 

2  Jour,  of  Exp.  Med.,  xv,  1912. 

'  Am.  Jour,  of  Physiol.,  xxxvi,  1915. 

*  Traube,  Zentralblatt  fiir  die  med.  Wissensch.,  iii,  1865,  882. 


394    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 


CHAPTER  XXXIII 
THE  BLOOD  FLOW 

The  Volume  of  the  Blood  Stream. — If  the  arterial  system  were  com- 
posed of  a  number  of  rigid  tubes,  each  ventricular  output  would  be 
forced  through  this  system  in  the  form  of  a  uniform  column  which 
would  come  to  a  standstill  at  some  distance  from  the  heart.  But  as  the 
vascular  system  is  elastic,  and  is  kept  in  a  state  of  hyperfilling  by  an 
appropriate  peripheral  resistance,  the  different  ventricular  discharges 
must  be  retained  temporarily  near  the  outlet  of  the  heart,  their 
retention  being  made  possible  by  an  enlargement  of  the  main  distribut- 
ing tube,  the  aorta.  The  elastic  recoil  immediately  following  this 
distention,  then  forces  a  portion  of  this  blood  into  the  more  peripheral 
segment  and  from  here  into  the  adjoining  one,  and  so  on  until  the  periph- 
ery has  been  reached.  In  this  way,  the  conditions  incited  by  the 
ventricular  discharge  are  repeated  again  and  again  and  are  thus 
propagated  throughout  the  arterial  system.  Moreover,  as  the  blood- 
bed  of  the  aorta  is  larger  than  that  of  its  branches  put  together, 
this  blood-vessel,  and  especially  its  ascending  and  transverse  portions, 
sei-ve  the  purpose  of  an  elastic  reservoir  from  which  all  the  peripheral 
blood-vessels  are  supplied. 

Soon  after  its  emergence  from  the  heart,  the  blood  enters  the  differ- 
ent branches  of  the  aortic  system  and  is  distributed  to  the  various 
tissues  and  organs  in  amounts  commensurate  with  their  activity.  In 
close  proximity  to  the  heart,  the  flow  veiy  nearly  equals  the  ventricular 
output,  only  that  amount  of  blood  having  been  removed  from  it  which 
is  destined  to  nourish  the  cardiac  musculature.  Farther  distally,  how- 
ever, the  reduction  becomes  more  apparent,  because  a  considerable 
quantity  of  blood  is  now  diverted  into  the  blood-vessels  of  the  head 
and  anterior  extremities.  In  endeavoring  to  obtain  an  idea  regarding . 
the  volume  of  the  blood  stream  in  any  particular  arteiy,  it  is  not 
sufficient  to  collect  the  blood  escaping  from  the  opened  blood-vessel  in 
a  graduated  cylinder,  because  the  removal  of  the  peripheral  resistance 
seriously  disturbs  normal  dynamical  conditions.  With  a  closed 
vascular  system,  two  procedures  are  practicable  which  may  be  desig- 
nated respectively  as  the  direct  and  the  indirect. 

The  direct  method  consists  in  connecting  the  artery  with  an  instrument  known 
as  a  current-measurer  or  stromuhr.  The  one  described  by  Ludwig^  is  composed 
of  two  glass  bulbs  {A  and  B)  which  are  placed  upon  a  metal  disc  (P)  and  may  be 
rotated  around  a  common  vertical  axis  (Fig.  207).     In  this  way,  it  is  possible  to 

1  Stolnikow,  Archiv  fur  Anat.  und  Phj^siol.,  1886.  This  instrument  has  been 
modified  by  Tigerstedt,  Skand.  Archiv  fiir  Physiol.,  iii,  1891. 


THE   BLOOD    FLOW 


395 


bring  the  bulbs  successively  into  communication  with  the  cannula  inserted  in 
the  central  end  of  the  artery  (C).  To  be^in  with,  one  of  the  bulbs  is  filled 
with  normal  saline  solution  and  the  other  with  oil.  The  latter  is  first  turned 
towanl  the  inilow  tube  {(').  On  permittint:;  the  l)lood  to  flow  into  this  instrument 
by  removinf:;  the  clip  temporarily  placed  upon  the  central  end  of  the  artery,  the 
oil  is  forced  upward  and  throuf^ii  the  con- 
necting tube  into  the  linil)  containing  the 
saline  solution.  When  the  latter  has  been 
completely  driven  into  the  peripheral  end 
of  the  artery,  the  Inilbs  are  quickly  re- 
versed so  that  the  oil  is  again  brought 
into  direct  communication  with  the  influx, 
while  the  blood  is  forced  into  distant  ar- 
terial channels.  In  order  to  obtain  the 
volume  of  the  blood  stream  it  is  necessary 
to  record  the  numlier  of  revolutions  of 
the  stromuhr  in  conjunction  with  the 
time.  Thus,  if  the  capacity  of  the  bulb 
is  5  c.c.  and  it  has  been  filled  12  times  in 
the  course  of  one  minute,  then  60  c.c.  of 
blood  have  passed  this  point  of  the  artery 
in  the  course  of  this  period. 

Much  more  serviceable  instruments 
for  the  calibration  of  the  blood  stream 
have  been  devised  by  Hlirthle^  and  Bur- 
ton-Opitz.^  Both  types  of  instruments 
contain  a  piston  which  moves  within  a 
cylinder  and  records  its  excursions  upon 
the  paper  of  a  kymograph.  For  this 
reason,  they  are  known  as  recording  stro- 
muhrs.  The  cylinder  of  the  instrument 
described  by  Burton-Opitz  is  adjusted 
horizontally  at  the  level  of  the  blood- 
vessel, while  the  resistance  of  the  piston  is 
minimized  by  counterpoising  (Fig.  208). 
By  means  of  a  double  U-shaped  valve 
with  which  the  central  and  peripheral 
segments  of  the  blood-vessel  are  con- 
nected, the  blood  may  be  diverted  either 
into  the  compartment  to  the  left  or  to 
the  right  of  the  piston.  The  piston  is 
thus  forced  to  move  successively  from 
left  to  right,  and  from  right  to  left,  its 
movements  being  recorded  upon  the  kymo- 
graph by  means  of  a  lever  and  connecting 
string.  This  instrument  having  been 
properly  calibrated,  the  quantity  of  blood 
which  has  traversed  it  may  be  read  off 
directly  from  the  paper.  Naturally,  the 
insertion  of  the  stromuhr  necessitates  a 
temporary  interruption  of  the  blood  flow 
in  this  vessel,  butunless  unduly  prolonged, 

normal  conditions  are  generally  reestablished  within  a  few  moments  after  the  re- 
moval of  the  clips.     As  the  instrument  is  filled  with  normal  saline  solution,  and  as 

1  Pfluger's  Archiv,  xcvii,  1903,  193. 

-  Ibid.,    cxxi,   1908,    150.     Ishikawa   and  Starling  have  described  a  current 
measurer  of  which  a  siphon  forms  the  essential  part. 


Fig.  207. — Ludwig's  Stromuhr. 
a.  Is  filled  with  oil  to  the  mark  (c.c), 
while  b  and  the  neck  are  filled  with  salt 
solution  or  defibrinated  blood;  p,  the 
movable  plate  by  means  of  which  the 
bulbs  may  be  turned  through  180  de- 
grees; cc,  for  the  cannulas  inserted  into 
the  artery;  s,  the  thumb  screw  for  turn- 
ing the  bulbs;  h,  the  holder.  When  in 
place  the  clamps  on  the  arteries  are  re- 
moved, blood  flows  through  c  into  a, 
driving  out  the  oil  and  forcing  the  salt 
solution  in  b  into  the  head  end  of  the 
artery  through  c'.  When  the  blood  en- 
tering a  reaches  the  mark,  the  bulbs  are 
turned  through  180  degrees  so  that  b  hes 
over  c.  The  blood  flows  into  b  and 
drives  the  oil  back  into  a.  When  it  just 
fills  this  bulb,  they  are  again  rotated 
through  ISOdegreos, andsoon.    (Howell.) 


396    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

the  blood  entering  it  is  always  returned  into  the  vascular  system  by  way  of  its 
distal  cannula,  the  volume  of  the  circulating  lilood  must  remain  the  same.  All 
in  all,  it  seems  fair  to  state  that  the  objections  which  may  l)e  raised  against  the 
use  of  this  instrument  (Starling)  are  in  no  way  more  valid  than  those  raised 
against  the  employment  of  manometers  or  physiological  apparatus  of  a  similar 
kind.i 


Fig.  208. — Diagram  of  Recording  Stromuhr. 
C,  cylinder;  K,  piston;  F,  piston-rod;  AR  and  AR,  tubes  for  influx  of  blood;  A> 
double  U-shaped  valve  connected  with  blood-vessel  at  B  and  B';  Di  and  D2,  positions 
occupied  by  valve  when  blood  is  directed  either  into  the  left  or  right  side  of  the  cylinder; 
Ro,  Sf,  H  and  St,  apparatus  required  for  registering  the  excursions  of  the  piston  upon 
the  paper  of  Xhe  kymograph. 


An  idea  regarding  the  volume  of  the  blood  flow  may  be  obtained  from  the 
accompanying  table  which  embraces  the  results  of  a  series  of  experiments  made 
by  Burton-Opitz^  and  Tschuewsky.'  The  values  here  given  are  calculated  for 
a  dog  weighing  about  15  kg. : 

1  An  optical  stromuhr  has  been  described  by  Hlirthle  in  Pfliiger's  Archiv, 
cxlvii,  1912,  509. 

2  Pfliiger's  Archiv,  cxxix,  1909,  189,  and  Quart.  Jour,  of  Exp.  Physiol.,  vii, 
1913,  57. 

'Ibid.,  xcvii,  1903,  214. 


THE    BLOOD    FLOW 


397 


Carotid  artery 

Femoral  artery 

Hepatic  artery 

Thyroid  artery 

Ext.  juRular  vein , 

Renal  vein 

Mesenteric  vein 

Splenic  vein 

Portal  vein 

Femoral  vein 

The  indirect  method  of  measuring  the  blood  flow  embraces  several  different 
procedures,  namely,  the  calorimetric,  plethysmof^raphic,  and  the  gas-analytical. 
The  calorimetric  method  devised  by  Stewart'  arrives  at  the  quantity  of  blood 
traversing  a  part,  by  measuring  the  amount  of  heat  liberated  by  it  in  a  certain 


c.c.  in  ft  sect 

)nd 

c.c.  in  a  minute 

2 .  -iA 

150 

0.87 

52 

2.39 

143 

0.37 

22 

2.40 

144 

1.64 

98 

2.74 

164 

0.95 

67 

4.56 

273 

0.85 

61 

Fig.  209. — Calorimetric    Method    of    Measuring    Blood-flow    in    Hands.     (From 
Stewart's  "A  Manual  of  Phytiiology,"  William  Wood  and  Co.,  Publishers.) 

period  of  time  and  by  ascertaining  the  difference  in  the  temperatures  between 
the  inflowing  and  outflowing  blood.  This  method  is  applicable  to  the  human  being. 
Having  established  the  basal  temperature  by  immersing  the  hands  or  feet  for  some 
time  in  water,  the  temperature  of  which  is  one  or  two  degrees  below  that  of  the 
arterial  blood,  they  are  rapidly  transferred  to  a  calorimeter  filled  with  water  of  the 
same  temperature.  As  the  parts  are  kept  motionless,  the  heat  given  off  by  them 
while  in  this  compartment,  must  be  derived  chiefly  from  the  blood  passing  through 
them.  The  temperature  of  the  arterial  blood  at  the  wrist  was  found  to  be  lower 
by  0.5°  C.  than  that  of  the  rectum,  while  the  venous  blood  exhibited  a  temperature 


1  Cleveland  Med.  Jour.,  x,  1911,  and  Heart,  iii,  1911. 


398    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

only  a  fraction  of  a  degree  above  that  of  the  water  in  which  the  parts  were  immersed. 
The  flow  is  calculated  in  grammes  per  minute  in  accordance  with  the  formula : 


Q  = 


H 


1 


M{T  -  T)  S 


Q  being  the  quantity  of  blood,  H  the  number  of  small  calories  given  off  in  M 
minutes,  T  the  temperature  of  the  entering  blood,  T'  the  temperature  of  the  out- 
flowing blood,  and  S  the  specific  heat  of  the  blood.     The  volume  of  the  hands  or 


Fig.  210. — Kidney  Oncometer. 
I,  the  kidney  is  placed  into  the  oncometer  consisting  of  two  hemispherical  parts, 
connected  with  a  recording  tambour  {T).     II,  the  sides  of  this  oncometer  are  lined  with 
rubber  membrane,  the  space  between  the  membrane  and  the  metal  wall  being  filled  with 
water  of  37°  C.     The  upper  bag  is  connected  with  a  recording  tambour. 

feet  is  measured  by  permitting  them  to  displace  an  equal  quantity  of  water  from  a 
graduated  receptacle.  The  bloodfiow  is  expressed  in  grammes  per  100  c.c.  of 
tissue  per  minute. 

These  tests  upon  the  hands  of  normal  individuals  have  given  the  average  value 
of  5.5  grammes  of  blood  per  100  c.c.  of  hand-volume  in  a  minute,  but  naturally, 
this  figure  is  subject  to  considerable  variations,  because  the  vascularity  of  a  part 
may  be  changed  at  any  time  either  by  influences  brought  to  bear  upon  it  directly,  or, 


Fig.  211. — Diagram  of  Schafer's  Air  Plethysmograph  (Splenic  Oncometer). 
P,  box  for  insertion  of  spleen;  R,  piston-recorder;  L,  writing  lever. 


in  an  indirect  way,  by  reactions  occurring  in  other  regions  of  the  body.  In  a  robust 
young  man  the  average  flow  amounted  to  12.8  grammes  per  100  c.c.  of  hand  per 
minute  for  the  right  hand  and  to  12. .3  grammes  for  the  left.  In  the  foot,  the 
flow  per  unit  of  volume  of  the  part  is  smaller  than  in  the  hand.  In  the  forearm  the 
flow  is  much  less  than  in  the  hand  (Hewlett). 

The  blood  supply  of  an  organ  may  also  be  determined  in  an  approximate  way 


THE    BLOOD    FLOW 


399 


by  the  plethysmngraphic  method.^  The  part  to  be  experimentod  upon  is  enclosed 
in  a  rigid  capsule,  known  as  a  plethysmoKraph,  which  is  then  connected  with  a 
volume  recorder  or  an  ordinary  taniljour.  The  shape  of  this  instrument,  however, 
must  necessarily  be  changed  to  suit 
the  anatomical  peculiarities  of  the 
organ.  We  have  so  far  been  placed  in 
possession  of  plethysmographs  for  the 
kidney,  spleen,  heart,  lung,  liver,  brain 
and  the  anterior  and  posterior  extremi- 
ties. Special  names  have  been  given 
to  these;  the  one  for  the  heart  being 
designated  as  a  cardiometer,  and  the 
one  for  the  kidney  as  a  kidney 
oncometer,  in  contradistinction,  for 
example,  to  the  splenic  and  hepatic 
oncometers. 

The  principle  of  plethysmography 
may  be  illustrated  with  the  help  of  the 

cranial  cavity.  If  the  .skull  is  trephined,  and  the  trephine-opening  connected  with 
a  recording  drum,  the  variations  in  the  volume  of  the  brain  coincident  with  the 
various  bodily  activities,  may  be  accurately  followed  upon  the  paper  of  a  kymo- 
graph.^    This  same  procedure  may  be  practised  upon  any  other  organ  provided,  of 


Fig.  212. — Brodie's  Recorder, 
A,  rubber  pouch;  R,  is  placed  between 
two  plates  A  and  B;  the  latter  is  equipped 
with  a  writing  lever. 


Fig.  213. — A  Schematic  Diagram  of  Mosso's  Plethysmograph  for  the  Arms 
a,  The  glass  cylinder  for  the  arm,  with  rubber  sleeve  and  two  openings  for  filling 
with  warm  water;  s,  the  spiral  spring  supporting  the  test  tube,  t.  The  spring  is  so  cali- 
brated that  the  level  of  the  liquid  in  the  test  tube  above  the  arm  lemains  unchanged  as 
the  tube  is  filled  or  emptied.  The  movements  of  the  tube  are  recorded  on  a  drum  by 
the  writing  point,  p.     {Howell.) 


course,  that  its  shape  and  position  permit  of  its  being  enveloped  by  a  rigid  capsule. 
Air  transmission  or  fluid  transmission  may  be  employed,  and  the  organ  may  be 

^  For  a  full  description,  see :  Frangois- Frank,  in  Marey's  Traveaux  du  Labora- 
toire,  1876. 

*  Suggested  by  Hallion  and  Comte,  Arch,  de  Phys.  norm,  et  pathol.,  1894. 


400    THE    MECHANICS    OF   THE    CIRCULATION,    HEMODYNAMICS 

exposed  to  the  medium  directly,  as  in  Mosso's  instrument, ^  or  may  first  be 
surrounded  by  an  envelope  of  soft  rubber  (Fig.  210).  The  changes  in  volume  which 
the  organ  undergoes  may  be  recorded  by  means  of  an  ordinary  U-shaped  manom- 
eter filled  with  water,  or  with  the  help  of  tambours  of  the  type  designed  by  Marey 
and  Hiirthle,  and  the  piston-recorders  constructed  in  accordance  with  the  suggestions 
of  Roy,^  Ellis, ^  SchJifer,^  Hiirthle,^  and  Lombard.*  A  very  convenient  and  prac- 
tical recorder  has  been  described  by  Brodie,'  the  essential  constituent  of  which  is 
a  pair  of  bellows  made  of  thinnest  rubber  and  equipped  with  a  delicate  writing 
lever.  A  plethysmograph,  which  is  frequently  made  use  of  in  the  laboratory,  is  the 
one  designed  for  the  reception  of  the  hand  and  forearm  (Figs.  213and214).  Itcon- 
sists  of  a  cylindrical  chamber  of  glass  which  is  filled  with  warm  water  through  two 
openings  in  its  upper  wall.     The  space  around  the  arm  is  made  air-tight  by  a  cuff  of 


Fig.  214. — Detailed  Drawing  of  the  Glass  Plethysmograph  with  Rubber  Glove  to 
Prevent  Escape  of  Water. 
2,  The  glove  with  its  gauntlet  reflected  over  the  end  of  the  glass  cylinder;  1  and  3, 
supporting  pieces  of  stout  rubber  tubing;  D  and  E,  sections  ol  outer  and  inner  rings  of 
hard  rubber  to  fasten  the  reflected  rubber  tubing  and  reduce  the  opening  for  the  arm. 
{Hoicell.) 


rubber  membrane  which  is  adjusted  in  such  a  way  that  it  does  not  compress  the 
blood-vessels  of  this  locality.  The  small  orifice  in  the  far  end  of  this  cylinder  is 
connected  with  the  recording  instrument.  This  arrangement  allows  any  change 
in  the  volume  of  the  arm  to  cause  a  corresponding  displacement  of  the  water  which 
in  turn  varies  the  level  of  the  recording  lever. 

The  uses  to  which  this  instrument  may  be  put  are  very  manifold.  It  has  been 
stated  above  that  the  cardiometer  may  be  employed  to  determine  the  volume 
of  the  output  of  the  heart  by  obtaining  the  differences  in  the  volume-curve  of  this 
organ  during  systole  and  diastole.  In  a  similar  way  the  attempt  has  been  made  by 
Brodie  to  measure  the  blood  supply  of  the  kidney  by  temporarily  blocking  its 
venous  return  and  recording  the  increase  in  volume  occurring  at  this  time.     The 

^  Diagnostik  des  Pulses,  Leipzig,  1879. 

2  Jour,  of  Physiol.,  iii,  1880,  203. 

3  Ibid.,  vii,  1886,  309. 
^  Ibid.,  XX,  1896,  1. 

6  Pfluger's  Archiv,  liii,  1893. 
«  Am.  Jour,  of  Physiol.,  iii,  1890. 

^  Jour,  of  Physiol.,  xxvii,  1902.  A  very  simple  method  of  registration  has  been 
described  by  O.  Miiller  (Archiv  fiir  Anat.  und  Physiol.,  1904,  Suppl.). 


THE    BLOOD    FLOW 


401 


supposition  in  dotorminations  of  this  kind  is  that  the  venous  drainaKe  l)ahinces  the 
arterial  iiifhix  and  that  an  increase  or  decrease  in  the  vohnne  of  an  orRan  may  he 
taken  as  a  measure  of  its  vascularity.  This  inference  may  he  a  safe  one  to  make 
when  (hvilins  with  passive  and  compact  organs,  hut  may  lead  to  errors  if  the  part 
experimented  upon  is  soft  in  texture  and  emhraces  varying  amounts  of  active 
tissue  elements.  The  plethysnu)Kraph  has  also  l)een  employed  for  the  registration 
of  those  chauKes  in  the  volume  of  i)arts  which  occur  in  conse(iuence  of  the  activity 
of  the  heart  or  respiration,  and  also  in  consetjuence  of  different  experimental 
procedures.  In  all  these  cases  it  is  assumed  that  the  alterations  in  the  volume 
of  a  part  arc  dependent  upon  displacements  of  fluid  and  are  therefore  directly 
attributable  to  changes  in  its  blood  supply.  When  a  study  is  made  of  the  volume- 
curve  of  the  arm  it  will  be  seen  to  be  made  up  of  smaller  and  larger  oscillations, 
the  first  of  which  occur  synchronously  with  the  action  of  the  heart,  and  the  second, 
with  the  respiratory  motions.  This  means  that  the  systolic  discharge  of  the  heart 
increases  the  vascularity  of  this  part  momentarily  and  that  a  similar  increase 
takes   place   throughout  inspiration.     A  most  striking   demonstration   of  these 


Fig.  215. — Plethysmographic  Curve  of  Foreahm. 

Showing  the  cardiac  and  respiratory  variations  in  the  volume  of  the  arm.     The 

derided  decrease  in  its  volume  oKserved  here  is  due  to  mental  activity;  hence,  to  a. 

transfer  of  blood  from  the  cutaneous  circuits  into  that  of  the  cerebrum.  (Howell.) 


changes  may  be  had  by  observing  the  surface  of  the  brain  through  a  rather  small 
trephine  opening  which  contains  a  small  quantity  of  warmed  saline  solution. 
The  level  of  the  solution  will  be  seen  to  rise  with  every  systole  and  to  fluctuate  in 
larger  waves  with  every  respiration. 

When  taken  with  a  fairly  sensitive  apparatus,  the  general  appearance  of  the 
volume-curve  of  a  part  presents  practically  the  same  details  as  a  tracing  of  the 
blood  pressure.  It  displays  not  only  the  cardiac  and  respiratory  oscillations,  but 
also  Traube-Hering  waves  and  all  those  variations  which  are  dependent  upon  more 
lasting  increases  or  decreases  in  the  blood  supply.  In  this  way,  for  example,  it  has 
been  demonstrated  by  Mosso  that  the  vascularity  of  the  brain  is  diminished  during 
sleep,  because  the  intracranial  blood  is  transferred  during  this  period  into  other 
circuits  of  the  bod^^ 

The  chemical  method  which  has  been  introduced  by  Bornstein^  is  founded  upon 
the  principle  that  the  volume  of  Idood  passing  through  the  lungs  of  a  man  may 
be  obtained  by  calculation  from  the  quantity  of  nitrogen  absorbed  by  the  blood. 
This  value  is  derived  from  the  tension  difference  of  this  gas  in  the  alveolar  air  and 
the  blood.     Zuntz  and  his  co-workers,-  as  well  as  Krogh  and  Lindhard,^  employed 

1  Pfliiger's  Archiv,  xxxii,  1900. 
^  Zeitschr.  fiir  Balneologie,  iv,  1912. 
3  Skand.  Archiv  fur  Physiol.,  xxvii,  1912,  100. 
26 


402    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 


nitrous  oxid  instead  of  nitrogen.  A  similar  procedure  has  been  followed  by  Boothby  ^ 
who  has  determined  the  minute-volume  of  the  pulmonary  blood  stream  of  man  dur- 
ing rest  and  muscular  exercise.  These  experiments  have  shown  that  the  total  blood 
flow  through  the  lungs  amounts  to  more  than  3  liters  in  a  minute,  and  hence,  about 
60  c.c.  of  lilood  must  be  discharged  by  each  systole  of  the  heart.  But  this  figure 
may  be  varied  somewhat  by  changes  in  posture,  muscular  work,  and  a  more  thor- 
ough ventilation  of  the  lungs  and  consumption  of  oxygen. 

The  Velocity  of  the  Blood  Flow. — -We  have  seen  that  the  main  pur- 
pose of  the  circulation  is  to  supply  the  different  colonies  of  cells  with 
nutritive  material  and  to  remove  from  them  all  those  substances  which 
are  of  no  further  use  to  them.  This  interchange  occurs  in  the  capil- 
laries, where  the  blood  and  the  body-fluid  are  separated  from  one 
another  by  only  a  very  thin  layer  of  cells.  These  tubules,  therefore, 
are  of  much  greater  metabolic  value  than  the  arteries  and  veins.  The 
latter  merely  play  the  part  of  supply  channels. 

The  systemic  and  pulmonary  circuits  arise  from  single  tubes,  the 
repeated  division  and  subdivision  of  which  eventually  gives  rise  to  an 

intricate  network  of  the  finest  pos- 
sible tubules,  the  capillaries  (Fig. 
216).  The  gradual  reunion  of 
these  in  turn  leads  to  the  forma- 
tion of  large  collecting  channels 
which  are  finally  united  in  a  com- 
mon reservoir,  the  auricles.  It 
should  be  remembered,  however, 
that  the  total  cross-  section  of  the 
vascular  system  increases  con- 
stantly in  the  direction  of  the  capil- 
laries, but  diminishes  again  distally 
to  these,  and  the  more  so  the  closer 
we  approach  the  heart.  The 
smallest  blood-beds,  therefore,  are 
found  at  the  aorta  and  at  the  vense 
cavsB.  The  latter,  however,  is  somewhat  larger  than  the  former. 
Their  peripheral  ramifications  put  together  represent  a  blood-bed 
which  is  very  much  larger  than  that  of  either  the  arteries  or  veins. 
As  has  just  been  stated,  the  blood-bed  again  decreases  in  size  on  the 
other  side  of  the  capillaries,  because  while  the  sectional  areas  of  the 
different  single  veins  increase  constantly  as  they  unite  into  larger 
channels,  their  combined  area  becomes  less.  Consequently,  the  size' 
of  the  vascular  system  at  the  venae  cavse  is  almost  as  small  as  that  at 
the  aorta.  It  is  also  of  interest  to  note  that  the  blood-bed  of  the 
aorta  is  somewhat  larger  than  that  of  all  the  arteries  combined,  which 
fact  again  tends  to  show  that  the  aorta  serves  as  the  elastic  reser- 
voir of  the  circulatory  system. 

As  far  as  the  velocity  of  the  blood  flow  is  concerned,  the  preceding 
statements  must  show  immediately  that  the  speed  of  flow  is  greatest 
1  Am.  Jour,  of  Physiol.,  xxxvii,  1915,  383. 


Fig.    216. — Diagram   to    Illustrate 
THE   Changes   in  the   Cross-section  of 
THE  Vascular  System. 
A,  aorta;   Ar,  arteries;  C,  capillaries;  T', 
veins;  VC,  vena  cava. 


THE   BLOOD    FLOW  403 

in  the  arteries,  least  in  the  capillaries,  and  intermediate  in  the  veins. 
(Fig.  217).  These  clianges  in  the  flow,  as  we  shall  see  later,  are  in  no 
way  different  from  those  displayed  by  water  while  traversing  a  tube 
of  varying  diameter.  Provided,  therefore,  that  the  quantity  of  the 
circulating  blood  remains  the  same,  its  speed  of  flow  must  be  inversely 
proportional  to  the  size  of  the  blood-bed.  It  has  been  stated  that  the 
cross-area  of  the  capillaries  is  from  600  to  800  times  larger  than  that 
of  the  aorta.  Thus,  Tigerstedt  estimates  the  capillary  expanse  of 
man  at  800  to  2200  sq.  cm.,  while  Nikolai,  upon  the  basis  of  a  ventricu- 
lar output  of  75  c.c,  gives  the  value  of  1500  sq.  cm.  It  need  not 
surprise  us,  therefore,  to  find  that  a  most  profound  reduction  in  the 
speed  of  the  blood  flow  results  as  soon  as  the  capillaries  have  been 
reached. 

In  the  second  place,  the  velocity  of  the  flow  in  any  tube  is  dependent 
upon  the  friction  to  which  the  constituents  of  the  fluid  are  exposed. 

S  -— . 


V 

r.  /  ^ 

f  \ 
/ 
/ 


B^. 


y 


• 


Fig.  217. — Diagram    to    Illustrate   the    Relationship    Between   the    Size   of   the 
Blood-bed  and  the  Velocity  of  the  Flow. 
B,  cross-section;  S,  speed  of  flow  in  {A)  arteries;  C,  capillaries  and  (F)  veins;  Z, 
zero  line. 

Thus,  we  recognize  two  types  of  friction,  namely  the  one  produced  by 
the  fluid  in  coming  in  contact  with  the  wall  of  the  tube  and  the  one 
produced  by  its  molecular  constituents  when  thrown  against  one 
another.  The  former  is  called  ''external"  friction  and  the  latter  "in- 
ternal" friction  or  viscosity.  For  this  reason,  the  blood  does  not  speed 
onward  as  a  uniform  column,  but  is  separated  into  layers,  the  outer- 
most of  which  remains  stationary,  while  the  central  one,  forming  the 
core  of  the  stream,  moves  ahead  with  the  greatest  possible  speed.  The 
red  corpuscles  and  "heavier  elements  are  thus  forced  into  the  central 
stream,  while  the  lateral  zone  is  filled  chiefly  with  plasma.  Hence,  in 
attempting  to  determine  the  speed  of  the  blood  flow  under  the  micro- 
scope, we  really  measure  the  rate  of  progression  of  the  cellular  elements 
in  the  axial  stream.  If  these  could  be  removed,  the  speed  of  the 
plasma-blood  would  thereby  be  much  augmented.  Obviously,  there- 
fore, the  solids  tend  to  retard  the  flow,  because  they  heighten  the  in- 
ternal and  external  frictions. 

If  these  two  factors  are  now  united  under  the  general  term  of 
peripheral  resistance,  the  further  conclusion  may  be  drawn  that,  every- 


404    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

thing  else  remaining  equal,  the  speed  of  flow  must  be  least  in  that  di- 
vision of  the  circulatory  system  in  which  the  greatest  resistance  is 
encountered.  It  has  previously  been  shown  that  the  friction  is  greatest 
in  the  capillaries,  and  hence,  it  may  be  gathered  that  those  tubules 
place  the  greatest  resistance  in  the  path  of  the  circulating  blood. 
A  few  figures  may  suffice  to  illustrate  this  point.  Some  of  the  capil- 
laries are  so  small  that  the  red  cells  cannot  enter  them  at  all,  while 
those  which  possess  a  diameter  of  5-7 ju,  permit  their  passage  only  after 
they  have  been  compressed  into  a  shape  approaching  the  elliptical. 
The  larger  capillaries,  measuring  14ju  and  over  in  diameter,  allow  several 
erythrocytes  to  pass  side  by  side.  The  average  length  of  these  tubules 
has  been  estimated  by  Tigerstedt  at  0.02  cm.  Moreover,  if  the 
average  cross-section  of  a  capillary  is  7.5/u-,  a  capillary  area  of  1500 
sq.  cm.  would  embrace  two  billion  capillaries,  placed  side  by  side. 
Ordinarily,  of  course,  the  capillaries  recur  at  distances  of  less  than 
0.02  cm. 

In  the  arterial  channels,  on  the  other  hand,  the  blood  encounters 
only  a  relatively  slight  resistance,  so  that  it  is  able  to  retain  practically 
the  entire  pressure  developed  by  the  heart  until  it  arrives  in  the  arteri- 
oles. The  blood  rushes  through  these  vessels  with  a  considerable 
speed,  but  its  function  is  in  no  way  curtailed  thereby,  because  a  direct 
interchange  between  it  and  the  neighboring  cells  does  not  take  place 
until  the  capillaries  proper  have  been  reached.  Here  radically  different 
conditions  are  met  with.  Since  the  walls  of  these  tubules  consist  of  a 
single  layer  of  elongated  and  flattened  cells  which  are  only  slightly 
thickened  in  the  regions  of  the  nuclei,  the  tissues  are  brought  into  al- 
most immediate  relationship  with  the  blood.  The  latter,  moreover, 
moves  past  these  cells  with  the  slowest  possible  speed.  This  is  im- 
portant, because  it  is  essential  that  a  sufficient  time  be  allowed  for  the 
interchange  of  material  between  the  blood  and  the  lymph  bathing  the 
tissue-cells.  In  the  veins,  practically  the  same  conditions  prevail  as 
in  the  arteries.  The  nutritive  interchanges  having  been  completed 
in  the  capillaries,  the  blood  again  rushes  onward  at  a  much  greater 
speed,  without,  however,  at  all  equaling  that  of  the  arterial  stream. 

The  Determination  of  the  Velocity  of  the  Blood  flow. — As  the 
dynamical  conditions  in  the  different  segments  of  the  vascular  system 
differ  considerably,  it  is  quite  impossible  to  employ  the  same  method  in 
all  cases.  Volkmann  (1850)  has  succeeded  in  obtaining  approximate 
values  for  the  speed  of  the  arterial  flow  in  the  following  way:  A  U- 
shaped  glass  tube  of  definite  length  and  caliber  is  connected  with  the 
artery  in  such  a  way  that  the  blood  may  be  made  to  pass  either  through 
it  or  through  a  much  shorter  tube  situated  in  the  base  of  this  instru- 
ment (Fig.  218).  To  begin  with,  the  tubes  of  this  instrument  which  is 
known  as  a  hemodromometer ,  are  filled  with  normal  saline  solution  which 
is  then  forced  into  the  circulation  by  the  entering  blood.  The  length 
of  the  U-tube  being  known,  the  speed  of  flow  may  be  determined  with- 


THE    BLOOD    FLOW 


405 


out  difficulty  by  simply  noting  the  time  when  the  ])loo(l  enters  and 
leaves  its  orifices. 

Instruments  embodying  the  principle  of  Pilot's  tubes  have  been 
designed  by  Cybulski.'  Two  tubes  (d  and  d')  which  have  been  bent 
at  right  angles,  are  inserted  in  the  blood-vessel  in  such  a  way  that  the 
orifice  of  one  points  in  the  direction  of  the  blood  stream  and  that  of 
the  other  against  it  (Fig.  219).  The  level  of  the  saline  solution  with 
which  they  have  previously  been  filled  will  then  rise  in  the  latter  and 


<-c:?;::i 


*Z^' 


Fig.  218.  Fig.  219. 

Fig.  218. — Volkmann's  Hemodromometer. 

A  and  B,  cannulas  for  connecting  the  central  and  distal  ends  of  the  blood-vessel  with 
this  instrument.     C,  short  cut  through  base  of  instrument;  £>,  U-shaped  tube  of  definite 
length.     The  blood  may  be  diverted  into  the  latter  at  any  moment  by  turning  the  valves 
E  and  F. 
Fig.  219. — Diagram  to  Show  the  Principle  of  the  Ctbulski  Photo-hemotacho- 

METER. 


fall  in  the  former.  The  push  (d)  and  the  pull  (d')  which  the  moving 
blood  exerts  upon  them  must,  of  course,  be  directly  proportional  to 
the  speed  of  the  flow.  It  need  scarcely  be  mentioned  that  these  varia- 
tions in  the  levels  of  the  liquid  (h  and  h')  may  be  recorded  either  by 
means  of  ordinary  tambours  connected  with  the  ends  of  these  tubes, 
or  by  means  of  a  beam  of  reflected  light. 

The  hemotachometer,  devised  by  Chauveau  and  Lortet,^  is  another 
instrument  of  this  type.  It  consists  of  a  T-tube  made  of  metal,  in 
which  a  very  delicate  pendulum  is  suspended  (Fig.  220).  The  short 
arm  of  the  latter  projects  into  the  blood  stream,  while  its  long  arm 

iPfliiger's  Archiv,  xxxvii,  1885,  382. 
2  Jour,  de  la  Physiol.,  iii,  1860,  695. 


406    THE    MECHANICS    OF   THE    CIRCULATION,    HEMODYNAMICS 


rests  upon  a  millimeter  scale.  As  the  blood  strikes  its  lower  end,  it  is 
deflected  in  the  direction  of  the  current,  its  degree  of  deflection  being 
clearly  marked  upon  the  scale.  Naturally,  this  apparatus  is  first 
graduated  with  currents  of  water  of  known  velocity.  It  can  also  be 
made  to  register  its  deflection  by  simply  attaching  the  long  arm  of  the 
pendulum  to  the  membrane  of  a  tambour. 

The  speed  of  the  flow  in  the  arteries  and  veins  may  also  be  de- 
termined with  the  help  of  the  stromuhr  which,  as  has  been  stated  above, 
measures  the  quantity  of  blood  traversing  a 
blood-vessel  in  a  given  period  of  time.  This 
calculation,  however,  also  necessitates  the  de- 
termination of  the  internal  diameter  of  this 
vessel.  Burton-Opitz^  and  Tschuewsky^  have 
made  use  of  the  following  simple  procedure 
in  obtaining  this  value.  Having  ascertained 
the  external  diameter  by  means  of  calipers, 
the  blood-vessel  was  gently  compressed  be- 
tween two  thin  platelets  of  glass  until  it  be- 
came empty.  The  thickness  of  the  platelets 
and  vessel  wall  was  then  subtracted  from 
the  external  diameter,  and  in  addition  also 
the  thickness  of  the  platelets.  The  fact  that 
the  speed  in  the  arteries  is  astonishingly 
great  has  been  brought  out  by  the  experi- 
ments of  Volkmann,  Dogiel  and  Chauveau. 
The  maximal  speed  in  the  carotid  artery  of  the 
dog  is  given  as  500  mm.  in  a  second  during 
systole  and  as  250  mm.  during  diastole.  In 
the  horse,  the  speed  varies  between  520  mm. 
and  150  mm.  in  a  second,  and  naturally,  these 
systolic-diastolic  differences  are  most  evident 
in  the  arteries  in  the  immediate  vicinity  of 
the  heart.  In  the  smaller  arteries  the  flow  is 
quite  constant.  The  same  holds  true  of  the 
capillary  flow  although  it  may  be  rendered 
remittent  at  any  time  by  producing  a  slight  obstruction  centrally  to 
the  capillary  area.  Burton-Opitz  and  Tschuewsky  have  furnished 
the  following  average  values: 

Carotid  artery 241 . 0  mm.  in  a  second 

Femoral  artery 234 . 4  mm.  in  a  second 

Hepatic  artery 350. 0  mm.  in  a  second 

In  general,  therefore,  it  may  be  said  that  the  velocity  of  the  blood 
flow  in  the  peripheral  arteries  amounts  to  250-300  mm.  in  a  second. 
It  decreases  somewhat  in  the  smaller  arteries,  reaching  its  minimum 

1  Am.  Jour,  of  Physiol,  vii,  1902,  435. 

2  Pfluger's  Archiv,  xcvii,  1903,  286. 


Fig.  220.— The  Hemo- 

DROMOGRAPH     OF     ChAUVEAU 
AND    LORTET. 

B,  blood-vessel.  The 
end  of  the  pendulum  (P) 
is  played  against  by  the 
blood,  its  deflection  being 
registered  by  the  receiving 
drum  (7")  which  in  turn  is 
connected  with  a  recording 
tambour  (K).  The  pendu- 
lum is  contained  in  a  cannula 
(M). 


THE    BLOOD    FLOW  407 

value  at  the  arteriocapillarv  junction.  On  the  venous  side,  such 
liigh  values  are  not  encountered  under  ordinary  conditions.  Thus,  if 
the  accompanying  determinations  of  Burton-Opitz'  are  used  as  a 
guide,  it  must  be  concluded  that  the  speed  of  the  venous  blood  is  only 
about  one-fourth  as  great  as  that  of  the  arterial,  viz. : 

Ext.  jugular  vein 80. 0  mm.  in  a  .second 

Renal  vein 63 . 0  mm.  in  a  second 

Mesenteric  vein 83 . 6  mm.  in  a  second 

Femoral  vein 61.6  mm.  in  a  second 

It  is  slowest  in  the  vicinity  of  the  capillaries  and  fastest  in  the  central 
veins;  moreover,  when  the  blood  reaches  the  neighborhood  of  the 
heart,  it  is  brought  under  the  influence  of  the  right  auricle  and  shows 
alterations  in  flow  similar  to  those  encountered  in  the  central  arterial 
trunks.  Thus,  it  has  been  proved  by  Burton-Opitz-  that  the  influx 
into  the  right  auricle  is  not  constant,  but  is  diminished  during  the 
periods  of  high  intra-auricular  pressure,  i.e.,  during  the  systole 
of  the  auricles  and  again  during  the  systole  of  the  ventricles.  It 
may  be  surmised  that  the  heart  influences  the  current  in  the  pulmonary 
veins  in  a  very  similar  manner. 

The  capillaries,  of  course,  are  not  accessible  to  any  one  of  the 
instniments  described  previously.  In  the  frog,  however,  fairly 
accurate  results  may  be  obtained  by  placing  a  translucent  capillary 
area,  such  as  the  web  or  mesentery^  under  the  microscope  in  such  a 
way  that  a  rather  straight  capillary  comes  to  he  directly  across  the 
divisions  of  an  ocular  micrometer.  The  time  is  then  determined 
w^hen  a  certain  erythrocyte  enters  and  leaves  this  capillary.  The 
length  of  this  tubule  is  ascertained  later  on  by  determining  the  mag- 
nification, which  requires  a  comparison  of  the  ocular  micrometer  with 
the  stage  micrometer.  By  this  procedure  Weber'  and  Volkmann* 
have  found  the  velocity  of  the  capillary  blood  stream  to  be  0.5  to  0.8 
mm.  in  a  second. 

Vierordt^  has  also  described  a  method  which  is  appHcable  to  man 
and  depends  upon  the  following  entoptic  observation.  As  the  red 
cells  traverse  the  retinal  blood-vessels  they  cast  their  shadows  upon 
the  underlying  rods  and  cones.  The  visual  sensations  set  up  by  the 
latter  may  be  rendered  clearly  perceptible  in  an  indirect  manner  by 
fixedly  gazing  at  a  white  surface  placed  at  a  distance  of  11-16  cm. 
in  front  of  the  eyes.  Having  first  determined  the  speed  of  the  pro- 
jected shadows  upon  the  screen,  the  speed  of  the  red  cells  in  the  retinal 
vessels  may  be  ascertained  in  accordance  with  the  proportion: 

,  6c 

a  -.o  =  c:x-,x  =  — 

a 

1  Pfluger's  Archiv,  c.xxiv,  1908,  469. 

2  Am.  Jour,  of  Phvsiol.,  vii,  1902,  435. 

3  .\rchiv  fiir  Anat.  und  Physiol.,  1838,  450. 

*  Haemodynamik,  1850. 

*  Archiv  fiir  physiol.  Heilkunde,  xv,  1856. 


408    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

in  which  a  stands  for  the  distance  between  the  screen  and  the  anterior 
nodal  point,  h  for  the  distance  between  the  retina  and  the  posterior 
nodal  point,  and  c  for  the  distance  traversed  by  the  projected  image. 
Values  between  0.6  and  0.9  mm.  in  a  second  have  been  found  by  this 
method.  If  it  is  now  remembered  that  the  length  of  the  true  capil- 
laries varies  between  0.4  and  0.7  mm.,  the  general  conclusion  may  be 
drawn  that  a  red  cell  traverses  a  capillary  of  average  length  in  about 
1  second. 

The  Circulation  Observed  under  the  Microscope. — The  study  of 
the  blood  flow  was  made  possible  at  an  early  date  by  the  discovery  of 
the  microscope.  To  begin  with,  cold-blooded  animals  were  employed, 
partly  because  their  tissues  are  more  accessible  and  resistant,  and 
partly  because  their  erythrocj^tes  are  much  larger  than  those  found 
in  warm-blooded  animals.  These  observations  may  be  arranged  in  the 
following  chronological  order : 

Malpighi  (168G):  Lung,  mesentery,  urinary  bladder  of  the  frog. 
Leeuwenhoek  (1689):  Tail  of  the  tadpole  and  fish,  wing  of  the  bat. 
Cowper  (1704):  Mesentery  of  the  rabbit. 
Spallanzani  (1773):  Embryo  of  the  chick. 
Hueter  (1879) :  Mucous  membrane  of  man. 
Ewald  (1896):  Lung  of  the  triton. 

When  a  capillary  area  is  subjected  to  a  magnification  of  about  15 
diameters,  it  will  be  seen  that  many  of  its  tubules  are  extremely 
small  and  do  not  permit  the  passage  of  an3'thing  more  than  the  plasma 
and  occasional  white  cells.  Others,  again,  possess  a  somewhat  larger 
caliber  and  allow  two  or  three  red  cells  placed  side  by  side  to  traverse 
them.  The  most  interesting  picture,  however,  is  presented  in  those 
tubules  which  are  just  sufficiently  large  to  permit  the  entrance  of 
single  erythrocytes,  so  that  it  becomes  possible  to  follow  them  as  they 
wend  their  way  in  single  file  thi'ough  these  cu'cuitous  passages.  In 
fact,  in  many  cases  these  elements  must  be  considerablj^  elongated 
before  they  can  enter  these  tubules.  They  may  be  thrown  across  a 
bifurcation  and  be  rocked  back  and  forth  for  some  moments  before  they 
manage  to  escape  into  one  or  the  other  of  these  branches.  The  latter 
phenomenon,  in  particular,  permits  us  to  obtain  a  clear  idea  regarding 
the  elastic  properties  of  these  elements,  as  well  as  regarding  the  friction 
and  resistance  which  they  must  overcome  in  theii-  journey  through 
these  tubules. 

In  general,  it  may  be  said  that  the  principal  characteristics  of  the 
capillary  flow  are  its  slowness  and  constancy.  The  arterial  capillaries 
and  arterioles  are  much  larger  than  the  capillaries  proper  and  are, 
therefore,  able  to  accommodate  a  much  greater  number  of  red  cells. 
Furthermore,  as  the  speed  of  flow  within  them  is  much  greater,  it  is 
difficult  to  distinguish  the  individual  cells.  The  venous  capillaries 
and  venules  show  essentially  the  same  characteristics,  but  as  the  flow 
within  them  is  not  so  rapid,  the  different  red  cells  may  be  more  easily 
differentiated  from  one  another.     On  the  arterial  side,  the  stream 


THE    BLOOD    FLOW  409 

presents  a  clear  outer  zone,  measuring  about  0.01  mm.  in  width  and 
containing  onlj'  plasma  and  a  few  leukocytcis,  as  well  as  a  dark  central 
zone  in  which  the  red  cells  are  massed.  The  platelets  occupy  the 
peripheral  layers  of  the  stream.  This  arrangement  is  also  evident 
in  the  venules,  but  as  the  venous  current  is  less  rapid,  the  red  cells 
are  more  widely  scattered  and  the  mai'ginal  zone  is  not  so  clearly 
defined.  In  the  capillaries,  very  naturally,  the  distribu^^ion  of  the 
corpuscular  elements  cannot  be  dominated  so  much  by  ordinary 
physical  conditions,  because  these  channels  are  so  small  that  one  or 
two  erythrocytes  placed  side  by  side  fill  them  completely.  Another 
means  of  differentiating  between  the  true  capillaries  and  their  supply 
and  collecting  tubules  is  presented  by  the  color  of  the  blood.  It  is 
darkest  in  the  venules  owing  to  the  presence  of  greater  amounts  of  car- 
bon dioxid,  and  lightest  in  the  capillaries,  because  the  red  cells  are  here 
spread  out  in  thin  layers  and  single  cells,  as  has  been  mentioned  above, 
are  practically  colorless.  Still  another  means  of  differentiation  is 
furnished  by  the  structural  appearance  of  the  difTerent  blood-vessels. 
As  the  wall  of  a  true  capillary  is  composed  of  only  a  single  row  of 
flattened  cells,  it  cannot  be  made  out  veiy  clearly.  Neither  is  it 
possible  to  focus  a  venule  very  sharply.  The  arterial  capillaries,  on 
the  other  hand,  are  generally  well  defined.  This  is  especially  true  of 
the  arterioles,  owing  to  the  deposition  of  smooth  muscle  cells  within 
their  wall.  Moreover,  these  tubules  generally  pursue  a  serpentine 
course,  whereas  the  venous  tubules  are  rather  straight. 

The  Circulation  Time. — A  droplet  of  blood  leaving  the  left  ven- 
tricle may  pursue  many  different  courses.  It  may  enter  the  coro- 
nary circuit  and  return  to  its  starting  point  within  a  very  short  time, 
or  it  may  pass  through  the  portal  organs,  the  posterior  extremity,  the 
brain  and  other  parts,  in .  which  cases  a  very  much  longer  period  of 
time  will  be  required  before  it  can  again  reach  the  cardiac  vestibule. 
E.  Hering^  attempted  to  determine  the  time  required  to  complete  the 
circuit  of  the  vascular  system  by  introducing  a  chemical  substance 
into  the  blood  which  could  be  easily  recognized.  He  made  use  of 
solutions  of  potassium  ferrocyanid  which  were  injected  into  the  right 
external  jugular  vein  and  were  tested  for  in  the  blood  withdrawn 
from  the  corresponding  vein  on  the  opposite  side.  These  samples  were 
arranged  in  series  in  accordance  with  the  time  of  their  withdrawal 
and  were  permitted  to  clot,  after  which  the  serum  was  tested  with 
ferric  chlorid.  The  results  showed  that  the  solution  completed  the 
circuit  through  the  heart  and  carotid  arteries  in  from  20  to  30  seconds. 
Vierordt-  made  use  of  a  more  accurate  method  for  determining  the 
length  of  the  intervening  period  by  permitting  a  series  of  receiving 
cups  to  rotate  at  a  uniform  speed  below  the  vein.  Hermann  employed 
sodium  ferrocyanid  and  permitted  the  blood  to  drop  at  regular  inter- 
vals upon  paper  moistened  with  ferric  chlorid. 

1  Zeitschr.  fur  Physiol.,  iii,  1829. 

^  Erschein.  und  Gesetze  der  Stromgeschw.  des  Blutes,  Frankfurt,  1858. 


410    THE    MECHANICS    OF    THE    CIRCULATION,    HEMODYNAMICS 

The  circulation  time  for  this  particular  circuit  is:  6.6  seconds  in 
the  cat,  7.4  seconds  in  the  rabbit,  16.3  seconds  in  the  dog,  and  28.8 
seconds  in  the  horse.  For  man  the  time  for  the  completion  of  a  cir- 
cuit pf  medium  length  has  been  calculated  at  23  seconds  so  that  from 
26  to  28  beats  of  the  heart  are  required  to  effect  this  journey.  In 
other  words,  a  droplet  of  blood  traverses  the  circulatory  system  about 
three  times  in  every  minute. 

More  recently,  Stewart^  has  devised  a  method  which  is  based  upon 
changes  in  the  electrical  conductivity  of  the  blood.  The  carotid 
artery  is  coimected  with  non-polarizable  electrodes,  the  segment  be- 
tween them  being  inserted  as  a  resistance  in  one  arm  of  a  Wheatstone's 
bridge.  As  soon  as  a  balance  has  been  established  so  that  the  galvano- 
meter remains  at  rest,  a  solution  of  sodium  chlorid  is  injected  into  the 
external  jugular  vein  of  the  opposite  side.  This  salt  serves  the  purpose 
of  lessening  the  resistance  of  the  blood  to  the  electrical  current.  As 
soon  as  this  quality  of  blood  arrives  at  the  point  designated,  the  balance 
in  the  Wheatstone's  bridge  is  lost  and  the  galvanometric  needle  is 
deflected.  The  time  elapsing  between  the  injection  and  the  moment 
of  the  deflection  is  determined  by  means  of  a  stop-watch  or  an  ordi- 
nary chronographic  appliance.  Stewart-  has  also  employed  solutions  of 
methylene-blue  which  were  injected  into  the  external  jugular  vein  and 
were  rendered  visible  in  the  opposite  carotid  artery  by  means  of 
transillumination  upon  a  white  sheet  of  paper.  With  the  help  of  the 
first  method,  Stewart  has  also  determined  the  time  consumed  by  the 
blood  in  its  passage  through  various  organs.  In  the  case  of  the  spleen 
the  average  time  is  given  as  10. 95  seconds,  and  in  the  cases  of  the  kidneys 
and  lungs  as  13.3  and  8.4  seconds  respectively.  These  figures  show 
first  of  all  that  a  considerable  part  of  the  total  circulation  time  of  the 
blood  must  be  apportioned  to  the  capillary  networks  of  these  organs 
and  secondly,  that  the  time  for  the  pulmonary  circuit  is  relatively 
short.  In  man  it  has  been  estimated  at  12-15  seconds.  A  still 
shorter  time  is  required  for  the  completion  of  the  coronary  circuit. 
In  this  connection,  brief  mention  might  also  be  made  of  the  fact  that 
the  circulation  time  between  the  portal  vein  and  the  arteries  amounts 
to  about  12  seconds,  and  the  time  between  the  femoral  or  renal  veins 
and  the  arteries  to  16  and  13  seconds  respectively.^  These  figures 
have  been  obtained  by  measuring  the  interval  between  the  injection 
of  adrenalin  and  the  resultant  rise  in  arterial  blood  pressure. 

1  Jour,  of  Physiol.,  xv,  1894. 

2  Manual  of  Physiol.,  London,  1896. 

*  Burton-Opitz,  Am.  Jour,  of  Physiol.,  xli,  1916,  91. 


SECTION  XI 

THE  NERVOUS  REGULATION  OF  THE 
BLOOD-VESSELS^ 


CHAPTER  XXXIV 

THE  INNERVATION  OF  THE  BLOOD-VESSELS  OF  DIFFERENT 

ORGANS 

General  Discussion. — The  nervous  control  of 
the  vascular  system  is  effected  by  two  groups  of 
elements,  one  of  which  is  concerned  with  the  control 
of  the  activity  of  the  heart,  and  the  other  with  that 
of  the  caliber  of  the  blood-vessels.  The  former,  as 
we  have  seen,  are  acceleratory  and  inhibitory  in 
their  nature  and  are  dominated  by  nervous  ele- 
ments situated  in  the  medulla  oblongata.  The 
latter,  on  the  other  hand,  are  apportioned  to  the 
peripheral  vascular  system  and  regulate  the  size  of 
the  blood-bed.  For  this  reason  they  are  designated 
as  vasomotor  elements.  The  general  arrangement 
of  this  mechanism  is  the  same  as  that  controlling 
the  function  of  the  heart.  It  consists  of  a  central 
mass  of  ganglion  cells  and  of  two  sets  of  nerve  fibers 
which'  conduct  either  in  an  afferent  or  in  an  efferent 

1  Vershuir  (Diss.  Groningen,  1766)  observed  that  the  me- 
chanical excitation  of  the  walls  of  such  arteries  as  the  caro- 
tid and  femoral,  led  to  a  marked  constriction  of  their  lumen. 
Wedemeyer  (Kreisl.  des  Blutes,  Hanover,  1828)  obtained 
the  same  results  with  electrical  stimulation.  In  1831,  E.  H. 
Weber  (Archiv  fiir  Anat.  und  Physiol.,  1847)  explained  the 
phenomenon  of  flushing  and  paling  upon  the  basis  of  varia- 
tions in  the  resistance  to  the  blood  which  are  brought  about 
by  the  muscular  contractions  following  nervous  discharges. 
Claude  Bernard  (Compt.  rend.,  1851)  then  called  attention 
to  various  vascular  changes  connected  with  the  cutting  of 
the  cervical  sympathetic  nerve,  while  Brown-Sequard  (Phila- 
delphia Med.  Exam.,  Aug.,  1852)  ascertained  that  the  excita- 
tion of  the  proximal  stump  of  this  nerve  led  to  a  constriction 
of  the  blood-vessels.  Very  similar  results  were  obtained 
by  Waller  (Compt.  rend.,  1853),  but  their  publication  was 
deferred  until  1853. 

411 


Fig.  221.— Re- 
flex Circuit  for 
Vasomotor  Actions. 

R,  receptors;  A, 
afferent  path;  VMC, 
vasomotor  center 
which  is  intimately 
connected  with 
other  centers,  for 
example,  the  cardiac 
(CC)  and  respiratory 
centers  (RC);  E, 
efferent  path;  B, 
effector  in  blood- 
vessel. Stimulation 
between  fl  and  VMC 
gives  rise  to  pressor 
and  depressor 
effects,  stimulation 
between  VMC  and 
B  to  vasoconstrictor 
and  vasodilator 
effects. 


412        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

direction.  The  former  convey  impulses  from  all  parts  of  the  body  to 
the  center  and  the  latter,  from  the  center  to  the  blood-vessels  (Fig. 
221).  But  as  the  lumen  of  the  blood-vessels  may  be  either  decreased 
or  increased  in  size,  the  efferent  or  motor  path  must  be  composed  of 
two  types  of  fibers,  namely,  those  which  diminish  and  those  which 
enlarge  it.  The  former  are  designated  as  vasoconstrictors  and  the 
latter  as  vasodilators.  In  accordance  with  this  functional  division  of 
the  fibers,  it  is  possible  to  look  upon  the  vasomotor  center  as  being 
composed  of  a  vasoconstrictor  and  a  vasodilator  part. 

As  the  afferent  impulses  arriving  in  the  center  are  capable  of 
producing  either  a  vasoconstriction  or  a  vasodilatation,  the  fibers 
conducting  them  are  commonly  designated  as  pressor  and  depressor 
fibers.  Thus,  if  an  impulse  is  generated  either  in  the  center  or  along 
the  course  of  an  efferent  nerve,  and  produces  a  constriction  of  the 
blood-vessels,  the  reaction  is  spoken  of  as  a  vasoconstrictor  action. 
Again,  if  the  stimulation  of  the  same  constituents  of  the  vasomotor  arc 
leads  to  a  dilatation  of  a  certain  area  of  blood-vessels,  the  effect  is  said 
to  be  vasodilator  in  its  nature.  But,  if  the  stimulus  arises  in  a  re- 
ceptor or  along  the  course  of  an  afferent  nerve,  the  reaction  is  desig- 
nated as  pressor  if  constrictoiy,  and  as  depressor,  if  dilatory  in  its 
nature.  The  last  two  terms,  therefore,  signify  that  the  vascular  reac- 
tions have  been  brought  about  reflexly. 

The  Location  of  the  Vasomotor  Center. — Nerve  fibers,  regulating 
the  caliber  of  the  blood-vessels,  may  be  contained  in  almost  any 
nerve,  together  with  fibers  possessing  other  functions.  They  may  also 
be  grouped  in  such  large  numbers  that  they  fonn  individual  nerve 
strings  of  considerable  size.  But  whether  mixed  with  other  fibers 
or  pursuing  an  independent  course,  they  cannot  be  differentiated  from 
fibers  possessing  a  different  function  excepting  by  physiologic  means. 
In  other  words,  as  nerve  fibers  bear  no  special  points  of  difference  in 
their  appearance,  their  function  must  be  arrived  at  by  subjecting  them 
to  certain  physiological  procedm'es,  such  as  mechanical  and  electrical 
stimulation. 

It  is  a  well-known  fact  that  the  division  of  the  spinal  cord  in  the 
cervical  region  gives  rise  to  an  extensive  relaxation  of  the  blood- 
vessels and  a  fall  in  the  general  blood  pressure,  while  the  division  of 
the  nervous  system  above  the  upper  border  of  the  meduUa  remains 
without  effect.  From  this  it  may  be  inferred  that  the  separation  of 
the  peripheral  nerve  paths  from  the  brain  occasions  a  loss  in  the  tonus 
of  the  blood-vessels  ordinarily  imparted  to  them  by  ganglion  ceUs  situ- 
ated between  these  two  cuts.  Repeated  experimentation  has  finally 
led  to  the  localization  of  a  colony  of  cells  in  the  medulla  oblongata 
to  which  it  has  been  possible  to  ascribe  a  vasoconstrictor  activity.^ 
In  accordance  with  the  experiments  of  Dittmar,^  this  center  is  bilateral 
and  lies  about  the  middle  of  the  fourth  ventricle  in  the  tegmental 

^  Owsjannikow,  Ber.  d.  sachs.  Gesellsch.  d.  Wissensch.,  xxiii,  187L 
^Ber.  der  sachs.  Akad  der  Wissensch.,  math.  phys.  Klasse,  xxv,  1873. 


INNERVATION  OF  THE  HLOOD-VESSELS  OF  DIFFERENT  ORGANS       413 

region  near  tlie  nucleus  of  tlie  facial  nerve  and  the  superior  olivary 
body.  In  tlu^  rabbit  it  possesses  a  length  of  3  mm.  and  a  breadth  of 
■  1-1.5  mm.  A  general  vasodilator  center  has  not  been  definitely 
located  as  yet,  but  it  may  be  assumed  to  form  either  a  part  of  the  vaso- 
constrictor center  or  to  be  situated  in  its  immediate  vicinity. 

Secondary  centers  controlling  the  caliber  of  the  l)lf)od-vessels 
are  supposed  to  exist  at  different  levels  of  the  cord,  as  well  as  in  the 
sympathetic  system,  but  the  evidence  upon  which  this  statement  is 
based  is  not  very  conclusive.  Thus,  it  has  been  found  that  the 
tonicity  of  the  blood-vessels  is  retained  in  a  measure  even  after  they 
have  been  separated  from  the  central  nervous  system  and  that  their 
tonus  frequently  reappears  very  soon  after  the  division  of  the  cervical 
segment  of  the  spinal  cord. 

The  Activity  of  the  Vasomotor  Center. — Under  normal  conditions, 
the  activity  of  the  vasomotor  center  is  dependent  upon  an  influx  of 
extraneous  impulses.  The  sum  total  of  these  determines  the  tonicity 
and  the  dynamic  state  of  the  vascular  system.  Its  function  may  be 
continued  for  some  time  after  all  these  different  afferent  impulses 
have  been  shut  off,  but  naturally,  a  continued  absence  of  these  stimuli 
always  tends  toward  retrogression  and  functional  uselessness.  But, 
besides  these  "external"  impulses  which  are  conducted  to  it  by  way  of 
many  different  centripetal  nerves,  the  constituents  of  the  vasomotor 
center  are  also  influenced  by  ''internal"  stimuH,  such  as  arise  in 
consequence  of  changes  in  its  blood  supply  or  variations  in  the  gas 
content  of  the  blood. 

Thus,  if  the  carbon  dioxid  of  the  blood  is  increased,  as  can  readily 
be  done  in  a  curarized  animal  by  discontinuing  the  artificial  respiration, 
the  general  blood  pressure  will  be  seen  to  rise  gradually  until  it  attains 
a  height  much  above  normal.  The  pressure  usually  remains  at  this 
level  for  a  considerable  period  of  time,  but  declines  subsequently  on 
account  of  the  increasing  diastolic  tendency  of  the  heart.  This  rise 
is  occasioned  by  a  general  constriction  of  the  blood-vessels  which  is 
dependent  upon  the  direct  excitation  of  the  vasoconstrictor  center  by 
the  carbon  dioxid.  Eventually,  however,  the  contractions  of  the 
heart  lose  their  force,  because  the  continuous  supply  of  blood  poor  in 
oxygen,  reduces  its  strength  so  that  it  is  no  longer  able  to  act  against 
the  high  peripheral  resistance  occasioned  by  the  vasoconstriction. 
The  blood  pressure  then  falls  in  proportion  to  the  diminution  in  the 
energy  of  the  heart  and  obviously,  this  fall  must  result  in  spite  of  the 
fact  that  the  blood-vessels  remain  in  the  constricted  condition.  If 
the  dyspneic  or  asphyctic  condition  of  the  blood  is  now  lessened  by 
again  instituting  artificial  respiration,  the  heart  usually  regains  its 
vigor  within  a  short  time.  This  change  is  clearly  betrayed  by  a  rise 
in  the  blood  pressure  above  normal.  Presently,  however,  the  relaxa- 
tion of  the  blood-vessels  following  upon  the  restitution  of  the  vigor  of 
the  cardiac  contractions  permits  the  pressure  to  become  normal  again. 
Should  the  dyspnea  and  asphyxia  be  continued,  a  narcotic  and  para- 


414       THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

lytic  state  eventually  results  which  is  characterized  by  a  general  vas- 
cular depression  and  may  lead  to  the  death  of  the  animal. 

Verj^  similar  effects  may  be  obtained  by  temporarily  obstructing 
the  blood  supply  of  the  brain.  In  all  experiments  of  this  kind,  how- 
ever, it  is  advisable  to  deepen  the  narcosis  by  the  administration  of 
curare,  because  in  the  non-curarized  animal,  the  increased  respiratory- 
movements,  as  well  as  the  general  muscular  spasms  which  eventually 
occur  in  the  course  of  the  asphyxia,  must  tend  to  raise  the  blood  pres- 
sure and  to  interfere  with  the  effects  of  the  vasoconstriction.  It 
need  scarcely  be  emphasized  that  in  the  case  of  asphyxia,  the  constric- 
tor agent  may  be  either  a  lack  of  oxygen  or  a  superfluity  of  carbon 
dioxid. 

The  Distribution  of  the  Vasomotor  Fibers. — The  axons  derived 
from  the  cells  of  the  vasomotor  center  descend  in  the  cord  and  termi- 
nate at  different  levels  in  the  anterior  horn  of  the  gray  matter.  From 
here  connections  are  made  with  the  sympathetic  system  by  way  of  the 
rami  viscerales,  but  naturally,  as  these  bridges  exist  only  in  the  tho- 
racic and  sacral  regions  of  the  cord,  the  vasomotor  outpourings  must 
necessarily  be  restricted  to  these  spinal  segments.  It  has  also  been 
found  that  the  cerebrospinal  and  sympathetic  systems  are  connected 
with  one  another  by  way  of  several  of  the  cranial  nerves,  and  hence, 
it  is  possible  that  some  of  the  vasomotor  fibers  leave  the  central 
nervous  system  by  way  of  these  channels.  At  all  events,  it  must  be 
concluded  that  while  the  control  of  the  blood-vessels  is  in  last  analysis 
a  function  of  the  cerebrospinal  system,  it  is  eventually  transferred 
to  the  autonomic  or  sympathetic  system. 

After  the  spinal  neurons  have  entered  the  sympathetic  system  their 
impulses  are  conveyed  to  the  more  remote  ganglia  by  secondary  neu- 
rons which  in  turn  are  connected  with  the  blood-vessels  of  the  thoracic, 
abdominal  and  pelvic  organs.  The  blood-vessels  of  the  head  are 
reached  by  way  of  the  ganglia  of  the  thorax  and  the  cervical  sympa- 
thetic which  connects  the  latter  with  the  superior  cervical  ganghon. 
Obviously,  therefore,  the  fibers  conducting  vasomotor  impulses,  are 
typically  autonomic  and  form  such  important  paths  as  the  greater 
and  minor  splanchnic  nerves,  the  nervi  erigentes  and  the  cervical 
sympathetic.  There  are,  however,  many  blood-vessels  present  in  our 
body  which  do  not  he  directly  within  the  realm  of  sympathetic  nerves, 
but  are  innervated  by  cerebrospinal  nerves.  In  this  group  belong 
the  blood-vessels  of  the  anterior  and  posterior  extremities.  This 
innei-vation  is  made  possible  by  the  fact  that  some  of  the  fibers  leave 
the  sjTnpathetic  system  and  enter  the  cerebrospinal  nerves  where  they 
intermingle  with  others  pursuing  a  perfectly  straight  course  from  the 
spinal  gray  matter  to  the  periphery.  These  "recurrent"  fibers  form 
the  so-called  gray  rami  viscerales. 

To  summarize:  the  vasomotor  fibers  passing  out  from  the  chief 
center,  attain  the  first  sympathetic  ganglia  by  way  of  the  anterior 
roots  of  the  cord,  and  the  white  rami  viscerales  (Fig.  222).     Two  or 


INNERVATION  OF  THE  BLOOD-VESSELS  OF  DIFFERENT  ORGANS       415 


vmc 


throe  nourons  generally  cover  this  entire  distance.  They  form  the 
prefj;anglionic  patli.  Distaliy  to  these  ganglia,  tlic  fibers  constituting 
the  postganglionic  path,  either  continue  onward  to  different  parts  of 
the  sympatlieti(;  system,  or  reenter  the  spinal  roots  by  way  of  the  gray 
rami  communieantes  where  they  intermingle  with  other  efferent  and 
afferent  fibers  composing  the  different  spinal  nerves.  In  this  way,  even 
the  vasomotor  mechanisms  situated  in  the  domain  of  the  cerebrospinal 
nerves,  procure  a  sympathetic  innervation 
and  are  rendered,  therefore,  characteristic- 
ally autonomic. 

The  Location  of  the  Motor  End-organ 
or  Effector. — It  has  been  proved  histologic- 
ally that  the  walls  of  the  central  arteries 
contain  much  connective  tissue  and  only  a 
relatively  small  number  of  smooth  muscle 
cells.  In  the  peripheral  arteries,  on  the 
other  hand,  the  latter  are  much  more 
numerous  and  are  arranged  here  in  the 
form  of  a  massive  circular  (tunica  media) 
and  a  thin  longitudinal  layer  (tunica  ex- 
terna). No  muscle  tissue  is  present  in  the 
true  capillaries,  these  tubules  being  com- 
posed solely  of  fiat,  nucleated  epithelial 
cells  similar  to  those  found  in  the  intima  of 
the  arteries.  In  the  veins,  connective  tissue 
predominates,  while  the  muscular  units  are 
poorly  developed  and  not  organized.  Thus, 
it  happens  that  some  of  the  veins  possess 
no  muscle  cells  at  all,  while  others,  and 
especially  those  of  the  lower  extremities, 
are  equipped  with  only  a  very  thin  circular 
layer  of  these  cells. 

As  the  only  effector  present  in  the  vas- 
cular system  is  the  smooth  muscle  cell,  it 
must  be  clear  that  vasomotor  reactions 
must  be  restricted  to  those  channels  which 

are  actually  in  possession  of  these  elements,  namely  the  arteries  and 
certain  veins.  To  be  sure,  it  has  been  stated  by  Mall^  that  the  portal 
vein  receives  a  vasoconstrictor  supply  through  the  greater  splanchnic 
nerves,  but  these  results  have  been  shown  by  Burton-Opitz^  to  be 
based  upon  unsatisfactory  experimental  evidence.  Thompson,^  how- 
ever, has  found  that  the  stimulation  of  the  sciatic  nerve  in  dogs 
and  cats  produces  a  visible  constriction  of  the  veins  of  the  posterior 

lArchiv  fiir  Physiol.,  1892,  409. 
^  Am.  Jour,  of  Physiol.,  xxxvi,  1915,  32.5. 

3  Archiv  fur  Physiol.,  1893;  also  see:  Bancroft,  Am.  Jour,  of  Physiol.,  i,  1898, 
477. 


Fig.  222.  — Diagram  to 
Illt'strate  the  Path  Pursued 
BY  THE  Vasomotor  Fibers. 

SC,  spinal  cord;  PR,  its 
posterior  root ;  AR,  itvS  anterior 
root;  Sn,  spinal  nerve;  <S,  sjth- 
pathetic  ganglion;  B,  blood- 
vessel; preganglionic  path  in 
red;  VMC,  vasomotor  center 
P  (red)  white  ramus;  postgan- 
glionic path  in  blue;  P^,  di- 
rectly to  blood-vessel;  P,  re- 
current fiber,  reentering  spinal 
nerve  by  way  of  gray  ramus. 


416        THE    NERVOUS    KEGULATION    OF    THE    BLOOD-VESSELS 

extremities,  but  as  this  effect  is  inconstant  and  very  localized,  it  may 
have  an  indirect  cause.  Moreover,  while  Henderson^  has  found  that 
strips  of  veins  react  toward  solutions  of  adrenalin  in  the  same  man- 
ner as  segments  of  arteries,  this  evidence  cannot  be  considered  as  a 
direct  proof  of  the  existence  of  vasomotor  elements  in  the  veins. 
On  the  whole,  therefore,  this  question  seems  to  have  found  a  negative 
solution. 

As  far  as  the  capillaries  are  concerned,  it  has  been  shown  by  Strieker 
and  others'-  that  these  tubules  possess  a  certain  degree  of  contractility, 
but  it  appears  that  this  reaction  cannot  acquire  a  definite  dynamical 
value.  All  living  substance  exhibits  this  property  and  hence,  it  can- 
not be  denied  to  the  living  cells  of  the  capillaries.  Stimuli  brought  to 
bear  upon  them  must  result  in  a  rearrangement  of  their  contents 
and  a  possible  constriction  of  the  lumen  of  the  capillary.  This  re- 
action, however,  does  not  seem  to  be  of  central  origin,  but  appears  to 
be  elicited  solely  by  local  excitations.  In  this  connection  attention 
should  also  be  called  to  the  fact  that  the  capillary  blood-bed  may  be 
materially  altered  by  variations  in  the  tension  of  the  surrounding 
tissues.  Thus,  the  lumen  of  these  tubules  may  be  compressed  in 
consequence  of  the  contraction  of  the  numerous  smooth  muscle  cells 
which  are  widely  scattered  through  the  skin.  The  relaxation  of  these 
muscular  elements,  on  the  other  hand,  must  tend  to  widen  the  capillary 
blood-bed  and  to  grant  a  more  copious  blood-supply  to  the  cutaneous 
parts.  Reactions  of  this  kind  result  in  consequence  of  variations  in 
the  temperature  of  the  surrounding  air  as  well  as  in  consequence  of 
the  immersion  of  the  body  in  cold  or  warm  water.  The  influence  of 
these  muscular  elements  upon  the  injection  of  the  cutaneous  capil- 
laries can  scarcely  be  overestimated.  It  should  be  emphasized,  how- 
ever, that  we  are  not  deaUng  in  this  case  with  a  true  vasomotor 
phenomenon,  but  solely  with  a  direct  mechanical  action.  At  the 
same  time  it  must  be  granted  that  any  influence  causing  a  contrac- 
tion of  the  cutaneous  smooth  muscle  tissue,  would  be  prone  to 
produce  a  vasoconstriction  in  addition.  A  reverse  relationship,  how- 
ever, need  not  exist. 

•  In  view  of  the  evidence  here  presented,  it  seems  permissible  to 
conclude  that  true  vasomotor  actions  are  possible  only  in  the  arterial 
system.  Since  the  smooth  muscle  tissue  is  most  massive  in  the  arteri- 
oles, it  may  be  surmised  that  the  most  powerful  effects  of  this  kind  are 
obtained  at  the  arteriocapillary  junction.  This  segment  of  the  arterial 
system,  therefore,  gives  lodgment  to  the  gate  or  sluice  through  which 
the  blood  must  pass  in  order  to  reach  the  capillaries.  Consequently, 
the  size  of  this  orifice  must  determine  the  volume  of  the  arterial  escape 
as  well  as  the  vascularity  of  the  more  distant  capillary  networks. 
Excepting,  therefore,  certain  local  influences  in  the  shape  of  the  cuta- 
neous smooth  muscle  cells,  the  caliber  of  the  latter  is  determined 

1  Am.  Jour,  of  Physiol.,  xxiii,  1909,  345. 

^  Steinach  and  Kahn,  Pfltiger's  Archiv,  xlvii,  1903. 


INNERVATION  OF  THE  BLOOD-VESSELS  OF  DIFFERENT  ORGANS       417 

excliisivoly  by  the  quantities  of  blood  whicli  are  permitted  to  escape 
through  tiiis  gate. 

The  Nature  of  the  Reaction. — Two  views  are  held  regarding  the 
manner  in  wliich  vasomotor  changes  are  brought  about.  Thus,  it 
may  l)c  assumed  that  th(>  blood-vessels  are  constantl}^  kept  in  a  state  of 
tonicity  and  that  vasoconstriction  is  had  in  consequence  of  an  extra 
discharge  of  impulses  by  the  center,  while  vasodilatation  is  the  result 
of  a  loss  of  tonus  which  is  immediately  followed  by  a  passive  enlarge- 
ment of  the  blood-vessels.  For  this  reason,  the  former  condition  may 
be  regarded  as  an  augmentor  and  the  latter  as  an  inhibitor  phenome- 
non. A  condition  comparable  to  this  one  exists  in  the  heart,  where 
accelerator  and  inhibitor  impulses  are  played  against  one  another. 
The  second  theory  proposes  that  vasoconstriction  and  vasodilatation 
are  two  distinct  processes  resulting  in  consequence  of  the  activity  of 
two  separate  mechanisms. 

If  the  first  theory  is  accepted,  the  effector  need  not  possess  special 
structural  characteristics,  because  vasoconstriction  could  then  be 
assigned  to  the  contraction,  and  vasodilatation  to  the  extreme  relaxation 
of  the  circular  musculature.  But,  if  the  second  view  is  adhered  to, 
two  distinct  effectors  would  have  to  be  present,  namely,  one  for  vaso- 
constriction and  one  for  vasodilatation.  Regarding  the  former,  no 
difficult}^  need  arise,  because  it  could  justly  be  ascribed  to  the  con- 
traction of  the  circular  layer  of  muscle  cells.  Less  manifest  is  the 
vasodilator  mechanism,  because  the  only  other  available  element  is 
the  layer  of  smooth  muscle  cells  which  is  arranged  longitudinally  to 
the  lumen  of  the  blood-vessel.  In  the  absence  of  a  structurally  more 
definite  effector,  we  are  practically  forced  to  assume  that  these  cells 
accomplish  the  dilatation  either  alone,  or  through  an  interaction  with 
the  circular  coat. 

It  is  quite  impossible  at  the  present  time  to  decide  with  certainty 
whether  the  first  or  the  second  theory  is  the  correct  one.  The  evi- 
dence favoring  the  second  view,  namely,  that  the  vasoconstrictor  and 
vasodilator  reactions  are  effected  by  separate  mechanisms,  is  as 
follows : 

(a)  Certain  nerves  are  in  existence  which  possess  solely  a  dilator  function. 
First  among  these  is  the  chorda  tympani,  a  branch  of  the  facial  nerve,  which 
embraces  dilator  fibers  for  the  submaxillary  and  sublingual  glands,  as  well  as  the 
tympanic  branch  of  the  glossopharyngeal  nerve  which  contains  dilator  fibers  for  the 
posterior  third  of  the  tongue,  the  tonsils,  pharynx,  and  parotid  gland.  In  this 
group  should  also  be  placed  the  cervical  sympathetic  nerve,  by  way  of  which  the 
dilators  gain  access  to  the  mucous  membrane  of  the  lips,  gums,  palate  and  the  skin 
of  the  cheeks  and  nostrils.^  Some  direct  evidence  is  also  at  hand  to  prove  that  the 
abdominal  sympathetic  system  contains  nerves  of  this  kind.-  It  is  also  possible 
to  incite  dilator  effects  in  the  domain  of  the  nervi  erigentes,  by  waj^  of  which  the 
erectile  tissues  of  the  reproductive  organs  are  reached.  It  must  be  remembered, 
however,  that  the  tenseness  of  these  organs  is  not  caused  by  vasodilatation  alone, 

^  Dastre  and  Morat,  Red.  exper.  sur  le  systeme  nerv.  vasomoteur,  1884. 
^  Burton-Opitz,  Pfliiger's  Archiv,  cxxiii,  1908,  553. 

27 


418        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

but  also  by  an  actual  stagnation  of  the  blood  stream  which  results  in  consequence 
of  an  obstruction  to  the  venous  return.  The  latter  effect  is  made  possible  by  the 
contraction  of  circular  cushions  of  muscular  tissue  which  form  sphincters  at  the 
points  of  junction  between  the  venules  and  the  cavernous  blood  spaces. 

(6)  The  dilator  and  constrictor  reactions  may  be  dissociated  by  chemical  means. 
Thus,  it  has  been  found  by  Dale  Hhatergotoxin  possesses  the  property  of  paralyzing 
the  constrictor  mechanism,  so  that  the  stimulation  of  any  mixed  vasomotor  nerve 
must  give  way  in  time  to  dilatation.  It  is  also  possible  to  produce  vasomotor 
effects  solely  with  the  aid  of  chemical  agents  so  that  we  need  not  resort  to  the 
electrical  stimulation  of  a  nerve.  For  example,  adrenalin  in  very  small  doses 
dilates  the  blood-vessels  of  the  cutaneous  circuits,  while  larger  doses  give  rise 
to  a  constriction.  2  In  the  same  way,  it  has  been  found  that  proteoses  cause  a 
dilatation,  while  chrysotoxin  (ergot)  stimulates  the  constrictor  mechanism. 

(c)  The  constrictor  and  dilator  reactions  may  also  be  dissociated  by  changing 
the  temperature  or  by  changing  the  frequency  of  the  stimulation.  Thus,  Howell, 
Budget  and  Leonard^  have  shown  that  the  irritability  of  the  dilator  fibers  of  the 
sciatic  nerve  may  be  destroyed  sooner  than  that  of  the  constrictors  by  simply 
heating  or  cooling  the  nerve.  If  a  quickly  interrupteti  current  of  moderate  strength 
is  applied  to  a  nerve,  the  usual  result  is  vasoconstriction.  Bowditch  and  Warren,* 
however,  have  found  that  infrequent  electrical  stimuli  commonly  give  rise  to  a 
dilatation  instead  of  a  constriction.  In  the  case  of  the  renal  blood-vessels, 
Bradford^  employed  fifty  induction  shocks  at  intervals  of  one  second.  Very 
similar  results  have  been  obtained  with  the  greater  splanchnic  nerve,  by  Meltzer 
and  Auer,^  and  Burton-Opitz.''  The  infrequent  excitation  of  the  central  end  of  this 
nerve  gave  rise  to  reflex  vasodilatation  and  a  most  pronounced  fall  in  blood  pressure. 
It  might  also  be  mentioned  that  the  degeneration  following  the  division  of  the 
sciatic  nerve,  affects  the  constrictor  fibers  first  of  all,  so  that  vasodilator  effects 
may  be  obtained  for  some  time  after  its  constrictor  power  has  been  lost. 

The  Results  of  the  Reaction. — In  general,  it  holds  true  that  the 
division  of  a  nerve  containing  vasomotor  fibers  is  followed  by  a 
relaxation  of  the  blood-vessels  innervated  by  it.  The  vascular  area 
so  affected  loses  its  tonic  resistance  and  becomes  engorged  with  blood 
and  distinctly  warm  to  the  touch.  If  this  area  is  sufficiently  large,  these 
changes  must,  of  course,  react  upon  the  general  circulation  and  produce 
a  fall  in  the  general  pressure,  because  a  considerable  quantity  of  the 
systemic  blood  must  find  its  way  into  these  relaxed  vessels.  In  manj- 
cases  these  blood-vessels  regain  their  tonus  within  a  comparatively 
brief  period  of  time,  provided,  of  course,  that  they  are  still  in  connec- 
tion with  gangUonic  elements.  The  latter  are  capable  of  assuming  the 
function  of  those  chief  centers  with  which  they  were  previously  con- 
nected. This  is  especially  true  of  the  blood-vessels  situated  in  the 
realm  of  the  sympathetic  system,  because  this  system  embraces 
numerous  local  conglomerations  of  ganglion  cells  which  are  markedly 
independent  in  their  function  from  the  cerebrospinal  structures. 

Most  generally,  the  excitation  of  the  distal  end  of  a  divided  vaso- 

1  Jour,  of  Physiol.,  xlvi,  1913,  291. 

2  Hartman,  Am.  Jour,  of  Physiol.,  xxxviii,  1915,  438. 

3  Jour,  of  Phvsiol.,  xvi,  1894,  298. 
"  Ibid.,  vu,  1886,  416. 

6  Ibid.,  X,  1889,  358. 

6  Centralb.  fur  Physiol.,  1916. 

^  Am.  Jour,  of  Physiol.,  xlii,  1917,  498. 


INNERVATION  OF  THE  BLOOD-VESSELS  OF  DIFFERENT  ORGANS       419 

motor  nerve  with  currents  of  medium  strength  and  frequency  gives 
rise  to  a  vasoconstriction  in  the  part  innervated  by  it.  This  result 
may  also  be  obtained  by  stimulation  of  the  intact  nerve,  and  naturally, 
if  a  certain  nerve  is  composed  solely  of  dilator  fibers,  its  excitation 
must  be  followed  by  a  dilatation.  As  an  example  of  this  kind  might  be 
mentioned  the  chorda  tympani  which,  as  has  been  stated  above, 
consists  of  dilator  fibers  for  the  submaxillary  and  sublingual  glands. 

As  far  as  the  result  of  these  constrictor  reactions  is  concerned,  it 
must  be  evident  that  the  diminution  in  the  caliber  of  the  arterial 
terminals  must  reduce  the  arterial  throughflow.  This  change  is  asso- 
ciated with  an  increase  in  the  arterial  presure  and  a  decrease  in  th(! 
capillary  and  venous  pressures.  Conversely,  a  vasodilatation  must 
favor  a  greater  escape  of  blood  into  the  capillaries  and  occasion  a  fall 
in  the  arterial  and  a  rise  in  the  capillary  and  venous  pressures. 

It  has  previously  been  emphasized  that  the  vasomotor  mechanism 
is  the  chief  factor  concerned  in  the  production  of  the  peripheral  re- 
sistance, and  that  the  latter  in  turn  pla3's  a  most  important  part  in  the 
production  of  blood  pressure.  The  other  three  factors  are  the  energy 
of  the  heart,  the  total  quantity  of  the  blood,  and  the  elasticity  of  the 
blood-vessels.  Consequently,  the  blood  pressure  nmst  be  entirely 
dependent  upon  the  proper  interaction  of  these  four  values.  Thus,  it 
will  be  seen  that  the  effects  of  a  vasoconstriction  may  be  greatly  les- 
sened by  a  reduction  in  the  cardiac  output,  while  a  vasodilatation  may 
be  quite  offset  by  an  augmentation  of  the  action  of  the  heart.  This 
compensatory  phenomenon  is  indeed  a  very  common  one,  because  a 
high  blood  pressure,  resulting  in  the  course  of  a  general  vasoconstric- 
tion, is  usually  neutralized  by  a  reduction  in  the  cardiac  output.  But, 
it  may  also  happen  that  the  other  factors  act  in  perfect  unison  with  the 
vasomotor  mechanism  and  thus  occasion  an  exaggeration  of  the  vaso- 
motor effect.  For  example,  if  a  general  vasoconstriction  occurs  syn- 
chronously with  a  high  cardiac  rate,  a  rise  in  blood  pressure  must 
result  which  must  greatly  exceed  the  rise  produced  by  the  vasocon- 
striction alone. 

Nothing  further  need  be  said  regarding  the  pressor  and  depressor 
reactions.  Inasmuch  as  these  effects  are  brought  about  reflexly 
by  impulses  generated  in  different  parts  of  the  body,  the  vasomotor 
center  must  be  activated  first  before  these  impulses  can  be  transferred 
upon  the  efferent  channels.  One  or  the  other  of  these  effects  may  be 
elicited  either  by  stimulating  the  afferent  nerve  while  intact,  or  by 
dividing  it  and  using  its  central  end  for  the  stimulation.  Obviously, 
if  the  distal  end  of  a  nerve  of  this  kind  is  subjected  to  the  excitation, 
the  impulses  here  generated  cannot  reach  the  center  at  all  and  hence, 
no  pressor  or  depressor  effect  can  be  evoked.  As  a  typical  example  of 
a  depressor  nerve  might  be  mentioned  the  depressor  cordis,  the  stimu- 
lation of  which  produces  a  general  reflex  vasodilatation  and  a  most 
decided  fall  in  blood  pressure.  Similar  results  may  be  obtained  by 
the  excitation  of  the  splanchnic  nerve,  and  especially  if  currents  of 


420        THE    XERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

low  strength  and  frequency  are  employed.  In  fact,  pressor  and  de- 
pressor fibers  are  contained  in  many  nerves,  such  as  the  sciatic  and  the 
vagus,  but  their  presence  can  only  be  detected  by  the  stimulation  of 
the  central  ends  of  these  nerves  and  by  the  use  of  infrequent  shocks  of 
low  intensity. 

Methods  Used  to  Detect  Vasomotor  Action. — While  it  has  been 
possible  to  prove  histologically  that  the  walls  of  the  blood-vessels 
contain  nervous  structures,  this  fact  in  itself  is  not  sufiicient  to  show 
that  they  are  in  possession  of  vasomotor  elements.  In  other  words, 
the  only  definite  proof  of  vasomotor  activity  is  to  be  found  in  the  oc- 
currence of  the  reaction  itself.  We  may  resort  to  inspection,  because 
if  all  indirect  factors,  such  as  external  pressure,  have  been  ruled  out, 
the  blanching  of  a  part  may  justh^  be  referred  to  a  vasoconstriction 
and  its  reddening  to  a  vasodilatation.  These  alterations  in  the 
vascularity  are  usually  associated  wath  changes  in  temperature,  a  vaso- 
constriction occasioning  a  fall  and  a  vasodilatation  a  rise  in  the  tem- 
perature of  the  part.  Probably  the  most  direct  proof  of  vasomotor 
activity  may  be  obtained  with  the  help  of  the  recording  stromuhr, 
this  instrument  being  inserted  in  the  artery  or  vein  of  the  part  to  be 
experimented  upon.  As  has  been  stated  above,  this  instrument 
registers  the  volume  of  the  blood  stream  and  may  therefore  be  used 
to  see  whether  or  no  the  flow  is  affected  by  the  excitation  of  nerves  and 
other  expermiental  procedures.  A  decrease  in  the  arterial  supply 
would  then  betray  a  constrictor  action,  and  an  increase  a  dilator 
effect.  It  is  also  permissible  to  detect  these  vasomotor  changes  by 
making  a  simultaneous  record  of  the  pressure  in  the  artery  and  vein 
of  the  organ  to  be  examined.  A  mercurial  manometer  and  water 
manometer  are  employed  for  this  purpose.  Clearly,  a  rise  in  the 
arterial  and  a  fall  in  the  venous  pressure  would  betray  a  vasoconstric- 
tion, and  a  fall  in  the  arterial  and  a  rise  in  the  venous  pressure,  a 
vasodilatation.  These  changes  are  easily  explained,  because  the 
former  reaction  must  increase  and  the  latter  decrease  the  resistance 
to  the  arterial  throughflow.  The  manometer  is  also  used  to  detect 
vasomotor  effects  of  a  more  general  kind.  It  is  then  connected  with 
one  of  the  principal  arteries,  such  as  the  carotid  or  femoral.  A  rise  in 
the  general  pressure  may  then  be  attributed  to  a  constriction  of  an 
extensive  area  of  the  circulatorv^  system,  and  a  fall  in  the  general 
pressure  to  a  vasodilatation  of  rather  wide  extent.  Lastly,  it  js  pos- 
sible to  place  the  organ  to  be  experimented  upon  in  a  plethysmograph. 
Under  this  condition  a  diminution  in  the  volume  of  the  organ  would 
point  toward  a  vasoconstriction,  and  an  increase  in  its  volume  toward 
a  vasodilatation.  But  naturalh^,  if  these  procedures  are  practised, 
care  must  be  taken  to  exclude  all  indirect  effects,  such  as  may  be  pro- 
duced by  a  mechanical  obstruction  to  the  blood  flow.  An  occurrence  of 
this  kind  usually  leads  to  a  stagnation  of  the  blood  and  an  increase  in 
the  volume  of  the  organ  which  can  scarcely  be  differentiated  from  a 
true  vasomotor  effect. 


INNERVATION  OF  THE  BLOOD-VESSELS  OF  DIFFERENT  ORGANS       421 

SPECIAL  VASOMOTOR  REACTIONS 

The  Spinal  Cord. — As  the  spinal  cord  is  the  chief  highway  by 
means  of  which  the  vasomotor  center  in  the  medulla  stands  in  com- 
munication with  the  constrictor  and  dilator  mechanisms  of  the  blood- 
vessels, the  destruction  of  this  part  must  lead  to  a  pronounced  fall 
in  blood  pressure.  The  tonic  influences  of  the  higher  center  are  then 
prevented  from  reaching  the  periphery,  as  are  also  those  generated  in 
the  minor  centers  of  the  cord  itself.  In  other  words,  a  general  vascular 
relaxation  now  results  which  may  finally  produce  an  almost  complete 
stoppage  of  the  blood  flow.  The  animal,  so  to  speak,  is  bled  into  its 
own  highly  relaxed  vessels. 

A  fall  in  blood  pressure  may  also  be  produced  by  dividing  the  cord 
either  in  its  cervical  or  in  its  thoracic  region.  In  both  cases  the 
blood-vessels  innervated  by  those  nervous  elements  which  are  situated 
posteriorly  to  the  cut,  lose  their  tonus  and  relax.  It  is  to  be  noted, 
however,  that  this  relaxation  is  not  permanent,  because  the  lower 
spinal  centers  then  develop  a  tonic  power  independent  of  that  of  the 
rest  of  the  cord.  The  blood-vessels  gradually  regain  their  former 
caliber  and  enable  the  blood  pressure  to  return  to  a  value  approaching 
normal.  From  the  foregoing  data,  it  may  also  be  inferred  that  the 
excitation  of  the  peripheral  stump  of  the  spinal  cord  must  give  rise  to  a 
vasoconstriction  and  a  rise  in  the  general  blood  pressure,  because  the 
constriction  of  the  formerly  relaxed  blood-vessels  leads  to  the  trans- 
fer of  a  large  amount  of  previously  stagnated  blood  into  the  general 
circulatory  system.  The  stimulation  of  the  central  stump  of  the 
divided  spinal  cord  with  currents  of  ordinary  strength  sets  up  different 
reflexes  which  usually  result  in  a  pressor  reaction. 

The  Sciatic  Nerve. — This  nerve  must  be  considered  as  the  vaso- 
motor highway  of  the  posterior  extremity.  In  accordance  with  the 
preceding  analysis,  it  may  be  gathered  that  its  division  occasions  a 
relaxation  of  the  blood-vessels  innervated  by  it,  but  a  marked  reduction 
in  the  general  blood  pressure  cannot  result  in  consequence  of  this 
procedure,  because  the  extra  quantity  of  blood  which  finds  its  way  into 
the  circulatory  channels  of  the  leg,  is  not  sufficiently  large  to  affect 
the  d3mamic  conditions  in  the  general  circulation.  The  stimulation 
of  the  distal  stump  of  the  divided  sciatic  nerve  is  usually  followed  by  a 
constriction  of  the  peripheral  blood-vessels,  the  superfluous  amount  of 
blood  being  again  driven  into  the  general  circuits  of  the  body.  But 
this  transfer  remains  as  a  rule  without  decisive  effect  upon  the  general 
circulation  for  the  reason  just  given.  The  result  ordinarily  obtained 
upon  excitation  of  its  central  end  is  a  rise  in  blood  pressure,  but  this 
pressor  effect  may  be  changed  into  a  depressor  reaction  by  lessening  the 
frequency  and  intensity  of  the  stimuli.  The  foregoing  account  is  also 
applicable  to  other  spinal  nerves,  such  as  the  brachial. 

Our  knowledge  regarding  the  vasomotors  of  skeletal  muscle  tissue 
is  still  very  indefinite,  owing  to  the  difficulties  experienced  in  differ- 


422        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

entiating  between  the  nervous  effects  and  those  caused  bj'  the  contract- 
ing muscle  fibers.  Gaskell^  states  that  the  excitation  of  the  distal  end 
of  the  motor  nerve  of  the  mylohyoid  muscle  gives  rise  to  a  dilatation 
which  persists  even  after  the  administration  of  curare.  Besides,  the 
determinations  of  the  blood  supply  of  the  gracilis  muscle  of  dogs, 
which  have  been  undertaken  by  Burton-Opitz^  and  Tschucwskj',^ 
have  shown  that  the  flow  is  greatl}'  diminished  during  the  period  of 
contraction  of  the  muscle  but  much  increased  during  its  relaxation. 
It  need  scarcely  be  emphasized  that  these  changes  may  be  chieflj^ 
mechanical  and  must  occur  whenever  the  motor  nerve  of  a  muscle  is 
stimulated.  This  is  shown  by  the  fact  that  the  tetanization  of  the 
muscle  reduces  the  blood  flow  almost  to  zero.  We  have  no  means  of 
differentiating  between  these  mechanical  effects  and  those  of  vasomotor 
origin,  unless  we  should  paralyze  the  motor  plates  by  means  of  curare. 
But  again,  inasmuch  as  this  agent  might  also  affect  the  vasomotor  ter- 
minals in  muscle,  it  could  not  ser\'e  as  a  means  to  decide  this  question 
one  vrsLj  or  another.  This  uncertainty  regarding  the  existence  of 
vasomotor  nerves  in  muscle  tissue,  has  not  been  lessened  by  the  experi- 
ments of  Kaufmann,*  who  has  ascertained  that  the  blood  flow  through 
the  masseter  muscle  of  the  horse  may  be  increased  as  much  as  five  times 
by  permitting  this  animal  to  masticate  normalh'.  Instead  of  referring 
this  change  to  a  stimulation  of  the  nerv^ous  mechanism,  we  might 
attribute  it  with  equal  justification  to  a  mechanical  widening  of  the 
blood-vessels.  This  explanation  might  be  adhered  to  in  spite  of  the 
fact  that  this  action  is  associated  with  a  fall  in  pressure  in  the  artery 
supplying  this  muscle,  and  an  increase  in  pressure  in  the  vein  draining 
it. 

The  Trigeminus  Nerve. — This  nerv^e  embraces  vasoconstrictor 
fibers  for  the  conjunctiva,  the  sclerotic  coat  and  iris  of  the  eye,  as 
well  as  for  the  mucous  lining  of  the  nose  and  gums.  Its  hngual  branch 
innervates  the  blood-vessels  of  the  tongue.  In  the  rabbit,  the  auricu- 
laris  magnus  nerve,  a  branch  of  the  third  cervical,  embraces  vaso- 
motor fibers  for  the  ear. 

The  Cervical  S3mipathetic  Nerve. — This  nerve  forms  the  connec- 
tion between  the  inferior  and  superior  cervical  gangha.  During  its 
course  along  the  neck,  it  lies  in  relation  with  the  carotid  artery  and 
the  vagus  nerve.  In  some  animals,  such  as  the  rabbit,  it  pursues  an 
independent  course,  while  in  others  it  attaches  itself  to  the  vagal  fibers 
(cat)  or  becomes  complete!}-  intermingled  with  them  (dog).  Distally 
to  the  superior  cervical  ganglion,  the  individual  fibers  follow  in  the 
path  of  the  blood-vessels  and  finally  attain  such  structures  as  the 
cerebrum,  the  ear,  submaxillary  gland,  larynx,  thyroid  body,  and 
the  integument  of  the  head. 

1  Jour,  of  Physiol.,  i,  1878,  108. 

2  Am.  Jour,  of  Physiol.,  Lx,  1902,  161. 

3  Pfluger's  Archiv,  xcvii,  1903,  289. 
*  Arch,  de  Physiol,  et  Path.,  1892. 


INNERVATION  OF  THE  BLOOD-VESSELS  OF  DIFFERENT  ORGANS      423 


One  of  tlu'  most  strikiiifz;  vasomotor  reactions  obtainable  with  the 
aid  of  this  nerve  is  the  following;:  If  the  l)loo(l-vessels  in  the  ear  of  a 
rabbit  are  rendered  more  clearly  perceptible  by  transillumination,  it 
can  readily  be  observed  that  the  division  of  this  nerve  occasions  a  very 
decided  vascular  relaxation.  Many  blood-vessels  which  were  previ- 
ously quite  invisible  to  the  naked  eye;,  are  now  sharply  outlined,  and 
the  ear  on  the  operated  side  is  distinctly  warmer  than  the  one  on  the 
normal  side.  If  the  distal  (cephalic)  end  of  this  nerve  is  stimulated,  a 
vasoconstriction  soon  results  which  betrays  itself  most  unmistakably 
by  a  diminution  in  the  caliber  of  the  central  artery  and  its  principal 
branches.     These  vessels  grow  smaller  and  smaller  until  they  can 


Fig.  223. — The  Vasomotor  Reactions  in  the  Ear  of  the  Rabbit  on  Divi.sion 
AND  Stimulation  of  the  Cervical  Sympathetic  Nerve. 
A.  Normal.     B.  After  division  of  the  cervical  sympathetic  nerve.     C.  On  stimu- 
lation of  the  distal  end  of  the  divided  cervical  sympathetic  nerve. 

scarcely  be  made  out.  The  veins  remain  visible  for  a  much  longer 
time,  but  eventually  collapse  owing  to  the  cessation  of  the  arterial 
influx.  This  ear  now  feels  distinctly  colder  than  the  one  on  the  normal 
side.  On  discontinuing  the  stimulation,  the  arteries  again  relax  until 
they  have  attained  their  former  caliber.  These  changes  may  be  pro- 
duced again  and  again,  but  naturally,  only  at  intervals,  to  avoid  fatigu- 
ing this  vasomotor  mechanism. 

The  superior  cervical  ganglion  also  serves  as  the  distributing  center 
of  the  sympathetic  fibers  to  the  sublingual  and  submaxillary  glands. 
These  fibers  follow  in  the  course  of  the  art.  glandularis  submaxillaris. 
The  aforesaid  organs  also  receive  a  second  nerve  supply  which  is  de- 
rived from  the  bulbar  autonomic  system  and  appears  peripherally^  in 
the  form  of  a  small  nerve  known  as  the  chorda  tympani.  The  latter 
leaves  the  system  of  the  facial  nerve  and  attaches  itself  at  first  to  the 
lingual  nerve  of  the  fifth  system.     When  it  reaches  the  region  of  Whar- 


424       THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

ton's  duct,  it  turns  abruptly  and  attains  the  aforesaid  glands  by  way  of 
this  duct.  Under  ordinary  conditions  of  experimentation,  these  two 
sets  of  fibers  possess  an  antagonistic  action  upon  the  vascularity  of 
these  glands,  because  the  cerebral  nerve  or  chorda  tj^mpani  possesses 
vasodilator  and  the  sympathetic  nerve  vasoconstrictor  qualities.  The 
former  change  is  associated  with  a  secretion  of  a  large  quantity  of 
very  watery  saliva,  and  the  latter  with  a  scanty  production  of  a  very 
viscous  and  turbid  saliva.^ 

These  changes  may  be  studied  most  advantageously  in  a  dog  or 
large  cat.  The  stimulation  of  the  chorda  is  undertaken  as  a  rule  in  the 
triangle  where  this  nerve  leaves  the  Ungual  to  attach  itself  to  Wharton's 
duct.  The  excitation  of  the  sympathetic  may  be  accomplished  at 
any  point  of  its  course  along  the  neck,  but  as  the  vagal  and  sympathetic 
fibers  of  the  dog  intermingle,  it  becomes  necessary  to  apply  in  this  case 
the  electrodes  to  the  distal  (cephalic)  end  of  this  nei-ve.     It  should  be 


Fig.  224. — Schema  Illl-strati>,g  the  Xee\-e  Supply  of  the  Slbmaxillaey  Glaxd. 
SG,  submaxillary  gland;  supplied  by  a  small  aitery  from  the  carotid  system  (.CA). 
It  is  drained  by  a  small  vein  which  generally  enters  the  facial  (,FV)  at  its  point  of  con- 
fluence with  the  lingual  vein  (LV).  The  external  (ESV)  and  internal  (JSV)  maxillary 
veins  invest  the  gland  and  unite  to  form  the  external  jugular  vein  (EJV).  The  sympa- 
thetic nerve  supply  is  derived  from  the  sup.  cerv.  ganglion  (SCG).  The  chorda  tympani 
(CT)  attaches  itself  to  the  lingual  nerve  LiV  and  then  to  Wharton's  duct  Cir);AS,  lower 
jaw. 

remembered,  however,  that  we  are  concerned  at  this  time  solely  with 
the  aforesaid  vascular  reaction  and  not  with  any  other  effect  which 
this  stimulation  might  produce.  In  the  cat,  it  is  possible  to  isolate 
the  sympathetic  fibers  from  the  vagus  proper,  because  their  line  of 
contact  is  clearly  marked  by  a  small  blood-vessel.  If  the  surface  of 
the  submaxillary  gland  is  now  fully  exposed  to  the  view,  it  will  be  seen 
that  the  stimulation  of  the  chorda  causes  it  to  redden,  while  the  excita- 
tion of  the  (vago-)  sympathetic  causes  it  to  pale.  These  changes 
in  the  vascularity  of  this  organ  may  also  be  made  out  manometrically, 
or,  as  has  been  done  by  Burton-Opitz,^  by  means  of  the  stromuhr 
inserted  in  the  distal  end  of  the  external  jugular  vein.  In  the  latter 
case,  however,  all  tributary  veins  must  first  be  ligated  in  such  a  manner 
that  solely  the  blood  from  the  submaxillary  gland  is  enabled  to  enter 

1  Heidenhain  in  Hermann's  Handb.  der  Physiologie,  v,  1883. 
» Jour,  of  Physiol.,  xxx,  1903,  132. 


INNERVATION  OP  THE  BLOOD-VESSELS  OF  DIFFERENT  ORGANS       425 

this  instrument.  Quite  naturally,  the  excitation  of  the  chorda  tyrn- 
pani  then  f;ives  rise  to  an  augmentation  of  the  venous  pressure  and 
flow,  because  the  resulting  vasodilatation  allows  a  Q,reater  quantity 
of  arterial  blood  to  pass  through  this  gland.  The  stimulation  of  the 
sympathetic,  on  the  other  hand,  then  leads  to  a  diminution  in  the 
venous  pressure  and  flow,  because  the  vasoconstriction  immediately 
following,  serves  to  place  a  grcniter  resistance  in  the  path  of  the 
arterial  blood. 

The  superior  cervical  ganglion  is  also  connected  by  postganglionic 
fibers  with  the  blood-vessels  of  the  brain.  This  fact  has  been  demon- 
strated by  Jenson'  who  has  measured  the  venous  return  from  this 
organ  with  the  aid  of  a  stromuhr  inserted  in  the  external  jugular  vein. 
Under  this  condition,  the  stimulation  of  the  distal  end  of  the  cervical 
sympathetic  nerve  invariably  led  to  a  diminution  in  the  blood  flow 
through  this  vein.  The  fact,  that  the  cerebral  blood-vessels  are  equip- 
ped with  vasoconstrictor  powers,  has  also  been  established  by  Wiggers,^ 
who  measured  the  quantity  of  fluid  perfused  through  the  blood- 
vessels of  an  excised  brain  before  and  during  the  administration 
of  adrenalin.  Very  similar  reductions  in  the  cerebral  blood-supply 
have  also  been  incited  by  the  direct  stimulation  of  the  internal  carotid 
artery  at  the  point  where  it  enters  the  skull.  It  is  entirely  probable 
that  the  constrictor  fibers  follow  this  artery  in  their  course  to  intra- 
cranial parts.  Less  convincing  are  the  results  obtained  with  the  help 
of  the  plethj'-smograph,  but  several  observers  (Weber)  claim  to  have 
noted  certain  variations  in  the  volume  of  the  brain  which  could  not 
be  explained  in  any  other  way  than  by  assuming  that  this  organ  is 
innervated  by  constrictor  and  dilator  fibers. 

The  Greater  Splanchnic  Nerve. — This  nerve  embraces  those  fibers 
of  the  thoracic  outpouring  of  sympathetic  fibers  which  are  destined 
to  regulate  the  caliiier  of  the  blood-vessels  of  the  abdominal  organs, 
inclusive  of  the  kidneys,  adrenal  bodies,  stomach,  intestine,  hver, 
pancreas  and  spleen.  These  organs,  which  are  commonly  called 
the  splanchnic  organs,  are  not  reached  by  them  directly  but  only  by 
w^ay  of  several  relay  stations  forming  the  so-called  solar  plexus.  The 
latter  eftibraces  the  right  and  left  suprarenal,  and  the  mesenteric  and 
celiac  ganglia.  The  connection  between  these  and  the  organs  just 
enumerated,  is  effected  by  several  postganglionic  paths,  such  as  the 
renal,  mesenteric,  splenic,  celiac  and  hepatic  plexuses. 

The  point  to  be  especially  emphasized  at  this  time  is  that  these 
nerves  control  the  blood  supply  of  extremely  large  and  vascular  struc- 
tures and  possess,  therefore,  an  almost  dominating  influence  upon  the 
distribution  of  the  total  quantity  of  the  circulating  blood.  This 
statement  can  be  substantiated  by  the  following  simple  experiment. 
If  the  general  blood  pressure  is  recorded  by  means  of  a  mercurial  mano- 
meter connected  with  the  carotid  artery,  it  will  be  seen  that  the  di- 

1  Pfliiger's  .\rchiv.,  ciii,  1904,  195. 

2  Am.  Jour,  of  Physiol.,  xiv,  1905,  and  xxi,  1908. 


426        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

vision  of  the  right  or  left  splanchnic  nerve  leads  in  the  course  of  a 
few  moments  to  a  marked  diminution  in  the  pressure.  This  effect 
may  be  rendered  even  more  conspicuous  by  dividing  both  nerves. 
If  the  distal  (abdominal)  end  of  this  nerve  is  now  stimulated  with  a 
current  of  moderate  strength  and  duration,  it  will  be  noted  that  the 
systemic  blood  pressure  rises  rather  abruptly  and  remains  high  for 
some  time  after  the  cessation  of  the  stimulation.  All  vasomotor  reac- 
tions, however,  develop  slowly,  for  the  reason  that  smooth  muscle 
cells  do  not  contract  so  rapidly  as  the  striped  variety.  Neither  is 
it  possible  to  continue  an  experiment  of  this  kind  for  any  considerable 
length  of  time,  because  it  is  eventually  cut  short  by  fatigue.  It  has 
been  mentioned  above  that  the  excitation  of  the  central  (thoracic) 


Fig.  225. — Record  of  the  Cabotid  Blood-pressure  in  Rabbit  During  Stimulation 
OF  THE  Left  Greater  Splanchnic  Ner\t. 

end  of  this  nerve  with  currents  of  low  frequency  and  strength  gives 
rise  to  a  general  vasodilatation  and  fall  in  the  systemic  blood  pressure. 
In  explaining  this  reaction  it  should  be  borne  in  mind  that  the  di- 
vision of  the  splanchnic  nerve  is  soon  followed  by  a  relaxation  of  the 
blood-vessels  innervated  by  it.  Consequently,  a  steadily  increasing 
quantity  of  blood  must  leave  the  systemic  channels  and  become  lodged 
in  those  of  the  splanchnic  organs.  In  some  animals,  this  transfer 
of  blood  may  lead  to  circulatory  disturbances  which  actually  endanger 
their  life.  At  all  events,  the  fall  in  gener^al  pressure  resulting  from  the 
engorgement  of  the  splanchnic  blood-vessels,  eventually  gives  rise 
to  cerebral  anemia  and  various  symptoms,  such  as  vertigo,  mental 
lethargy  and  muscular  weakness.  Conditions  constantly  arise  in  our 
system  which  require  extra  amounts  of  blood  to  be  transferred  from 
place  to  place  and  especially  when  the  digestive  organs  are  actively 
engaged  in  reducing  and  absorbing  the  food.  This  means  that  they 
must  be  supplied  with  larger  quantities  of  blood  which,  on  being  with- 


THE    CIRCULATION    THROUGH    SPECIAL    ORGANS  427 

drawn  from  the  systemic  circuit,  genorall}^  give  rise  to  mental  and 
bodily  fatigue.  These  symptoms  are  also  observed  whenever  th(^ 
tonicity  of  the  splanchnic  blood-vessels  is  lost  in  consequence  of  general 
nervous  debility,  irritation  of  the  intestines,  and  other  conditions. 

Concurrently,  it  may  be  gathered  that  the  stimulation  of  the  distal 
end  of  the  greater  splanchnic  nerve  must  occasion  a  transfer  of  blood 
from  the  splanchnic  area  into  the  general  circulation,  because  the 
vasoconstriction  resulting  in  consequence  of  this  procedure,  forces 
a  large  quantity  of  blood  out  of  these  channels  into  the  veins  and  the 
general  circuit  and  prevents  at  the  same  time  a  corresponding  influx 
of  arterial  blood.  The  systemic  blood  pressure,  therefore,  is  rapidly 
increased,  but  naturally,  this  augmentation  cannot  exceed  physiolog- 
ical limits,  because  while  the  arterial  blood  does  not  find  free  access  to 
the  splanchnic  organs,  it  is  still  in  a  position  to  leave  the  arterial  chan- 
nels by  way  of  the  carotid  and  femoral  arteries.^  Thus,  while  the 
stimulation  of  the  splanchnic  nerve  lessens  the  flbw  through  the  organs 
innervated  by  it,-  the  circulatory  conditions  in  the  central  venous 
system  remain  practically  unaltered. 

The  Depressor  Nerve. — The  function  of  this  nerve  has  been  de- 
scribed in  detail  in  one  of  the  preceding  chapters  (page  329).  It  is 
a  sensory  nerve  and  conducts  impulses  from  the  heart  to  the  cardiac 
and  vasomotor  centers.  Its  function  is  to  produce  a  general  reflex 
vasodilatation,  and  therefore  a  fall  in  the  systemic  blood  pressure.  In 
the  nature  of  things,  this  effect  can  only  be  obtained  by  the  stimulation 
of  either  the  intact  nerve  or  of  its  central  or  cephalic  stump.  It  has 
been  stated  above  that  marked  depressor  effects  may  also  be  obtained 
with  the  help  of  the  thoracic  sympathetic  nerve  and  its  branches. 


CHAPTER  XXXV 

THE  CIRCULATION  THROUGH  SPECIAL  ORGANS 

A,  THE  CORONARY  CIRCULATION 

In  man  the  orifice  of  the  right  coronary  artery  is  situated  in  the 
anterior  sinus  of  Valsalva,  whence  this  blood-vessel  passes  forward 
and  follows  the  right  auriculoventricular  groove  until  it  reaches  the 
interventricular  groove.  At  this  point  it  divides  into  two  branches, 
the  smaller  of  which  continues  onward  in  the  left  auriculoventricular 
groove,  and  the  larger  in  the  inferior  interventricular  groove.  The 
left  coronary  artery  arises  from  the  left  fossa  of  Valsalva  and,  passing 
backward,  divides  at  the  left  auricular  appendix  into  two  branches, 

1  Edwards,  Am.  Jour,  of  Physiol.,  xxxv,  1914,  15. 

2  Burton-Opitz,  Quart.  Jour,  of  Exp.  Physiol.,  iv,  1912,  83. 


428        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

one  of  which  descends  along  the  anterior  interventricular  groove  to 
the  apex  of  the  heart,  while  the  other  follows  the  left  auriculoventricu- 
lar  groove.  From  these  superficial  blood-vessels,  forming  what  is 
known  as  the  extramural  system,  branches  are  given  off  which  pene- 
trate the  substance  of  the  heart  and  by  repeated  division  give  rise  to 
the  so-called  intramural  system. 

The  cardiac  veins  follow  in  the  course  of  the  arteries,  uniting 
eventually  in  the  coronary  sinus  which  is  about  one  inch  in  length 
and  occupies  the  inferior  extremity  of  the  left  auriculoventricular 
groove.  It  empties  into  the  right  auricle  in  front  of  the  inferior  caval 
opening,  its  orifice  being  guarded  b}^  the  valve  of  Thebesius. 

In  this  connection  it  should  be  recalled  that  the  hearts  of  those 
lower  forms,  which  are  not  in  possession  of  an  independent  circulation, 
obtain  their  nutritive  material  directly  from  the  blood  as  it  traverses 
the  cardiac  chambers.  Many  of  these  organs  also  contain  irregular 
tubular  passages  which  penetrate  the  musculature  and  thus  enable 
the  blood  to  come  into  contact  with  even  the  most  remote  cells.  A 
similar  arrangement  is  present  in  the  mammaUan  heart.  Numerous 
openings,  the  so-called  foramina  of  Thebesius,  establish  a  communica- 
tion with  a  system  of  tubules  which  ramify  below  the  endocardial 
membrane,^  but  the  nourishment  which  the  mammalian  heart  is  able  to 
derive  from  this  source  is  not  sufficient  for  its  metabolic  requirements.  ^ 

That  the  activity  of  the  mammahan  heart  is  actually  dependent 
upon  the  coronary  blood  supply,  may  readily  be  gathered  from  the 
fact  that  an  isolated  and  quiescent  organ  may  be  made  to  beat  again 
by  instituting  an  artificial  circulation  through  its  coronarj^  circuit. 
In  fact,  the  frequency  and  force  of  the  cardiac  contractions  invariably 
go  hand  in  hand  with  the  pressure  under  which  the  perfusion  is  made. 
Very  similar  results  may  be  obtained  at  times  with  the  heart  of  the  cat. 
Thus,  if  its  aortic  orifice  is  occluded,  it  ceases  to  beat  almost  imme- 
diately, but  may  be  made  to  contract  again  by  filling  its  chambers 
with  defibrinated  blood  under  a  pressure  of  about  75  mm.  Hg.  This 
procedure,  however,  is  not  so  reliable  as  the  perfusion  through  the 
coronary  arteiy.  This  fact,  that  it  resumes  its  activity  under  these 
circumstances,  might  also  be  explained  upon  the  basis  that  the  cat's 
heart  possesses  a  more  extensive  system  of  direct  nutritive  channels 
than  that  of  other  mammals.  The  ligation  of  the  coronary  arteries 
in  the  dog  is  followed  almost  immediately  by  a  diminution  in  the 
rate  and  force  of  the  heart  beat  and  eventually  by  a  complete  stoppage. 
In  fact,  Parker  has  shown  that  the  occlusion  of  one  of  its  branches, 
namely  the  circumflex  artery,  suffices  to  arrest  the  heart  in  about 
80  per  cent,  of  the  animals. 

While  the  superficial  cardiac  vessels  are  protected  in  a  measure 
by  the  visceral  layer  of  the  pericardium,  as  well  as  by  connective 
tissue  and  fat,  the  deeper  branches  are  directly  exposed  to  the  power 

1  Pratt,  Am.  Jour,  of  Physiol.,  i,  1898,  86. 
^Langendorff,  Pfliiger's  Archiv,  Ixi,  1895,  291. 


THE    CIKCULATION    THROUGH    SPECIAL    ORGANS  429 

of  the  musculature.  It  nood  not  sui-priso  us,  thercforo,  to  find  that  the 
nuH'hani(;al  influences  thus  exerted  upon  tlie  blood  stream  play  an 
important  part  in  the  flow  throujih  this  system  of  vessels.  In  fact, 
much  uncertainty  has  always  prevailed  regarding  the  manner  and  the 
time  during  which  the  coronary  blood-vessels  are  filled.  Briicke/  for 
example,  has  expressed  the  id(^a  that  the  heart  possesses  a  self-regula- 
tory mechanism  wherel)y  tlu;  circulation  through  this  organ  is  made  to 
differ  in  certain  particulars  from  that  through  other  parts  of  the  body. 
As  the  orifices  of  the  coronary  arteries  are  situated  behind  the  flaps  of 
the  aortic  valve,  the  claim  has  been  made  that  these  openings  are  com- 
pletely closed  during  each  ventricular  systole-  and  that  the  heart  ob- 
tains its  supply  of  blood  only  during  the  diastolic  period  when  these 
valve  flaps  are  in  the  position  of  closure.  This  mode  of  filling  seemed 
the  more  likely,  because  the  relaxation  of  the  cardiac  muscle  must  exert 
a  favorable  influence  upon  the  influx  of  the  aortic  blood,  while  its 
contraction  must  force  the  blood  onward  into  the  veins  and  right 
auricle. 

This  view,  however,  has  found  no  substantiation,  because  it  has 
been  proved  by  iMartin  and  Sedgwick,^  as  well  as  by  Porter,"*  that  the 
pressure  changes  in  the  coronary  arteries  coincide  very  closely  with 
those  occurring  in  the  systemic  circuit.  Aloreover,  Rebatal^  has 
shown  that  the  coronary  blood  flow  suffers  an  acceleration  at  the 
beginning  of  each  sj^stole,  but  ceases  as  soon  as  the  musculature  has 
attained  a  state  of  maximal  contraction.  A  second  augmentation 
in  the  flow  is  said  to  result  during  diastole  which,  however,  soon  suffers 
a  retardation  in  consequence  of  the  gradual  filling  of  the  right  auricle. 
These  data  prove,  on  the  one  hand,  that  the  coronary  circuit  remains 
in  free  communication  with  the  aorta  even  during  the  systole  of  the 
heart  and,  on  the  other,  that  the  contracting  musculature  exerts 
a  powerful  pressure  upon  the  intramural  blood-vessels  which  greatly 
favors  their  emptjang.  In  further  substantiation  of  this  statement 
it  might  be  mentioned  that  if  a  piece  of  ventricle  is  made  to  beat 
rhythmically  by  perfusing  it  with  a  nutritive  fluid  through  its  artery, 
a  jet  of  blood  is  forced  from  the  distal  venous  orifice  with  every 
contraction  (Porter). 

The  question  whether  the  coronary  circuit  is  equipped  with  a 
vasomotor  mechanism  has  not  been  decided  as  3^et,  because  any 
attempt  to  solve  this  problem,  either  by  measuring  the  blood  flow 
directly  or  by  determining  the  changes  in  pressure,  must  be  seriously 
hampered  by  the  mechanical  action  of  the  contracting  musculature. 
Neither  is  it  possible  to  obtain  more  accurate  data  by  stimulation  of 
the  efferent  nerves  of  the  heart,  because  the  vagal  and  sympathetic 

1  Der  Verschluss  der  Kranzschlagadem  durch  die  Aorten  Klappen,  Wien, 
1855. 

^  A  statement  generally  attributed  to  Thebesius  (1708). 
3  Jour,  of  Physiol.,  iii,  1880,  165. 
*  Am.  Jour,  of  Physiol.,  i,  1898,  71. 
5  Dissertation,  Paris,  1872. 


430   THE  NERVOUS  REGULATION  OF  THE  BLOOD-VESSELS 

fibers  modify  the  rate  and  force  of  the  heart  in  such  a  degree  that 
it  becomes  quite  impossible  to  recognize  pure  vasomotor  changes. 
For  this  reason,  much  stress  cannot  be  placed  upon  the  experiments 
of  Parker^  and  Maas^  who  measured  the  outflow  from  the  coronary 
veins  of  isolated  hearts  of  cats  while  these  organs  were  being  perfused 
through  their  coronary  arteries.  Under  these  conditions,  the  excitation 
of  the  vagus  led  to  a  diminution  and  the  stimulation  of  the  sympathetic 
fibers  to  an  increase  in  the  flow.  In  accordance  with  the  foregoing 
statement,  we  are  not  justified  in  attributing  the  former  effect  to  a 
vasoconstriction  and  the  latter  to  a  vasodilatation. 

For  the  same  reason  no  definite  conclusions  can  be  drawn  from 
the  observations  of  N.  Martin,^  showing  that  the  stimulation  of  the 
vagus  produces  an  enlargement  of  the  smaller  blood-vessels  situated 
in  the  surface  layers  of  the  heart  and  that  a  dilatation  of  these  channels 
results  early  during  the  state  of  asphyxia,  when  the  general  blood 
pressure  preserves  as  yet  a  perfectly  normal  value.  Schafer,^  as  well  as 
Wiggers,^  is  of  the  opinion  that  the  changes  following  the  stimulation 
of  the  cardiac  nerves  during  perfusion  may  be  explained  more  satis- 
factorily by  attributing  them  to  other  than  vasomotor  influences. 
It  has  been  reported,  however,  that  the  coronary  vessels  of  the 
quiescent  heart  constrict  in  response  to  adrenalin,  and  that  this  agent 
increases  the  flow  through  this  organ  by  modifying  the  character  of 
its  contractions. 

B.  THE  PULMONARY  CIRCULATION^ 

The  dynamical  factors  which  are  responsible  for  the  flow  of  the  blood 
through  the  lesser  circuit,  present  the  same  general  characteristics  as 
those  previously  discussed  in  connection  with  the  greater  circuit.  The 
pressure  in  the  pulmonary  artery  finds  its  origin  in  the  activity  of  the 
right  ventricle.  As  the  driving  force  developed  by  this  chamber 
is  relatively  shght,  it  cannot  surprise  us  to  find  that  the  entire  pul- 
monary circulation  is  carried  on  with  the  aid  of  a  rather  low  pressure 
and,  hence,  with  a  lesser  expenditure  of  energy,  than  the  systemic. 
But  this  statement  is  not  meant  to  imply  that  the  pulmonary  circula- 
tion is  less  effective,  but  merely  to  suggest  that  the  low  pressures  here 
prev^ailing,  are  made  possible  by  the  fact  that  the  resistance  in  this 
circuit  is  very  slight.  That  this  deduction  is  correct  may  be  gathered 
from  the  observation  that  the  pulmonary  arterioles  possess  a  larger 
caliber  and  are  equipped  with  only  a  scanty  amount  of  smooth  muscle 
tissue. 

The  blood-vessels  of  the  lungs  are  constantly  undergoing  passive 

1  Boston  Med.  and  Surg.  Jour.,  1896. 

2  Pfiuger's  Archiv,  Ixxiv,  1899,  281;  also  see:  Dogiel  and  Archangelski,  ibid., 
cxvi,  1907,  482. 

3  Transact.,  Med.  and  Chir.  Fac.  of  Maryland,  1891. 
''  Arch,  des  sciences  biol.,  xi,  Suppl.,  1899. 

6  Am.  Jour,  of  Physiol.,  xxiv,  1909,  391. 

^  Discovered  by  Servet  and  Columbo  during  the  middle  of  the   16th  century. 


THE    CIRCULATION    THROUGH    SPECIAL    ORGANS  431 

variations  in  their  caliber  in  eonsequencc  of  the  respiratory  movements 
of  the  thorax.  They  are  witlened  during  normal  inspiration  and 
compressed  durinji;  exjiiration.  This  leads  us  to  infer  that  the  througii 
flow  is  greatest  tluring  tiu^  former  phase,  l)(;caus(!  tiie  n^sistanee  is 
least  at  this  time.  But  if  the  lungs  are  distended  artificially  through 
the  trachea,  these  conditions  are  reversed,  because  their  inflation  with 
air  produces  a  compivssion  of  their  blood-vessels.  The  peripheral 
resistance  is  increased  during  the  inflation.  C'onversely,  it  may  be  con- 
cluded that  the  deflation  of  these  organs  enables  the  vessels  to  acquire 
their  previous  caliber.  This  change  is  associated  with  a  diminution 
in  the  peripheral  resistance.^  As  has  previously  been  noted,  these 
rhythmic  variations  in  the  conditions  inside  the  thorax  play  an 
important  part  in  the  production  of  the  respiratory  oscillations  in 
blood  pressure.  Attention  should  also  be  called  at  this  time  to  the 
fact  that  the  vascularity  of  the  lungs  is  subject  to  the  conditions  pre- 
vailing in  th{^  heart.  Any  momentary  excess  in  the  venous  influx 
must,  of  course,  be  accommodated  by  the  distended  pulmonary  chan- 
nels until  the  heart  is  again  capable  of  propelling  it.  A  hyperemia  of  a 
more  permanent  kind,  however,  must  result  whenever  the  left  ventricle 
is  unable  to  relieve  the  lungs  of  a  normal  quantity  of  blood.  A  con- 
dition of  the  kind  must  arise  during  stenosis  or  regurgitation  of  the 
mitral  or  aortic  valves.  The  lesser  circuit,  therefore,  is  capable  of 
acting  as  a  resei-voir,  the  purpose  of  which  is  to  equalize  the  flow 
through  the  heart. 

The  measurements  of  the  pressure  and  flow  in  the  pulmonary 
artery  meet  with  serious  difficulties,  because  the  insertion  of  a  cannula 
in  tliis  blood-vessel  or  in  any  of  its  branches  necessitates  in  many 
animals  the  opening  of  the  pleurae  and  a  temporary  blocking  of  the 
pulmonary  circulation.  In  rabbits,  however,  it  is  possible  to  gain 
free  access  to  the  heart  by  simply  dividing  the  sternum  in  the  median 
Une.-  As  the  pleural  sacs  do  not  quite  reach  to  this  line,  they  need 
not  be  opened  and  artificial  respiration  need  not  be  resorted  to.  Beut- 
ner^  has  given  the  following  values  which  have  not  been  materially 
changed  in  more  recent  years: 

Dog 28-31  mm.  Hg 

Cat 15-19  mm.  Hg 

Rabbit 9-17  mm.  Hg 

These  figures  harmonize  completely  with  the  fact  that  the  right  ven- 
tricle develops  much  lower  pressures  than  the  left,  without,  however, 
causing  the  usual  systoUc-diastoHc  differences  to  disappear.  But  as 
the  latter  show  oscillations  of  only  about  15  mm.  Hg,  as  against  30- 
40  mm.  Hg  in  the  systemic  circuit,  their  range  is  rather  limited.     In 

1  Tigerstedt,  Ergebnisse  der  Physiol.,  ii,  2,  1903;  also  see:  Burton-Opitz,  Am. 
Jour,  of  Physiol.,  xxxvi,  1914,  64. 

-  Knoll,  Sitzungsber.,  Ak.,  Wien,  xcvii,  207,  1888. 

3  Zeitschr.  fiir  rat.  Med.,  N.  F.,  ii,  Ser.,  1882;  also  see:  Bradford  and  Dean, 
Proc.  Royal  Soc,  London,  1889,  and  Schafer,  Quart.  Jour,  of  Exp.  Physiol.,  xii, 
1919,  133. 


432        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

general,  therefore,  it  may  be  said  that  the  pressure  in  the  pulmonary 
blood-vessels  is  retained  at  a  more  constant  height,  amounting  to 
about  one-fifth  of  that  generally  obtained  in  such  arteries  as  the  car- 
otid and  femoral. 

In  this  connection  it  should  be  remembered  that  the  heart  and 
large  vessels  are  not  fully  exposed  to  the  atmospheric  pressure,  but  to 
the  atmospheric  pressure  less  the  elastic  pull  or  recoil  of  the  lungs. 
Furthermore,  this  force  must  be  of  greater  consequence  in  the  case  of 
the  soft  veins  than  in  that  of  the  more  sohdly  built  arteries.  With 
the  glottis  opened,  the  resph'atory  surface  of  the  lungs  is,  of  course, 
fully  exposed  to  the  atmospheric  pressure.  In  the  second  place,  it 
should  be  remembered  that  the  inspiratory  movements  increase  this 
negative  pressure  in  the  thorax  and  tend,  therefore,  to  augment  the 
aspiratory  action  upon  the  central  blood-vessels.  Tiiis  accounts  for 
the  fact  that  the  pulmonary  vessels  are  more  fully  dilated  during 
inspiration  and  offer  at  this  time  a  lesser  resistance  to  the  through 
flow  of  the  blood.  ^ 

The  velocity  of  the  flow  thi'ough  the  lungs  is  much  greater  than  that 
through  the  vessels  of  the  systemic  circuit.  It  has  been  found  that 
about  one- fifth  of  the  total  circulation-time  is  used  up  in  the  passage 
of  the  blood  through  this  organ.  Stewart,-  for  example,  has  shown 
that  the  average  time  required  by  the  blood  to  complete  its  journey 
from  the  right  to  the  left  side  of  the  heart,  amounts  to  8.7  seconds  in 
a  dog  weighing  about  12  kg.  and  to  10.4  seconds  in  a  dog  weighing 
about  18  kg.  If  apphed  to  man,  these  figures  indicate  that  the 
circulation-time  for  the  pulmonaiy  circuit  is  about  15  seconds. 

The  existence  of  vasomotors  in  the  lungs  is  still  an  open  question, 
because  theu'  recognition  ls  made  difficult  by  the  fact  that  satisfactory 
test  conditions  cannot  easily  be  established.  Whether  the  animal  be 
made  to  respire  normally  (rabbit)  or  artificially  (dog),  the  constant 
mechanical  action  of  the  lungs  upon  the  blood-vessels  must  neces- 
sarily tend  to  destroy  any  variations  in  the  pressure  and  flow  of  a 
true  vasomotor  kind.  Furthermore,  this  difficulty  cannot  be  overcome 
by  keeping  the  lungs  distended  with  a  constant  current  of  air,  nor  is 
it  possible  to  improve  the  experimental  conditions  by  perfusing  the 
quiescent  organs  with  a  nutritive  fluid.  In  either  case,  the  puhnonary^ 
circulation  cannot  be  considered  as  being  carried  on  under  conditions 
at  aU  comparable  to  normal. 

The  foregoing  statement  explains  in  a  way  the  diversity  of  the 
results  obtained.  Bradford  and  Dean,^  for  example,  have  decided 
in  favor  of  the  existence  of  pulmonarj^  vasomotors,  their  conclusions 
being  based  upon  differential  records  of  the  blood  pressm-e  in  the  car- 
otid and  pulmonary  arteries  during  stimulation  of  the  third,  fourth  and 

1  DeJager,  Pflliger's  Archiv,  xxvii-xxxix,  187^1886. 

2  Jour,  of  Physiol.,  xv,  1894,  1. 
» Ibid.,  xvi,  1894,  34. 


THE    CIRCULATION    THKOUGH    SPECIAL    ORGANS  433 

fifth  thoracnc  spinal  nerves.  Brodie  and  Dixon,'  on  the  other  hand, 
deny  their  i>resenee,  and  state  that  the  excitation  of  the  vagus  or 
sympathetic  nerve  does  not  cause  a  significant  alteration  in  the  rate 
of  perfusion  through  an  isohitetl  hmg.  Similar  results  have  been  ob- 
tained by  Burton-Opitz,2  who  measured  the  blood  flow  in  the  pulmo- 
nai-y  artery  with  the  aid  of  the  stromuhr.  The  use  of  adrenalin 
has  failed  to  decide  this  matter  one  way  or  another.  In  the  hands  of 
the  investigators  just  named,  this  agent  has  given  negative  results, 
while  Plumier^  has  found  that  the  flow  through  a  perfused  lung  may  be 
diminished  by  adrenalin.  A  diminution  in  the  flow  is  also  said  to 
follow  the  stimulation  of  those  sympathetic  fibers  which  pass  between 
the  first  thoracic  ganglion  and  the  pulmonaiy  plexus.  It  is  conceded, 
however,  that  the  changes  so  obtained  are  sHght  and  not  absolutely 
constant.  This  result  serves  as  an  argument  against  an  active  be- 
havior of  the  pulmonary  blood-vessels,  because  true  vasomotor  reac- 
tions are  always  of  an  amplitude  which  makes  the  use  of  very  delicate 
means  for  their  detection  superfluous. 

C.  THE  PORTAL  AND  RENAL  CIRCULATIONS 

The  portal  system  embraces  those  abdominal  organs  which  drain 
their  blood  into  the  vena  portse,  a  large  venous  tube  formed  by  the 
union  of  the  venm  mesentericce  and  the  vena  gastrolienalis.  Before  this 
channel  enters  the  hilus  of  the  liver  it  receives  another  vein  of  consider- 
able size,  namely  the  vena  pancreatica.  Centrally  to  the  liver,  the 
blood  is  conducted  into  the  inferior  vena  cava  by  the  hepatic  veins. 
As  the  name  indicates,  the  mesenteric  veins  return  the  blood  from  the 
intestines,  while  the  gastrolienalis  collects  it  from  the  spleen  and  the 
largest  part  (left)  of  the  stomach.  The  remaining  portions  of  this 
organ,  as  well  as  the  principal  mass  of  the  pancreas  and  the  middle  and 
upper  segments  of  the  duodenum,  are  drained  by  the  pancreatic  vein.* 

The  arterial  supply  of  these  organs  is  obtained  first  of  all  from  the 
celiac  axis  which  divides  into  three  branches,  namely:  (a)  the  hepatic 
artery  which  supplies  the  framework  of  the  liver,  the  body  of  the  pan- 
creas, and  the  adjacent  portion  of  the  duodenum,  (h)  the  gastric  artery 
which  ramifies  upon  the  right  expanse  of  the  stomach,  and  (c)  the 
splenic  artery  which  passes  to  the  spleen,  the  cauda  of  the  pancreas 
and  the  neighboring  left  segment  of  the  stomach.  The  intestine 
receives  its  blood  from  the  superior  and  inferior  mesenteric  arteries. 

The  organs  just  enumerated  are  innervated,  on  the  one  hand,  by 
the  vagi  nerves  and,  on  the  other,  by  the  greater  and  lesser  splanchnic 
nerves.     The  former  terminate  in  the  region  of  thegastro-esophageal 

1  Jour,  of  Phvsiol.,  xxx,  1904,  476. 

2  Proc.  Soc.  of  Exp.  Med.  and  Biology,  1904. 

'  Jour,  de  physiol.  et  de  pathol.  generate,  vi,  1904. 

■*  This  description  applies  to  the  dog.  More  complete  data  maj'^  be  obtained 
from  EUenberger  and  Baum's  Anatomie  des  Hundes,  Berlin,  1891. 

28 


434       THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

junction,  where  the  united  ventral  vagus  forms  the  plexus  gastricus 
anterior,  and  the  dorsal  vagus,  the  plexus  gastricus  posterior.  Both 
plexuses  are  intimately  connected  with  one  another  by  fibers  and  com- 
municate with  the  abdominal  ganglia  of  the  sympathetic  system  by 
direct  rami  to  the  plexus  suprarenalis.  The  plexus  gastricus  ventralis 
also  gives  off  fibers  which  pass  along  the  lesser  curvature  of  the  stom- 
ach and  eventually  ramify  upon  the  pylorus  where  they  unite  with  the 
plexus  hepaticus. 

It  is  a  well-known  fact  that  the  vagi  nerves  convey  musculo- 
motor  and  sensory  impulses  to  and  from  the  stomach  and  the  other 
organs  of  the  abdomen.^  They  do  not,  however,  seem  to  possess  a 
true  vasomotor  function.  It  should  be  mentioned  at  this  time  that 
the  excitation  of  the  vagus  frequently  produces  very  decided  reduc- 
tions in  the  blood  supply  of  the  stomach  and  intestine,  which  are  not 
due  to  the  inhibition  of  the  heart  nor  to  an  active  constriction  of  the 
blood-vessels,  but  are  dependent  upon  the  peristaltic  motion  invariably 
eUcited  by  the  stimulation  of  this  nerve.  The  influence  of  the  inhib- 
itor action  of  the  vagus  upon  the  heart  and  blood  flow  may  be  avoided 
by  simply  stimulating  this  nerve  at  any  point  below  this  organ  or 
by  administering  an  adequate  amount  of  atropine  to  paralyze  the 
inhibitor  mechanism.  The  perseverance  of  these  vascular  changes, 
even  after  these  precautionary  measures  have  been  taken,  must 
lead  us  to  conclude  that  the  contraction  of  the  gastric  apd  intestinal 
walls  lessens  the  size  of  the  blood-bed  and  thus  diminishes  the  blood 
flow  in  a  perfectly  mechanical  manner. 

The  vagi,  however,  form  a  most  important  afferent  path  by  means 
of  which  the  organs  of  the  abdomen  are  connected  with  the  central 
nervous  system.  They  are  concerned,  therefore,  with  the  production 
of  numerous  reflex  actions,  such  as  (a)  the  inhibition  of  the  heart ^  in 
consequence  of  strokes  upon  the  region  of  the  stomach  (plexus  Solaris), 
(6)  the  systemic  vasomotor  and  cardiac  disturbances  occasioned  by 
chemical  and  mechanical  irritation  of  the  intestine,  (c)  the  referred 
symptoms  accompanying  inflammatory  reactions  in  any  part  of  the 
abdominal  cavity,  and  others. 

Like  the  vagi,  the  splanchnic  nerves  are  efferent  and  afferent  in 
their  function.  They  form  the  connection  between  the  thoracic  and 
abdominal  ganglia  of  the  sympathetic  system.  Beginning  at  the 
ganglion  stellatum,  a  number  of  fibers  pass  downward  along  the  spinal 
column  to  be  constantly  augmented  by  fibers  derived  from  the  differ- 
ent spinal  nerves  (Fig.  226).  Opposite  the  thirteenth  rib,  this  nerve, 
which  is  known  as  the  thoracic  sympathetic,  divides  into  the  splanch- 
nicus  major  and  the  sympatheticus  abdominalis.  The  former  pierces 
the  diaphragm  and  passes  toward  the  adrenal  body,  where  it  ramifies 
extensively,  forming  here  the  so-called  plexus  suprarenalis.     The  lat- 

^  Burton-Opitz,  Pfliiger's  Archiv,  cxxxv,  1910,  205. 

^  As  we  are  here  concerned  solely  with  reflexes  upon  the  circulatory  system, 
the  accompanying  inhibition  of  the  respiratory  action  is  not  considered  at  this  time. 


THE    CIRCULATION    THROUGH    SPECIAL   ORGANS 


435 


ter,  on  the  othor  hand,  continues  to  pursue  a  course  along  the  spinal 
column  where  it  soon  receives  branches  from  the  lumbar  portion  of 
the  spinal  cord.  Their  points  of  union  are  marked  by  the  luml)ar 
ganglia.  The  first  three  of  these  give  rise  to  the  splanchnici  minores, 
which  pass  directly  across  toward  the  suprarenal  plexus.  The  ab- 
dominal sympathetic  continues  downward  and  eventually  connects 
with  the  sacral  nerves  and  the  sympathetic  system  of  the  pelvis. 
The  left  and  right  suprarenal  plexuses,  therefore,  may  be  regarded 
as  the  outposts  of  the  abdominal  sympathetic  system.  In  addition 
to  these  two  plexuses,  the  latter  includes  the  more  centrally  situated 
ganglion  mesentericum  superior  and  the  ganglion  celiacum.  All 
these  ganglia  together  with  their  extensive  network  of  fibers  and  a  few 


Fig.  226. — Diagr-Vnematic  Representation  of  the  Splanchnic  System  (Solar  Plexus). 
T,  thoracic  sj'mpathetic  nerve  di\'ides  into  {S)  greater  splanchnic  nerve  and  {A), 
abd.  symp.  nerve.  The  former  ends  in  the  suprarenal  plexus  (B)  and  the  latter  in  the 
lumbar  ganglia  (,LG).  From  the  lumbar  ganglia  the  three  minor  splanchnic  nerves 
pass  to  the  supraienal  plexus.  M,  Superior  mesenteric  and  C  celiac  ganglia  of  the  solar 
plexu?.  The  plexuses  leading  out  from  here  are:  /,  renal  plexus  to  kidney  (A');  II, 
mesenteric  plexus  to  intestine  (J) ;  ///,  hepatic  plexus  to  liver  (L)  stomach  (St),  pancreas 
(P)  and  duodenum  (£>).  IV,  gastro-splenic  plexus  to  spleen  (Sp)  and  stomach  (St); 
Di,  line  of  diaphragm. 

scattered  small  ganglia,  form  the  so-called  plexus  Solaris.  Thus,  the 
splanchnic  nerves  constitute  the  preganglionic  paths  and  the  different 
nerves  which  connect  the  solar  plexus  with  the  aforesaid  organs  of  the 
abdomen,  the  postganglionic  paths. 

The  Vasomotors  of  the  Kidneys  and  Suprarenal  Bodies. — These 
organs  do  not  belong  to  the  portal  system,  because  their  blood  is 
drained  directly  into  the  inferior  vena  cava,  but  as  they  are  innei*\^ated 
by  the  splanchnic  nerves,  they  may  be  conveniently  included  in  this 
discussion.  In  fact,  it  is  customarj^  to  speak  of  those  organs  which 
derive  their  nerve  supply  from  the  splanchnic  nerves,  as  forming  the 
splanchnic  system.  This  includes  the  portal  organs,  kidneys  and 
suprarenal  bodies.  Each  kidney  is  innervated  by  fibers  which  are 
derived  from  the  suprarenal  plexus  and  reach  this  organ  by  following 
the  highway  of  the  renal  artery.     They  form  the  so-called  plexus 


436        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

renalis,  which  in  turn  communicates  with  the  mesenteric  ganghon. 
By  measuring  the  blood-supply  of  this  organ  with  the  aid  of  the 
stroniuhr,  Burton-Opitz^  has  shown  that  the  stimulation  of  this  plexus, 
or  of  single  nei'ves  thereof,  leads  to  a  constriction  of  its  blood-vessels 
and  therefore  to  a  diminution  in  its  vascularity.  This  plexus  also 
contains  dilator  fibers.  The  same  results  may  be  obtained  by  the 
excitation  of  the  greater  splanchnic  nerve  of  the  same  side  or,  as  Brad- 
ford^  has  shown,  by  the  stimulation  of  the  fibers  emerging  from  the 
tenth  to  the  thirteenth  spinal  nerves  (dog).  This  investigator  also 
states  that  the  kidney  receives  dilator  fibers  which  are  derived  from 
the  eleventh,  twelfth  and  thirteenth  thoracic  spinal  nerves. 

By  cutting  the  renal  plexus  the  Iddney  is  converted  into  a  passive 
organ.  The  renal  blood-vessels  relax  and  permit  a  greater  quantity 
of  blood  to  enter  this  organ;  moreover,  this  augmentation  becomes  the 
more  pronounced,  the  greater  the  arterial  blood  pressure.  Thus,  the 
vascularity  of  a  denervated  kidney  can  be  increased  very  readily  by 
the  stimulation  of  either  splanchnic  nerve,  because,  as  we  have  seen, 
the  ensuing  constriction  of  the  portal  blood-vessels  raises  the  systemic 
blood  pressure  and,  hence,  also  the  arterial  influx  into  this  now  non- 
resistant  organ.  The  stimulation  of  the  central  end  of  the  divided 
renal  plexus  usually  gives  rise  to  a  reflex  increase  in  the  general  blood 
pressure  (pressor  action),  whereas  weak  and  infrequent  stimuli  gen- 
erally produce  a  reflex  vasodilatation  (depressor  action).  It  should 
also  be  remembered  that  the  innervation  of  the  kidneys  is  unilateral.^ 

That  the  splanchnic  nerves  are  capable  of  exerting  a  true  vasomotor 
influence  upon  the  adrenal  bodies  has  not  been  thoroughly  estabhshed.^ 
Certain  evidence,  however,  has  been  presented  by  Elliott^  and  Von 
Anrep^  to  show  that  they  govern  the  secretory  activity  of  these  glands. 
Thus  it  was  found  that  the  stimulation  of  the  aforesaid  nerves  gives 
rise  to  an  immediate  outpouring  of  adrenin  into  the  venae  suprarenales, 
whence  this  product  reaches  the  general  arterial  circulation  by  way  of 
the  inferior  cava.  Here  it  incites  its  characteristic  reaction  consisting 
in  a  general  vasoconstriction.  The  time  which  elapses  between  the 
moment  of  the  stimulation  of  the  splanchnic  nerve  and  the  beginning 
of  this  vasomotor  reaction,  amounts  to  about  12  to  15  seconds,  in  a  dog 
weighing  about  15  kg. 

This  outpouring  of  adrenal  substance  is  a  constant  physiological 
process,  tending  to  preserve  the  vasomotor  tonus  and  to  cause  tem- 
porary increases  in  blood  pressure.  Keeping  this  fact  clearly  in  mind, 
we  are  now  in  a  position  to  consider  more  fully  the  influence  which  the 
stimulation  of  the  splanchnic  nerve  exerts  upon  the  general  blood 

1  Pflliger's  Archiv,  cxxiii,  1908,  553. 

2  Jour,  of  Physiol.,  x,  1889,  358. 

3  Burton-Opitz,  Am.  Jour,  of  Physiol,  xl,  1916,  437. 

^  Biedl,  Pfluger's  Archiv,  Ixvii,  1897,  433 ;  also :  Burton-Opitz  and  Edwards, 
Am.  Jour,  of  Physiol,  xliii,  1917,  408. 

5  Jour,  of  Physiol,  xUv,  1912,  374. 

6  Ibid.,  xlv,  1912,  307. 


THE    CIRCULATION    THROUGH    SPECIAL    ORGANS  437 

pressure  as  well  as  upon  (.he  blood  How  t.hi'ou{>li  the  kiflne.ys.  Wo 
have  just  seen  (hat  (he  exeitadon  of  this  nerve  leads  not  only  to  a 
constiietion  of  the  blood-vessels  in  the  corresponding  kidney,  bat  also 
to  a  liberation  of  an  extra  amount  of  adrenin  from  the  n(!if>;hborinK 
suprarenal  Ixuly.  As  soon  as  this  agent  has  reacthed  the  arterial  system, 
a  general  vasoconstriction  is  incited  which  also  includes  the  blood- 
vessels of  the  two  kidneys.  But,  as  the  renal  blood-vessels  on  the 
side  of  the  stimulation  have  already  been  constricted  in  a  direct  way, 
the  adrenhi  only  serves  the  purpose  of  augmenting  the  pi'imary  effect 
in  (his  i)articular  organ.  On  the  opposite  side,  on  the  other  hand,  it 
incites  its  characteristic  effect.  Thus,  it  will  be  seen  that  the  stimula- 
tion of  the  splanchnic  nerve  eventually  leads  to  a  constriction  of  the 
vessels  of  both  kidneys,  but  the  one  occuring  on  the  side  of  the  excita- 
tion appears  almost  innnediately  after  the  make  of  the  current  and  is 
hie  primarily  to  a  direct  motor  influence,  whereas  the  one  in  the 
opposite  organ  takes  place  later  on  and  is  the  result  of  the  ingress  of 
adrenin. 

In  the  second  place,  we  are  now  in  a  position  to  offer  a  detailed 
explanation  of  the  character  of  the  rise  in  the  general  blood  pressure 
invariably  following  the  stimulation  of  the  splanchnic  nerve.  It  has 
been  observed  by  Johansson^  that  this  increase  does  not  present  a  single 
summit,  but  two,  the  initial  one  being  somewhat  smaller  than  the 
second.  ElUott  and  Von  Anrep  have  succeeded  in  showing  that  the 
second  elevation  is  dependent  upon  the  outpouring  of  adrenin,  because 
the  Ugation  of  the  suprarenal  veins  or  the  removal  of  the  suprarenal 
bodies  as  a  whole  causes  this  summit  to  disappear  completely.  To 
summarize:  Under  ordinary  experimental  conditions  the  stimulation 
of  the  splanchnic  nerve  produces  a  vasoconstriction  in  the  organs  in- 
nervated by  it.  The  transfer  of  blood  associated  therewith  relieves 
the  splanchnic  organs  of  a  certain  quantity  of  blood  and  forces  it 
into  the  general  circulation.  This  change  gives  rise  to  the  primary 
rise  in  the  arterial  blood  pressure.  Secondly,  it  also  leads  to  the  libera- 
tion of  adienin  which,  on  being  flushed  into  the  arterial  system,  causes 
a  general  vasoconstriction  which  is  associated  with  an  augmentation 
of  the  constriction  ah'eady  produced  in  the  splanchnic  organs.  In 
consequence  of  this  extensive  secondary  involvement  of  the  blood- 
vessels, the  general  blood  pressure  is  again  raised.  The  second  summit 
of  the  splanchnic  rise  in  blood  pressure  is  therefore  directly  attributable 
to  the  discharge  of  adrenin. 

The  Vasomotors  of  the  Intestines. — With  the  exception  of  the 
upper  segment  of  the  duodenum  the  intestine  is  innervated  by  fibers 
arising  in  the  mesenteric  ganghon  of  the  solar  plexus.  These  fibers 
pass  along  the  mesenteric  arteries.  The  stromuhr  experiments  of 
Burton-Opitz^  have  shown  that  the  division  of  this  postganglionic 
path  is  followed  by  an  engorgement  of  the  intestinal  blood-vessels, 

1  Archiv  fiir  Anat.  und  Physiol.,  1891,  103. 

2  Pfliiger's  Archiv,  cxxiv,  1908,  469. 


438        THE    NERVOUS    REGULATION    OF    THE   BLOOD-VESSELS 

and  that  the  stimulation  of  the  intact  plexus,  or  of  its  distal  end,  gives 
powerful  vasoconstrictor  effects.  It  has  also  been  established  that 
this  plexus  conducts  afferently,  because  the  excitation  of  its  central 
stump  produces  a  pressor  reaction.  The  same  results  may  be  obtained 
by  the  stimulation  of  either  splanchnic  nerve;  hence,  the  intestine  is 
innervated  bilaterally.  Moreover,  Francois-Frank  and  HalUon^  claim 
that  this  preganglionic  path  embraces  dilator  fibers  for  this  organ. 

The  Vasomotors  of  the  Stomach. — ^These  fibers  ascend  from  the 
celiac  gangUon  of  the  solar  plexas  and  follow  in  the  paths  of  the  three 
branches  of  the  celiac  axis.  By  measuring  the  venous  return  from  this 
organ,  Burton-Opitz^  has  shown  that  its  left  side,  as  well  as  the  region 
along  the  greater  curvature,  is  innei'vated  by  fibers  which  are  derived 
from  the  plexus  gastrolienalis  surrounding  the  artery  of  the  same  name. 
Its  pyloric  portion,  as  well  as  the  region  of  the  lesser  curvature,  is 
mnervated  by  the  plexus  accompanying  the  arteria  epiploica  dextra, 
while  the  pylorus  proper  receives  its  vasomotor  supply  by  waj'  of  the 
plexus  hepaticus  and  the  plexus  gastroduodenaUs.  By  stimulation 
of  the  aforesaid  nerves,  it  was  possible  to  obtain  most  decided  reduc- 
tions in  the  blood  supply  of  this  organ.  The  same  results  followed 
the  stimulation  of  the  splanchnic  nerves.  The  vasomotor  nerves  for  the 
upper  and  middle  segments  of  the  duodenum  are  also  derived  from 
the  ceUac  ganghon.  These  fibers  ascend,  together  with  those  for  the 
pylorus,  by  way  of  the  hepatic  plexus  and  the  plexus  gastroduodenaUs.^ 

The  Vasomotors  of  the  Spleen. — These  fibers  are  contained  in  the 
plexus  gastrolienalis  which  closely  invests  the  artery  of  the  same  name. 
By  determining  the  blood  flow  through  this  organ  by  means  of  the 
stromuhr,  it  has  been  shown  by  Burton-Opitz'*  that  the  stimulation 
of  this  plexus  is  followed  by  a  constriction  of  the  splenic  blood-vessels. 
The  same  i-esult  is  obtained  by  stimulation  of  either  splanchnic  nerve, 
Schaffer,^  who  has  made  use  of  a  splenic  oncometer,  states  that  this 
preganghonic  path  includes  vasodilators  for  this  organ. 

The  Vasomotors  of  the  Pancreas. — These  fibers  arise  in  the  celiac 
gangUon  and  attain  the  aforesaid  organ  by  way  of  the  plexus  hepaticus 
and  the  plexus  gastroduodenalis.  It  seems,  however,  that  the  caput 
pancreatis  is  also  innervated  by  fibers  from  the  mesenteric  plexus,  and 
that  the  cauda  pancreatis  receives  fibers  from  the  neighboring  splenic 
plexus.  As  far  as  the  blood-vessels  in  the  central  mass  of  this  organ 
are  concerned,  it  has  been  shown  by  Burton-Opitz^  that  they  are  in- 
nerv'ated  by  fibers  which  ascend  from  the  celiac  ganglion  by  way  of 
the  hepatic  plexus  and  the  plexus  gastroduodenalis. 

The  Vasomotors  of  the  Liver. — This  organ  derives  its  blood  supply 
from  two  som-ces,  namely,  from  the  hepatic  artery,  a  branch  of  the 

1  Archiv  de  Physiol.,  1896,  493. 

^  Pfliiger's  Archiv,  cxxxv,  1908,  205. 

3  Burton-Opitz,  Am.  Jour,  of  Physiol.,  cxlvi,  1914,  344. 

4  Pfliiger's  Archiv,  cxxix,  1908,   189. 

5  Jour,  of  Physiol.,  xx,  1896. 

6  Pfluger's  Archiv,  cxlvi,  1908,  344. 


THE    CIRCULATION    THROUGH    SPECIAL    ORGANS  439 

celiac  axis,  and  from  the  portal  vein.  TIk;  former  blood-vessel 
conveys  its  contents  to  the  framework  of  this  organ  and  the  latter  to 
the  secretory  colls.  It  is  a  well-known  fact  that  the  arterial  terminals 
eventually  unite  with  the  intralol)ular  radicles  of  the  portal  vein,  so 
that  })oth  ty])(>s  of  blood  eventually  attain  the  common  collecting  tube, 
the  vena  hepatica.  For  this  reason,  it  must  be  evident  that  the  schtc- 
toiy  cells  of  the  different  acini  cannot  be  rendered  absolutely  bloodless 
by  the  ligation  of  the  portal  vein,  because  a  certain  amount  of  blood 
will  still  ho.  furnished  them  in  an  indirect  way  by  the  hepatic  ai'tery. 
In  agreement  with  the  histological  evidence,  Burton-Opitz'  has  found 
that  the  influx  through  the  hepatic  arteiy  is  always  increased  if  the 
portal  blood  is  prevented  from  reaching  the  liver  by  diverting  it  directly 
into  the  inferior  vena  cava  through  a  fistulous  communication  (Eck 
fistula). 

The  manometric  determinations  of  Burton-Opitj^  have  shown 
that  the  pressure  in  the  hepatic  artery  of  the  dog  is  from  4  to  6  mm. 
Hg  lower  than  that  prevailing  in  the  abdominal  aorta,  and  from  5  to 
6  mm.  Hg  higher  than  that  existing  in  the  arteria  gastroduodenalis. 
The  latter  blood-vessel,  as  has  been  stated  previously,  forms  the  con- 
tinuation of  the  hepatic  artcr3^  Upon  the  basis  of  numerous  quantita- 
tive determinations  of  the  blood  flow  in  the  hepatic  artery,  it  has  been 
found  by  this  investigator  that  the  speed  of  flow  is  300-350  mm.  in  a 
second.  This  value  is  in  close  agreement  with  similar  calculations  of 
the  velocity  of  the  blood  flow  in  other  systemic  arteries.  The  portal 
blood  stream,  on  the  other  hand,  progresses  with  a  speed  of  only  60 
to  80  mm.  per  second. 

In  the  course  of  the  experiments  just  cited  it  has  been  found  that 
the  pressure  in  the  different  tributaries  of  the  portal  vein  amounts  to 
about  10-14  mm.  Hg  and  at  the  hilus  of  the  liver  to  8-9  mm.  Hg. 
The  latter  value,  therefore,  indicates  the  pressure  under  which  the 
cells  of  the  liver  acini  secrete  the  bile  which  is  then  transferred  into  the 
biliary  spaces  and  capillaries  in  which  the  resistance  is  practically  zero. 
Moreover,  as  the  pressure  in  the  inferior  vena  cava  in  the  vicinity 
of  the  hepatic  vein  is  close  to  zero,  it  will  be  seen  that  the  resist- 
ance which  the  portal  blood  must  overcome  in  its  passage  through  the 
liver,  is  very  shght  in  comparison  with  the  resistance  offered  to  the 
blood  of  the  hepatic  artery.  Clearly,  as  the  latter  arrives  at  this 
organ  under  a  pressure  only  shghtly  below  that  prevailing  in  the 
abdominal  aorta  and  leaves  it  under  the  general  venous  pressure,  the 
loss  is  considerable.     It  must  amount  to  almost  100  mm.  Hg. 

Quantitative  measurements  of  the  arterial  influx  into  the  liver, 
in  a  dog  weighing  about  15  kg.,  have  given  a  value  close  to  3  c.c.  in  a 
second.  Moreover,  as  the  portal  influx  in  the  same  period  of  time 
amounts  to  about  5  c.c,  the  total  blood  supply  of  this  organ  may  be 
estimated  in  round  numbers  at  about  7  c.c,  per  second.     If  this  value 

1  Quart.  Jour,  of  Exp.  Physiol.,  iv,  1911,  93. 

2  Ibid.,  iii,  1910,  297. 


440        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

is  compared  with  the  total  quantity  of  blood  present  in  an  animal  of 
this  kind,  it  will  be  seen  that  the  blood  completes  the  circuit  through 
the  hepatic  blood-vessels  once  in  every  three  minutes.  But,  while  the 
liver  receives  a  larger  supply  of  blood  than  any  other  structure  in  the 
body,  its  vascularity  per  unit  of  substance  is  not  so  great  as  that  of 
the  brain  or  kidney,  because  its  weight  is  very  much  greater  than  that 
of  the  organs  just  named. 

In  agreement  with  its  double  blood  supply,  the  liver  is  equipped 
with  a  vasomotor  mechanism  which  is  capable  of  influencing  the 
arterial  as  well  as  the  venous  influx.  By  stimulation  of  the  hepatic 
plexus,  as  well  as  of  single  nerves  thereof,  it  has  been  proved  by  Burton- 
Opitz^  that  these  intrahepatic  mechanisms  are  innervated  by  the 
celiac  ganglion.  It  has  also  been  established  that  the  aforesaid  plexus 
conducts  afferent  impulses  from  the  liver,  pancreas,  and  duodenum 
to  the  solar  division  of  the  sympathetic  system,  whence  they  are  trans- 
ferred to  the  vagi  and  greater  splanchnic  nerves. 

D.  THE  CEREBRAL  CIRCULATION 

The  brain  derives  its  blood  from  the  internal  carotid  and  vertebral 
arteries,  the  anastomosis  of  the  branches  of  these  two  systems  at  the 
base  of  this  organ  being  known  as  the  circle  of  Willis.  This  reservoir 
serves  to  equalize  the  flow  of  blood  to  the  various  regions  of  the  brain, 
so  that  the  obstruction  of  one  or  more  of  its  tributary  channels  cannot 
cause  a  complete  anemia  of  this  organ.  Thus,  if  one  carotid  or  one 
vertebral  is  obhterated,  an  adequate  supply  of  blood  is  nevertheless 
obtained  through  the  channels  still  left  open.  In  fact,  it  has  been 
found  that  one  vertebral  is  sufficient  to  furnish  enough  blood  to  retain 
the  brain  in  a  functional  condition.  But,  while  the  anastomosis  is 
complete  between  the  blood-vessels  situated  at  the  base  of  this  organ, 
the  distal  or  cortical  vessels  do  not  communicate  very  freely  with  one 
another;  indeed,  several  of  them  are  terminal  in  their  character. 

The  cerebral  veins,  are  classified  in  the  same  way,  namely  as 
central  or  ganghonic  and  as  distal  or  cortical.  They  do  not,  however, 
descend  in  the  path  of  the  ascending  arteries,  but  pursue  in  most  cases 
an  independent  course;  in  fact,  some  of  them  even  ascend  with  the 
arteries.  Besides,  the  blood  stream  in  the  smaller  veins  is  frequently 
opposite  in  direction  to  that  in  the  larger  collecting  channel,  so  that 
a  certain  impediment  of  the  flow  is  produced  at  their  points  of  con- 
fluency.  That  this  condition  is  physiological  is  evinced  by  the  fact 
that  the  lumen  of  the  chief  sinus  is  frequently  rendered  uneven  by 
trabeculae  and  that  the  orifices  of  its  tributaries  are  guarded  by  valves. 
Some  sections  of  these  collecting  tubes  may  actually  be  placed  in  an 
ascending  position  by  moving  the  head. 

The  venous  sinuses  of  the  cranial  cavity  of  which  there  are  eighteen, 
are  tubular  blood  spaces  lined  with  endothelium  and  situated  between 

1  Quart.  Jour,  of  Exp.  Physiol.,  xi,  1913,  57. 


THK    CIRCULATION    THROUCH    SPECIAL    ORGANS  441 

the  porios((';il  and  in(Miin(>;oal  layers  of  I  ho  dura  mater.  In  many  places 
their  chaniu'i  is  hollowed  out  in  the  l)on(>,  their  patency  bein}^  assured 
in  addition  by  numerous  delicate  threads  of  dura  mater  fastened  to 
their  external  surface.  In  accordance  with  their  location,  these 
sinuses  collect  the  blood  not  only  from  the  cortical  and  KMnslioni^' 
veins  of  the  cerebrum,  but  also  from  the  envelopinjii;  membranes  and 
the  bones.  Moreover,  those  situated  at  the  base  receive  at  least  a 
part  of  the  blood  of  the  orbital  cavities  and  the  eyeballs. 

Intracranial  Pressure. — As  has  been  stated  above,  the  cranial 
cavity  forms  a  natural  plethysmograph  for  the  brain.  If  a  cannula 
is  insertetl  in  a  trephine^  opening  and  is  connected  with  a  recordinc; 
tambour,  two  types  of  oscillations  will  be  registered,  the  smaller  ones 
being  caused  by  the  action  of  the  heart  and  the  larger  ones  by  the  res- 
piratory movements.  They  may  be  rendered  more  conspicuous  by 
incising  the  dura,  because  this  membrane  places  a  certain  resistance 
in  the  path  of  the  expanding  brain.  In  infants,  these  pulsations 
may  be  observed  in  the  region  of  the  fontanelles,  and  in  adult  persons 
through  accidental  defects  in  the  skull.  ^  The  question,  whether  the 
cerebral  blood-vessels  are  also  expanded  when  the  skull  plates  are 
intact,  has  been  answered  positively  by  Bonders^  and  Schultze^  who 
have  observed  the  brain  through  a  piece  of  glass  firmly  fixed  and  sealed 
in  a  trephine  opening.  It  seems  that  an  interchange  of  pressure  is 
stiU  possible  in  spite  of  the  fact  that  the  brain  is  situated,  so  to  speak, 
in  a  compartment  possessing  perfectly  rigid  walls.  Under  normal 
conditions,  the  place  of  least  resistance  is  the  occipitoatlantal  mem- 
brane, but  a  shght  interchange  of  pressure  may  also  be  effected  through 
the   carotid   foramina  and  the  points  of  exit  of  the  cranial  nerves. 

At  all  events,  it  must  be  evident  that  the  brain  cannot  undergo 
more  than  a  very  limited  alteration  in  its  volume.  In  the  dog,  for 
example,  an  expansion  of  only  2  to  3  c.c.  is  possible.  A  greater  in- 
crease is  invariably  associated  with  a  rise  in  the  intracranial  pressure 
and  a  compression  of  the  cerebral  veins.  The  interchange  of  pressure, 
made  necessary  by  such  slight  volumetric  variations  as  are  produced  by 
the  systoHc  movernents  of  the  heart,  is  easily  effected  by  an  encroach- 
ment upon  the  venous  blood  current.  Thus,  we  actually  find  that  the 
distal  venous  channels  pulsate  synchronously  with  the  arteries. 
Greater  expansions  of  the  brain  are  made  possible  by  a  displacement 
of  the  cerebrospinal  fluid.  A  certain  yielding  is  also  had  at  the  fora- 
mina intervertebralia,  where  the  loose  tissue  is  pressed  outward  when- 
ever the  cerebral  fluid  is  subjected  to  an  undue  pressure.  The  tissue 
may  also  be  made  to  give  way  slightly  at  the  other  cranial  orifices. 
In  the  second  place,  we  may  obtain  an  actual  transfer  of  the  cerebral 
fluid  into  the  lymph  spaces  of  the  cord  or  into  the  l3Tiiphatic  channels 
of  the  neck,  orbital  cavity,  internal  ear,  and  cranial  nerves.     Further- 

1  For  historical  data  see  Hill,  The  Cerebral  Circulation,  London,  1896. 

^  Onderzoekingen  ged.  in  het  phys.  Lab.  d.  Utrechtsche  Hoogeschool,  1850. 

3  Med.  Zeitschr.,  St.  Petersburg,  1866. 


442        THE    NERVOUS    REGULATION    OF    THE    BLOOD-VESSELS 

more,  the  connection  between  the  lymphatic  spaces  of  the  cerebrum 
and  the  veins  is  sufficiently  free  to  allow  an  escape  of  this  liquid  when- 
ever the  intracranial  pressure  suffers  a  more  marked  and  lasting 
increase. 

Under  normal  conditions,  the  pressure  of  the  cerebral  fluid  pre- 
serves a  direct  relationship  to  the  pressure  of  the  brain,  but  only  within 
certain  limits.  Thus,  while  a  certain  compensation  is  possible,  its 
range  is  limited.  For  this  reason,  a  decided  increase  in  the  intracranial 
pressure  must  invariably  be  followed  by  a  rise  in  the  venous  pressure 
in  consequence  of  the  compression  of  the  veins.  This  change  in  turn 
leads  to  a  rise  in  the  arterial  pressure,  because  the  influx  of  the  arterial 
blood  is  thereby  retarded.  In  the  same  way,  a  marked  increase  in 
the  venous  pressure,  or  in  the  general  cerebral  blood  pressure,  mast 
be  followed  by  an  elevation  of  the  intracranial  pressure,  because  the 
spaces  containing  the  cerebral  fluid,  are  thereby  compressed  while  the 
escape  of  the  latter  into  the  veins  is  made  impossible.  Conditions 
of  this  kind  may  be  produced  without  much  difficulty  by  various 
experimental  procedures.  They  are  also  associated  with  different 
pathological  processes  such  as  tumors,  extravasations  of  blood,  an 
excessive  production  of  cerebrospinal  hquid,  and  others.  In  all  these 
cases  the  intracranial  pressure  is  raised  beyond  the  limits  of  compen- 
sation so  that  a  compression  of  the  brain  results  which  in  turn  is  fol- 
lowed by  far  reaching  and  grave  functional  disturbances.  Hindrances 
to  the  venous  return,  or  a  greater  inrush  of  arterial  blood,  produce  the 
same  general  effects,  the  only  difference  between  them  being  that,  in 
the  latter  instance,  the  cerebral  blood  pressure  is  affected  first  and  the 
intracranial  pressure  last. 

The  intracranial  pressure  may  be  increased  by  inserting  a  trephine 
cannula  in  the  region  of  the  parietal  lobe  which  is  connected  with  a 
reservoir  containing  warmed  saline  solution.  The  dura  should  be 
incised,  because  this  membrane  is  so  tense  that  it  protects  the  men- 
inges against  any  pressure  which  may  be  produced  bj^  raising  this 
reservoir.  It  will  be  found  that  the  general  blood  pressure  rises  very 
abruptly  as  soon  as  the  intracranial  pressure  has  exceeded  that  of  the 
blood.  It  does  not  remain  at  this  high  level,  however,  because  the 
heart  soon  displays  a  decided  diastolic  tendency  and  ceases  to  beat 
altogether  if  the  compression  is  continued  for  too  long  a  time.  These 
changes  are  associated  with  an  inhibition  of  respiration.  Two  ex- 
planations have  been  offered  for  this  phenomenon.  Adamkiewicz  has 
stated  that  it  is  occasioned  by  the  mechanical  damming  back  of  the 
arterial  blood  in  front  of  the  cranial  orifices,  while  Gushing^  believes 
that  it  arises  in  consequence  of  a  reflex  vasomotor  reaction.  By  meas- 
uring the  blood  flow  through  the  carotid  artery  with  the  help  of  a 
stromuhr,   Burton-Opitz  and   Edwards ^  have  shown   that  the  brain 

1  Am.  Jour,  of  Med.  Sciences,  1902  and  1903;  also  see:  Eyster,  Burrows  and 
Essick,  Jour.  Exp.  Med.,  xi,  1909,  489. 
-  Wiener  klin.  Wochenschr.,  1916. 


THE    CIRCULATION   THROUGH    SPECIAL    ORGANS  443 

nctually  recoivcs  nunc  bkxxl  durinfi;  this  period  of  height oncd  arterial 
blood  pressure,  and  heiu'(>,  it  must  lie  concluded  that  this  reaction  is 
of  nervous  origin.  It  seems  that  the  increased  intracranial  pressure 
influences  the  cerebral  centers  directly  and  gives  rise  to  a  general  reflex 
vasoconstriction  which  l^ecomes  associated  later  on  with  an  inhibition 
of  the  cardiac  and  respirator}'  activities.  It  might  be  mentioned  that 
the  procedure  just  described  may  be  used  to  imitate  the  chain  of 
symptoms  generally  associated  with  certain  lesions  of  the  brain  and 
fractures  of  the  skull. 

The  Regulation  of  the  Cerebral  Blood  Supply. — It  has  always  been 
held  that  the  vascularity  of  the  brain  is  determined  exclusively  by 
indirect  factors,  such  as  vasomotor  reactions  in  other  parts  of  the  body 
and  gravity.  At  the  present  time,  however,  when  the  existence  of 
vasomotor  nerves  to  the  cerebral  blood-vessels  can  no  longer  be  doubted, 
this  purely  mechanical  conception  must  be  modified  somewhat  to 
conform  to  actual  conditions.  Quite  naturally,  the  extracranial 
factors  just  mentioned  cannot  be  disregarded  entirely,  because  it  seems 
certain  that  they  are  capable  at  times  of  exerting  an  influence  which 
is  not  inferior  to  that  of  the  intracranial  vasomotors.  Thus,  it  may  be 
stated  that  the  vascularity  of  the  cerebrum  and  neighboring  structures 
is  controlled  in  a  direct  and  an  indirect  way,  first  by  the  vasomotor 
changes  inside  the  cranial  cavity  and  secondly,  by  vasomotor  and 
other  changes  in  more  remote  parts  of  the  body. 

This  conclusion,  however,  need  not  defer  us  from  briefly  discussing 
the  older  view  of  Roy  and  Sherrington,  which  contends  that  the  vas- 
cularity of  the  brain  is  controlled  solely  in  an  indirect  way  by  vaso- 
motor reactions  occurring  in  other  parts  of  the  body.  The  claim  is 
made  that  two  circuits  are  chiefly  concerned  in  this  interchange, 
namely,  the  portal  and  the  cutaneous.  It  is  readily  conceivable  that 
a  dilatation  occurring  in  one  or  both  of  these  vascular  areas  must  lead 
to  a  withdrawal  of  a  certain  quantity  of  blood  from  the  cerebral  blood- 
vessels. Contrariwise,  it  may  be  inferred  that  a  constriction  in  either 
region  must  force  a  certain  quantity  of  blood  into  the  cerebral  circuits. 
In  substantiation  of  this  view,  Mosso^  has  shown  that  a  constric- 
tion of  the  blood-vessels  of  the  legs  is  always  associated  with  an  in- 
crease in  the  volume  of  the  brain.  These  observations  were  made 
upon  men  with  trephine  openings  in  the  skull,  their  limbs  having  been 
enclosed  in  a  plethysmograph.  Quite  similarly,  it  has  been  observed 
by  this  author  that  the  volume  of  the  brain  is  diminished  during  sleep, 
while  that  of  the  limbs  is  increased.  A  constriction  of  the  blood-vessels 
of  the  posterior  extremities  takes  place  whenever  the  mental  activity 
is  heightened  and  especially  during  emotional  states.  We  have  seen 
above  that  the  portal  organs  require  an  increased  amount  of  blood 
during  digestion  and  that  this  extra  supply  of  blood  can  only  be 
obtained  by  withdrawing  it  from  other  parts  of  the  body,  inclusive 
of  the  cerebrum.     Concurrently,  it  may  be  gathered  that  the  cerebrum 

'  Mosso,  Ueber  den  Kreislauf  des  Blutes  im  mensch.  Gehim,  Leipzig,  1881. 


444        THE    XERVOUS.  REGULATION    OF    THE    BLOOD-VESSELS 

necessitates  the  transfer  of  a  certain  quantitj'  of  blood  from  the  portal 
organs  and  the  cutaneous  tissues,  whenever  it  is  called  upon  to  do 
extra  work.  At  all  events,  it  is  certain  that  these  systems  bear  a 
reciprocal  relation  to  one  another,  so  that,  for  example,  the  processes 
of  digestion  and  mental  activity  should  never  be  closely  associated. 

Changes  in  the  blood  supph^  of  the  brain  ma}^  also  be  effected  in 
an  indirect  way  by  various  sensory  impressions  derived  from  the  skin 
and  subcutaneous  tissues.  Thus,  the  immersion  of  the  body  in 
moderately  cold  or  warm  water,  or  its  exposure  to  cold  or  warm  air, 
produces,  on  the  one  hand,  a  vasoconstriction  and,  on  the  other,  a 
vasorelaxation.  In  the  former  case,  the  blood  flow  through  the  cere- 
brum is  augmented  and,  in  the  latter,  diminished.  These  changes  are 
generally  associated  either  with  a  greater  or  a  lesser  mental  and  bodily 
alertness.  Account  should  also  be  taken  of  the  fact  that  these  vaso- 
motor reactions  are  usually  accompanied  by  changes  in  the  energy 
of  the  heart  and  in  the  frequency  and  amplitude  of  the  respiratory 
movements. 


PART  IV 
RESPIRATION,  VOICE  AND  SPEECH 

SECTION  XII 
RESPIRATION 


CHAPTER  XXXVI 


THE   STRUCTURE  AND  FUNCTION  OF  THE  ELEMENTARY 

LUNG 

Introduction. — In  its  widest  sense  the  term  respiration  is  applied 
to  the  interchange  of  the  gases  between  hving  substance  and  the 
medium  in  which  it  is  contained.  This  is  true  of  animals  as  well  as  of 
plants,  and  since  by  far  the  greatest  number  of  protoplasmic  entities 
take  up  oxygen  and  give  off  carbon  dioxid,  respiration  is  practically 
restricted  to  the  acquisition  of  the' former  gas  and  the  discharge  of 
the  latter.  Oxygen  is  also  taken  into  the  body  in  other  ways,  for 
example,  as  a  constituent  of  the  food,  but  it  is  practically  impossible 
for  the  cells  to  make  use  of  it  in  this  form.  This  implies  that  the  cells 
do  not  possess  the  power  of  separating  it  from  its  combinations  and 
hence,  it  is  evident  that  this  gas  must  be  presented  to  them  in  an  easily 
assimilated  form,  namely,  as  "respiratory  oxygen." 

It  is  commonly  held  that  animals  inhale  oxygen  and  exhale  carbon 
dioxid,  while  plants  inhale  carbon  dioxid  and  exhale  oxygen.  In  this 
way,  it  is  assumed,  a  continuous  equilibrium  of  these  gases  is  had  for 
aU  time  to  come.  As  a  matter  of  fact,  however,  plants  possess  the 
same  respiratory  interchange  as  animals,  oxygen  being  inspired  by 
them  and  carbon  dioxid  expired.  Nevertheless,  it  is  true  that  plants, 
when  exposed  to  sunlight,  liberate  oxygen,  but  this  excess  of  the  gas 
does  not  find  its  origin  in  a  respiratory  activity  but  in  an  increased 
metabohsm  which  is  associated  with  the  assimilation  of  the  starches. 

If  we  regard  the  bacteria  as  members  of  the  animal  kingdom, 
a  classification  which  is  not  at  all  uncommon  at  the  present  time, 
it  may  be  said  that  animals  are  either  aerobic  or  anaerobic.  This 
designation  is  intended  to  convey  the  idea  that  some  of  them  thrive 

445 


446  RESPIRATION 

only  in  a  medium  containing  oxygen,  while  others,  for  example,  the 
bacillus  of  tetanus  and  the  bacillus  of  anthrax,  flourish  only  when  this 
gas  is  absent.  It  need  scarcely  be  emphasized  that  by  far  the  greatest 
number  of  organisms  are  aerobic,  i.e.,  they  take  in  oxygen  and  give 
off  carbon  dioxid. 

Diffusion  Pressure. — In  the  same  way  as  the  air  moves  from  an  area 
of  high  pressure  to  an  area  of  low  pressure,  so  do  the  individual  gases 
constituting  a  mixture,  move  from  places  of  high  to  places  of  low 
pressure.  The  driving  force  responsible  for  this  movement  of  diffusion^ 
is  furnished  by  the  partial  pressures  of  these  gases.  The  atmospheric 
air  rests  upon  us  with  a  certain  pressure  which  differs  somewhat  with 
the  temperature,  altitude,  and  other  conditions.  For  this  reason,  it 
is  necessary  to  have  a  fixed  standard  which  is  called  an  atmosphere. 
This  pressure  is  capable  of  supporting  a  column  of  mercury  760  mm. 
in  height  at  latitude  45°  and  at  sea-level,  when  the  temperature  of  the 
mercury  is  0°  C.  But  as  air  is  composed  of  several  gases,  the  total 
pressure  of  760  mm.  Hg  is  equal  to  the  sum  of  the  separate  pressures 
of  its  constituents.  Inasmuch  as  the  pressure  exerted  by  each  gas  in 
a  mixture  is  known  as  the  partial  pressure  of  that  gas,  the  pressure  of 
the  air  is  really  the  product  of  the  different  partial  pressures  of  its 
constituents. 

Dry  atmospheric  air  shows  the  following  composition: 

Oxygen 20 .  94  per  cent. 

Nitrogen 78 .  40  per  cent. 

Argon,  krypton,  neon 0.63  per  cent. 

Carbon  dioxid 0 .  03  per  cent. 

As  the  partial  pressure  exerted  by  a  certain  gas  is  proportional  to  the 

quantity  of  this  gas  present  in  the  mixture,  it  can  readily  be  seen  that 

21 
the  partial  pressure  of  the  oxygen  equals  in  round  numbers  r^  X 

79 
760  -  159.6  mm.  Hg,   and  that  of  the  nitrogen  -—  X  760  =  600.4 

mm.  Hg.  Carbon  dioxid  exerts  practically  no  pressure  at  all  in  per- 
fectly fresh  air. 

Diffusion. — In  the  lowest  forms  the  interchanges  of  the  gases  is 
effected  by  simple  diffusion.  The  medium,  whether  it  be  water  or  air, 
contains  a  certain  normal  quantity  of  oxygen.  It  is  held  here  under  a 
definite  partial  pressure.  Inside  the  organism,  on  the  other  hand,  the 
partial  pressure  of  this  gas  is  much  less,  because  it  is  constantly  used 
up  during  the  processes  of  oxidation.  On  this  account,  it  is  present 
here  in  smaller  amounts  than  in  the  medium.  Obviously,  therefore, 
the  molecules  of  oxygen  must  move  in  a  steady  stream  from  without  to 
within  directly  through  the  enveloping  membrane.  The  latter,  quite 
naturally,  offers  a  slight  resistance  to  the  diffusing  particles,  but  the 
difference  in  the  partial  pressures  is  so  great  that  this  movement  as  a 
whole  is  not  noticeably  hindered.     Quite  similarly,  the  fact  that  carbon 


THE  STRUCTURE  AND  FUNCTION  OF  THE  ELEMENTARY  LUNG   447 

dioxid  is  constantly  liberated  during  the  oxidations  proves  that  its 
partial  pressure  is  higher  inside  the  organism  than  in  the  medium,  and 
hence,  the  molecules  of  this  gas  must  move  outward,  i.e.,  in  a  direction 
opposite  to  that  of  the  particles  of  oxj'gen.  Brief  mention  should  also 
be  made  of  the  fact  that  nitrogen  is  a  functionally  inert  gas,  serving 
merely  as  the  medium  in  which  the  diffusion  of  the  other  two  gases 
takes  place.  The  function  of  argon,  krypton  and  neon  is  not  under- 
stood as  yet,  but  it  seems  that  thej''  are  of  no  importance  in  respiration. 

With  the  gi'adually  increasing  size  and  complexity  of  the  organisms 
this  method  of  interchanging  the  gases  becomes  wholly  insufficient, 
because  the  diffusion-pressures  are  not  high  enough  to  drive  the  oxygen 
directly  into  the  innermost  recesses  of  a  multicellular  body.  In- 
vaginations make  their  appearance  which  finally  take  the  form  of 
small  pouches  suspended  in  the  body  cavity  and  communicating  with 
the  outside  through  small  openings.  This  is  the  beginning  of  the 
lung,  a  specialized  organ  set  aside  for  the  purpose  of  bringing  the  air 
into  close  relation  even  with  those  cellular  units  of  the  body  which 
under  ordinary  conditions  could  not  be  reached  by  direct  diffusion. 
This  end  is  then  attained  in  an  indirect  manner  with  the  help  of  the 
bod}'  fluids.  To  begin  with,  an  interchange  of  the  gases  takes  place 
in  the  lungs,  where  the  atmospheric  air  is  brought  into  relation  with 
the  blood.  This  process  is  known  as  external  respiration.  The  freshly 
aerated  blood  is  then  directed  to  the  different  parts  of  the  body,  where 
it  enters  into  a  vivid  interchange  with  the  tissues  through  the  inter- 
vention of  the  IjTnph.  This  process  is  designated  as  internal  respira- 
tion. In  all  the  higher  animals,  therefore,  two  centers  for  the  diffusion 
of  the  gases  are  in  existence,  namely,  one  in  the  lungs  and  one  in  the 
tissues. 

The  Elementary  Lung. — In  its  most  elementary  form  the  lung 
consists  of  a  pouch-like  invagination  of  the  body-sm'face,  containing 
air  from  which  oxygen  is  constantly  abstracted,  while  carbon  dioxid 
is  passed  into  it.  But  if  this  air  were  perfectly  stationary,  an  equaliza- 
tion of  the  partial  pressures  would  soon  result,  which  in  turn  would 
lead  to  a  cessation  of  the  cUffusion.  Obviously,  therefore,  it  is  im- 
perative that  the  original  partial  pressures  be  maintained  and  this 
end  can  only  be  accomplished  by  frequently  renewing  the  air  in  this 
pouch.  If  this  is  done  at  regular  intervals,  as  the  metabolism  of  the 
body  may  demand,  the  diffusion  will  continue  at  its  normal  height 
dm'ing  the  entire  hfe  of  the  animal. 

The  question  may  now  be  asked,  how  is  this  renewal  of  the  air 
effected?  Inasmuch  as  the  lung  is  connected  with  the  outside  by 
means  of  a  relatively  long  and  narrow  tube,  its  contents  are  well  pro- 
tected against  all  movements  of  the  atmospheric  air.  Consequenth', 
the  intake  as  well  as  the  outgo  of  the  air  must  be  accomplished  by  a 
definite  activity  on  the  part  of  the  body,  in  which,  however,  the  lung 
plays  only  a  passive  part.  The  lung  as  such  does  not  possess  the  power 
of  increasing  or  decreasing  its  size,  and  hence,  is  quite  unable  to  pro- 


448 


RESPIRATION 


duce  an  inflow  and  outflow  of  air.  Instead,  it  is  to  be  clearly  under- 
stood that  the  size  and  capacity  of  this  organ  are  varied  by  an  outside 
force  which  is  applied  to  its  entire  external  surface.  This  force  is  de- 
pendent upon  the  activity  of  certain  muscles,  classified  as  respiratory 
muscles,  the  sole  function  of  which  is  to  produce  an  enlargement  of  the 
thorax  and,  in  an  indirect  way,  also  of  the  lung.  Consequently,  the 
expansion  of  this  organ  is  a  passive  phenomenon  as  far  as  the  lung  is 
concerned,  but  active  as  far  as  the  muscles  are  concerned.  This  phase 
is  soon  followed  by  a  decrease  in  the  size  of  this  particular  part  of 
the  body  and  a  decrease  in  the  size  of  the  lung.  The  former  period  is 
known  as  inspiration  and  the  latter  as  expiration. 

The  principle  involved  in  this  process  is  well  illustrated  by  the 
behavior  of  the  air-sacs  of  the  insects.  In  these  animals  we  find  a 
branched  system  of  tubes  which  communicate  through  narrow  orifices, 

known  as  stigmse,  with  small 
saccules  suspended  in  the  body 
cavity.  On  observing  an  insect 
it  will  be  seen  that  the  volume 
of  its  trunk  is  rapidly  changed 
from  moment  to  moment.  The 
walls  of  its  body  are  moved  out- 
ward by  muscular  force,  the  air- 
sacs  are  expanded  and  air  rushes 
through  the  stigmse  into  their 
interior.  At  this  time,  therefore, 
the  pressure  within  is  lower  than 
without.  Toward  the  end  of  in- 
spiration an  equilibrium  is  slowly 
established  which  causes  a  cessa- 
tion of  the  influx  of  air.  The 
expiratory  movement  now  sets  in.  The  body  wall  moves  into  its 
former  position  largely  by  recoil  with  the  result  that  the  air  in  the 
saccular  spaces  is  subjected  to  a  pressure  higher  than  that  of  the 
atmosphere.  The  air  now  escapes  through  the  stigmse  until  an  equali- 
zation of  the  pressures  has  again  been  attained.  This  alternate  ex- 
pansion and  compression  of  these  air-spaces  enables  them  to  obtain  a 
constant  supply  of  fresh  air  by  means  of  which  the  partial  pressures 
and  the  diffusion  of  the  gases  may  be  kept  up  indefinitely. 

Special  Respiratory  Organs. — Animals  may  be  divided  into  two 
classes,  namely,  into  those  living  in  atmospheric  air  and  those  living 
in  water.  Accordingly,  two  types  of  respiratory  organs  have  been  de- 
veloped, namely,  the  lungs  and  the  gills,  the  latter  being  the  phylo- 
genetically  older  mechanism.  Moreover,  those  anmials  which  spend 
their  life  in  part  in  the  former  medium  and  in  part  in  the  latter,  are 
in  possession  of  lungs  as  well  as  gills.  It  is  true,  however,  that  these 
organs  are  generally  not  functional  at  the  same  time,  because  the  change 
of  an  aquatic  into  a  terrestrial  animal  is  usually  associated  with  a 
gradual  atrophy  of  the  gills. 


Fig.  227. — Diagr.\m  of  an  Elementary 
Lung. 
S,  stigma;  O,  oxygen  diffusing  from  air  of 
saccule  into  tissue  fluids;  COt,  diffusing  in  re- 
verse direction. 


THE  STBUCTURE  AND  FUNCTION  OF  THE  ELEMENTARY  LUNG      449 

In  principle  the  structure  of  the  gills  is  the  same  as  that  of  the  lungs. 
In  both  cases  the  blood  is  brought  into  almost  direct  contact  with  the 
medium,  remaining  separated  from  it  only  by  a  layer  of  flat  endothe- 
lial cells.     Hence,  the  gills  may  be  likened  to  a  lung,  which,  so  to 


Fig.  228. — Diagi{.\m  Illustrating  the  Function  of  the  Gills. 
TT,  the  water  is  driven  across  the  surfaces  of  the  gill-plates,  whence  O  diffuses  into  the 
gill  capillaries  and  CO2  out  of  them. 

speak,  has  been  turned  inside  out  (Fig.  228).  Naturally,  the  size  of 
the  respiratory  surface  of  this  organ  differs  greatly  in  accordance  with 
the  metabolism  of  the  different  animals.  The  individual  plates 
become  more  numerous  and  frequently  extend  as  fringed  folds  far  out 


Fig.  229. — Diagram  Illustrating  the  Flow  of  the  Water  Through  the  Mouth 
Cavity  of  A  Bony  Fish.  (After  Dahlgren.) 
A,  inspiration;  B,  expiration;  M,  cavity  of  the  mouth;  D,  esophagus;  G,  gills; 
MV,  maxillary  valve;  BV,  bronchostegal  valve;  OP,  operculum  moves  outward  on 
inspiration,  opening  MV  and  closing  BV.  On  expiration  operculum  moves  inward, 
closing  first  valve  and  opening  second  valve. 

into  the  water.     These  gill-plates  are   supplied  with   venous    blood 
which  after  its  oxygenation  is  returned  into  the  dorsal  aorta. 

In  illustration  of  the  method  by  means  of  which  the  individual 
plates  are  constantly  supplied  with  fresh  water,  we  might  briefly 
consider  the  respiratory  mechanism  in  the  teleosts  (Fig.  229).     An 

29 


450  RESPIRATION 

expansion  of  the  oral  cavity  M  is  efifected  during  inspiration  by  the 
raising  of  the  opercular  apparatus,  OP.  The  branchiostegal  mem- 
brane BV  moves  inward  at  this  time  closing  the  gill  passages,  while 
the  membranous  fold  which  projects  downward  from  the  roof  of  the 
mouth  in  the  maxillary  region  and  meets  a  similar  partition  from  the 
floor  of  the  mouth  in  the  area  of  the  mandible,  moves  inward  and  per- 
mits the  water  to  enter  this  cavity,  MV.  During  the  succeeding  ex- 
piration the  contraction  of  the  opercular  apparatus  increases  the 
intraoral  pressure  and  in  turn  closes  the  aforesaid  mandiVjulomaxillary 
valve,  but  opens  the  branchiostegal  valve.  Ob\nously,  therefore, 
the  cavity  of  the  mouth  plays  the  part  of  a  force  pump,  the  flow  of 
the  water  through  it  being  determined  by  the  position  of  these  valves. 

The  sinm-hladder  or  air-bladder  of  the  fishes  possesses  the  same 
origin  as  the  lungs.  It  arises  from  an  outgrowth  of  the  forepart  of 
the  alimentary  tract,  but  becomes  speciaUzed  in  most  of  these  animals 
to  ser\'e  mereh'  as  a  hydrostatic  organ.  Its  duct,  known  as  the  ductus 
pneumaticus,  is  entirely  obliterated,  and  hence,  it  is  evident  that  the 
gas  contained  in  it  must  pass  directly  through  the  cells  lining  its  wall. 
Simple  diffusion  iviWry  explains  this  process,  but  it  must  also  be  taken 
into  account  that  its  wall  contains  sometimes  small  tubular  glands 
which  appear  to  be  there  for  the  purpose  of  actively  secreting  a  gas, 
presumably  oxj^gen.  In  some  fishes,  however,  the  duct  remains  open 
so  that  the  swim-bladder  may  also  act  as  an  accesson,''  respiratory 
organ. 

In  some  animals,  the  interchange  of  the  gases  is  effected  icith  the  help 
of  the  intestinal  canal.  A  certain  quantity  of  air  is  swallowed  which 
later  on  escapes  through  the  anus  much  poorer  in  oxA'gen  ('12  per  cent.) 
but  richer  in  carbon  dioxid  (0.8  per  cent.j.  In  warm-blooded  animals, 
intestinal  respiration  plaj-s  only  a  very  insignificant  role.  The  oxygen 
swallowed  with  the  food  is  absorbed,  but  only  very  slight  amounts  of 
carbon  dioxid  diffuse  into  the  intestinal  contents.  Quite  similarly, 
hydrogen  and  other  gases  which  are  formed  in  the  course  of  digestion 
may  pass  into  the  blood  to  be  subsequently  discharged  in  the  expiratory 
air. 

Of  much  greater  general  importance  is  the  respiratory  interchange 
through  the  skin.  In  the  lower  tj-pes  of  worms  and  arthropods,  the 
deeper  layer  of  the  integument  embraces  numerous  networks  of  capil- 
laries which  play  the  part  of  gills  as  the  sole  means  by  which  these 
animals  are  enabled  to  effect  a  proper  interchange  of  the  gases.  Am- 
phibia are  also  much  dependent  upon  the  skin  as  an  accessory  organ 
of  respiration.  In  man  the  integimient  is  rather  impermeable,  but 
Schierbeck^  states  that  the  carbon  dioxid  discharged  in  this  way  may 
amount  to  9  grams  in  24  hours  or  to  less  than  1.0  per  cent,  of  the  total 
output.  This  quantity  may  be  considerably  increased  by  sweating 
or  by  raising  the  temperature  of  the  surrounding  air.     The  oxj^gen 

1  Archiv  fiir  Anat.  und  Physiol.,  1893,  116. 


THE  STRUCTURE  AND  FUNCTION  OF  THE  ELEMENTARY  LUNG       451 


intake  through  tho  skin  is  much  loss  than  the  discharge  of  carbon 
dioxid. 

In  this  connection  mention  should  also  l)e  made  of  the  fact  that 
the  lungs  of  birds  are  beset  with  many  appendages,  or  air-sacs,  which 
communicate  with  the  bronchi  by  special  tubules  and  frequently 
extend  into  the  bones,  or  for  some  distance  between  the  muscles  and 
underneath  the  skin.  These  air-sacs  must  be  regarded  as  integral 
parts  of  the  respiratory  apparatus,  although  they  tend  to  render  the 
entire  body  more  buoyant.  The  metabolism  of  birds  is  very  intense 
and  subject  to  considerable  fluctuations.  Thus,  this  additional  respira- 
tory surface  may  be  called  upon  at  any  time  to 
effect  a  more  intense  and  rapid  interchange  of 
the  gases  without  necessitating  an  undue  expan- 
sion of  the  lung  tissue  itself. 

The  interchange  of  the  gases  in  the  placenta 
of  the  mammals  is  responsible  for  the  difference 
in  the  character  of  the  blood  of  the  umbilical 
artery  and  vein.  As  the  blood  of  the  latter 
vessel  contains  more  oxygen  and  less  carbon 
dioxid  than  that  of  the  former,  it  must  be  evi- 
dent that  this  organ  is  the  seat  of  diffusion  pro- 
cesses between  the  body  fluids  of  the  embyro 
and  mother. 

The  Complex  Lung. — To  begin  with,  the  lung 
consists  of  a  single  sac  which  possesses  no  divid- 
ing septa  and  extends  in  many  cases  through 
the  entire  length  of  the  body  cavity.  In  the 
amphibians  the  organ  becomes  paired,  consist- 
ing of  two  elliptical  pouches  of  about  equal 
length  which  communicate  with  the  pharyngeal 
cavity  through  the  bronchi  and  the  trachea  (Fig. 
230).  Furthermore,  the  breathing  surface  of 
these  sacs  is  increased  enormously  by  mem- 
branous partitions  which  project  far  into  the 
lumen  of  the  main  cavity.  Thus,  a  beginning 
is  made  of  a  differentiation  of  the  lung  into  nu- 
merous smaller  compartments  which  are  com- 
monly designated  as  air-cells  or  alveoli.  While  some  of  the  reptiles 
retain  this  type  of  lung,  many  of  them  show  a  much  higher  state 
of  development  of  this  organ,  because  the  individual  alveoli  are  en- 
tirely separated  from  the  main  cavity  and  communicate  with  the 
latter  only  through  small  orifices.  In  these  we  recognize  the  be- 
ginnings of  the  bronchiolar  tubules.  With  the  increasing  alveoliza- 
tion  of  the  lung,  the  bronchi  and  bronchioles  are  really  separated 
into  an  ''extra  pulmonary"  system  of  tubes  which  are  generally  pro- 
vided with  solid  cartilaginous  rings  and  eventually  also  with  muscular 
tissue.     The  capillary  networks  which  at  first  are  restricted  to  the  very 


Fig.  230.— Diagram 
Illustrating  the  Func- 
tion OF  THE  Amphibian 
Lung. 

T,  trachea;  B,  bron- 
chi; L,  lung  of  one  side; 
P,  septa  dividing  the 
main  cavity  into  smaller 
air-spaces  or  alveoli  (A). 


452 


RESPIRATION 


walls  of  tho  lungs,  ovontually  invade  the  membranous  partitions. 
As  a  result  of  this  extension,  a  much  larger  sheet  of  blood  is  brought 
into  direct  diffusion  contact  with  the  air  in  the  alveoli. 

The  mechanism  of  respiration  in  these  animals  is  very  simple.  The 
floor  of  the  mouth  is  depressed  by  muscular  activity  so  that  the  pres- 
sure within  this  cavity  falls  ])elow  that  of  tlie  outside  air.  A  certain 
quantity  of  air  then  enters  through  the  nostrils  until  an  equalization 
of  pressure  has  been  effected.  The  nostrils  are  then  closed  and  the 
glottis  opened.  The  subsequent  elevation  of  the  floor  of  the  mouth 
now  forces  the  air  into  the  lungs.  Here  it  remains  for  a  time  until  a 
part  of  it  is  allowed  to  escape  through  the  opened  glottis  and  nostrils 


Fig.  231. — Human  Respiratory  Apparatus  Showing  the  Br.\nching  of  the  Bronchi 
IN  THE  Interior  of  the  Lungs.     (Duval.) 

in  consequence  of  the  passive  recoil  of  the  parts  previously  put  under 
elastic  tension.  This  mechanism  again  illustrates  the  action  of  a 
force-pump. 

The  Mammalian  Lung.— The  lung  of  the  mammal  exhibits  several 
of  the  characteristics  of  the  reptilian  lung.  Beginning  at  the  pharyn- 
geal cavity,  the  trachea  with  its  modified  upper  portion,  known  as  the 
larynx,  passes  backward  for  a  distance  of  about  12  cm.  and  divides 
into  two  main  branches,  the  bronchi.  The  latter  subdivide  again  and 
again  until  small  terminals,  or  bronchioles,  are  obtained  which  in- 
dividually connect  with  irregular  spaces,  known  as  infimdibula.  These 
in  turn  are  made  up  of  a  number  of  minute  cellular  spaces,  or  alveoli. 


THE  STRUCTUEE  AND  FUNCTION  OF  THE  ELEMENTARY  LUNG       453 

The  sinallor  hronchiolos  aro  not  In  possession  of  a  cartilaginous  framework, 
hut  consist  merely  of  fii)rous  and  elastic  tissue  and  a  scanty  layer  of  smooth  muscle 
cells.  The  larger  tul>es,  on  the  otlier  hand,  are  ecjuipped  with  rings  of  cartilage 
to  render  them  more  resistant  against  the  variations  in  pressure  to  which  they 
are  subjected  during  each  respiratory-  act.  This  entire  tract  is  lined  with  a  layer 
of  epithelium  which,  in  the  trachea,  bronchi  and  bronchioles,  Is  of  the  ciliated 
columnar  variety  and,  in  the  outer  parts  of  the  infundibulum,  cuboidal  in  shape. 
The  efTective  stroke  of  the  cilia  is  in  the  direction  of  the  mouth,  so  that  much  of 
the  foreign  material  carried  in  with  tlie  air  is  again  expelled  without  extra  efforts. 
The  specialized  respiratory  epithelium  is  restricted  to  the  alveolar  walls.  These 
are  composcfl  of  connective  tissue  containing  a  large  number  of  elastic  fibers  and 
an  external  lining  of  very  flat  and  large  cells.  The  elastic  tissue,  as  we  shall  see 
later,  is  responsible  for  the  traction  which  the  lung  constantly  exerts  upon  the  in- 
ternal surface  of  the  chest  wall. 


Fig.  232. — Diagram  Illustrating  the  Arrangement  of  the  Infundibula. 
B,  Bronchiole;  D,  infundibular  duct;  /,  infundibulum;  A,  alveolus;  S,  interinfun- 
dibular  space,  occupied  by  capillaries. 


The  blood-vessels  ramify  in  all  directions  through  the  interalveolar  walls; 
moreover,  as  the  infundibular  vesicles  are  packed  close  together,  the  blood  is 
brought  into  intimate  relation  with  the  air,  being  separated  from  it  merely  by  the 
lining  ceDs  of  the  capillaries  and  alveoli.  In  fact,  in  some  of  the  higher  animals 
(birds)  the  alveolar  walls  seem  to  be  devoid  of  lining  cells.  It  should  also  be 
remembered  that  by  far  the  largest  quantity  of  blood  furnished  by  the  pul- 
monary artery,  serves  respiratory  purposes  only.  Thus,  if  a  man  weighing  70 
kilos,  possesses  4.5  kilos  of  blood,  not  less  than  700  grams  of  this  amount  are 
contained  in  the  pvdmonary  blood-vessels.  Furthermore,  if  the  circulation-time 
in  the  lesser  circuit  is  reckoned  at  13  seconds,  it  will  readily  be  seen  that  close  to 
200  kilos  of  blood  traverse  the  lungs  in  an  hour  and  4500  kilos  in  a  day.  A  verj' 
small  portion  of  this  blood  Ls  required  for  the  nutrition  of  this  organ,  but  it  seems 
that  this  amount  is  derived  directly  from  the  aorta  by  those  arterial  branches  which 
are  distributed  to  the  bronchi,  interlobular  septa,  pleural  membranes  and  the 
trunks  of  the  blood-vessels  leaving  the  heart.     The  venous  return  from  these  parts 


454 


RESPIRATION 


is  effected  bj^  the  corresponding  veins,  but  some  of  this  blood  also  finds  its  way 
into  the  pulmonarj'  veins  by  anastomoses. 

The  diameter  of  the  alveoli  varies  between  120  and  380  fx,  their  average  diam- 
eter being  120  jx:  Inasmuch  as  from  300  to  400  milhons  of  alveoli  are  contained 
in  each  lung,  and  inasmuch  as  one  of  them  possesses  an  area  of  about  0.321  mm.^ 
the  total  respiratory  surface  must  amount  to  130  m.-  in  men  and  to  104  m.^  in 
women.  If  these  values  are  now  compared  with  the  size  of  the  bodj'-surface,  it 
will  be  seen  that  the  latter  is  100  to  125  times  smaller  than  the  respiratory  surface 
of  our  lungs.  It  must  be  evident,  however,  that  the  area  formed  by  the  pulmonary 
blood  is  somewhat  smaller  than  the  alveolar  surface,  because  the  capillaries  do 
not  occupy  the  entire  extent  of  the  alveolar  surface.  Thus,  it  has  been  estimated 
that,  if  all  the  blood  present  in  the  lungs  of  a  man,  could  be  made  to  form  a  single 
layer  measuring  10  /x  in  thickness,  it  would  cover  an  area  of  120  m.-.  These 
figures,  very  naturally,  are  only  approximately  correct  and  are  not  intended  to 
be  memorized  but  simply  to  permit  us  to  form  an  idea  regarding  the  enormous 
surface  of  blood  brought  into  relation  with  the  outside  air. 


CHAPTER  XXXVII 
THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS 

General  Topography. — The  lungs  of  the  mammal  are  contained  in 
the  cavity  of  the  thorax  which  forms  the  fore  part  of  the  general 


Fig.  233. — Illustration  to  Show  the  Position  of  the  Luxgs  in  Their  Relation  to 
THE  'Wall  of  the  Thor-uc. 


cavity  of  the  trunk.  They  are  surrounded  on  all  sides  by  relatively 
solid  walls,  made  so  by  a  copious  inlay  of  bony  laminae.  From  the 
abdominal  cavity  they  are  completely  separated  by  a  muscular  sep- 
tum, the  diaphragm,  but  communicate  with  the  pharyngeal,  nasal 


THE  IMKCHANICS  OF  THK  RESPIRATORY  MOVEMENTS  455 

and  oral  cavities  by  a  relatively  narrow  tube,  known  as  the 
trachea.  This  almost  air-ti^;ht  compartment  of  the  thorax  possesses 
a  conical  outline,  its  tip  beiu^  situated  at  the  root  of  the  neck  and  its 
liase  at  the  di:i])iiraf«;in.  Its  venti-ul  wall  is  formed  l)y  the  sternum  and 
adjoining  costal  cartilages,  its  sides  by  the  ribs,  and  its  dorsal  wall  by 
the  vertebral  column. 

The  two  lungs  occupy  almost  the  entire  thoracic  cavity,  only  its 
central  extent  being  allotted  to  the  heart  and  large  blood-vessels 
with  their  pericardial  investment.  Each  organ  is  closely  enveloped  by 
a  delicate  membrane  which  is  reflected  from  the  bronchi  and  lines 
the  entire  internal  surface  of  the  chest  wall.  Consequently,  this 
membrane  which  is  known  as  the  pleura,  consists  of  two  layers,  an 
outer  or  parietal  and  an  inner  or  visceral.  The  opposing  surfaces  of 
t  hese  layers  are  lined  with  flattened  endothelial  cells  and  are  moistened 
with  a  lymphatic  secretion  to  prevent  frictioning.  It  must  be  em- 
phasized, however,  that  the  layers  of  the  pleura  always  remain  in  close 
contact  with  one  another  and  that  an  actual  pleural  cavity  cannot  be 
present  so  long  as  the  walls  of  the  chest  remain  intact.  Urider  normal 
conditions,  therefore,  the  visceral  and  parietal  layers  of  the  pleura 
act  as  one  membrane  which  is  interposed  between  the  chest  wall  and 
the  substance  of  the  lung  to  facilitate  the  movement  coincident  with  the 
expansion  of  this  organ.  Between  the  left  and  right  pleural  sacs  is  a 
space,  known  as  the  mediastinum,  which  is  divided  into  an  anterior 
and  a  posterior  compartment  by  the  heart  with  its  pericardial  in- 
vestment. In  some  animals,  such  as  the  rabbit,  this  interpleural 
space  is  broad,  so  that  it  is  possible  to  expose  the  heart  through  the 
median  line  of  the  sternum  without  rupturing  the  pleural  sacs.  But 
a  procedure  of  this  kind  is  not  feasible  in  most  mammals,  because  the 
anterior  borders  of  the  lungs  extend  almost  to  the  median  Une  of  the 
thorax. 

THE  RESPIRATORY  CYCLE 

The  muscular  act  by  means  of  which  the  air  in  the  pulmonary 
passages  is  constantly  kept  in  a  fresh  state,  consists  in  an  alternate 
increase  and  decrease  in  the  size  and  capacity  of  the  thorax  which  in 
turn  results  in  a  corresponding  alteration  in  the  size  of  the  lungs. 
In  spite  of  their  relative  sohdity,  the  walls  of  the  chest  are  flexible  so 
that  they  may  be  moved  either  away  from  or  toward  a  common  center. 
The  former  movement  takes  place  during  inspiration  and  the  latter 
during  expiration,  and  naturally,  as  the  intrapulmonary  passage 
stands  in  communication  with  the  outside  through  the  trachea,  an 
inflow  of  atmospheric  air  must  result  during  the  expansion  of  the  lung 
and  an  outflow  during  its  subsequent  period  of  recoil.  Concurrently, 
it  may  rightly  be  inferred  that  the  outward  movement  of  the  chest 
wall  may  be  greatly  restricted  by  obstructing  the  trachea,  because  this 
would  prevent  the  inflow  of  air  and  hence,  nullify  the  volumetric  in- 
crease in  the  capacity  of  the  chest  which  in  turn  gives  rise  to  the  expan- 
sion of  the  lungs. 


456 


EESPIRATION 


The  chest  is  never  at  rest  but  is  either  in  the  position  of  inspiration  or 
expiration,  and  hence,  the  respiratory  cycle  is  one  of  constant  activity. 
Between  the  end  of  every  expiration  and  the  beginning  of  the  succeed- 
ing inspiration  the  thorax  exhibits  a  condition  of  quiescence  which  is 
sometimes  erroneously  designated  as  the  respiratory  pause.  Thus, 
it  may  be  stated  that  the  respiratory  cycle  includes  a  dynamic  and  a 
static  phase,  the  former  consisting  of  the  inspiratory  and  expiratory 
periods,  and  the  latter  of,  this  period  of  comparative  passiveness  and 
rest.  It  should  be  remembered,  however,  that  the  elasticity  of  the 
lungs  and  of  the  parts  forming  the  thoracic  walls  does  not  cease  to 
act  even  during  the  i-espiratory  interims,  when  the  muscle  tissue  is 
actually  in  a  state  of  rest.  For  this  reason,  it  may  justly  be  said  that 
a  true  pause  does  not  exist  during  life,  although  it  may  be  produced 
experimentally.  Hence,  the  term  static  should  be  used  solely  in  a 
relative  sense. 


Fig.  234. — Diagram  Illustrating  the  Course  of  the  Pleura. 
T,  trachea;  L,  lung;  H,  heart;  A,  abdominal  cavity;  C,  collapsed  lung  (the  rest  of 
this  cavity  being  filled  with  air  (pneumothorax);  V,  visceral  pleura;  P,  parietal  pleura 
reflected  from  root  of  lung  (dotted  line). 

A.    THE  STATIC  PHASE. 

At  the  end  of  expiration  the  thorax  and  the  organs  contained 
therein  maintain  for  a  very  brief  time  a  position  from  which  several 
of  the  fundamental  principles  of  respiration  may  readily  be  inferred. 
The  entire  cavity,  with  the  exception  of  the  mediastinal  space,  is 
filled  by  the  lungs  which  are  everywhere  in  immediate  contact  with 
the  internal  surface  of  the  chest  wall.  Externally,  they  are  protected 
against  the  atmospheric  pressure  by  the  relatively  solid  framework 
of  the  thorax  and  atmospheric  pressure  prevails  in  all  the  intrapul- 
monary  spaces  and  passages. 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS  457 

Collapse  of  the  Lung. — A  very  diiferent  picture  is  presented 
if  the  uir  is  permitted  to  act  upon  the  outside  surface  of  the  lung. 
This  end  can  be  attained  by  puncturing  the  pleural  cavity  in  any 
intercostal  space  or  by  forming  a  communication  between  this  cavity 
and  the  respiratory  passage.  The  former  condition  frequently  results 
in  consequence  of  gunshot  or  stab  wounds,  and  the  latter,  in  consequence 
of  perforations  through  tuberculous  lung  tissue.  The  opening  of 
the  pleural  cavity  is  immediatel}^  followed  by  the  retraction  of  the 
external  surface  of  the  corresponding  lung  from  the  internal  surface 
of  the  chest  wall,  the  intervening  space  being  filled  with  air.  This 
condition  which  is  known  as  pneumothorax,  cannot  be  remedied  as  long 
as  the  opening  in  the  pleural  cavity  remains  patent;  in  fact,  the  air 
entrapped  in  the  collapsed  organ  is  then  gradually  absorbed,  while  the 
formerly  buoyant  tissue  solidifies  and  loses  its  function  permanently. 
Obviously,  a  lung  which  has  lost  its  elasticity  does  not  collapse 
readily,  but  tends  to  preserve  its  original  volume  (emphysema). 

If  the  communication  between  the  pleural  space  and  the  outside  is 
again  closed,  the  air  in  this  cavity  is  slowly  absorbed  with  the  result 
that  the  lung  gradually  increases  in  volume  until  it  again  lies  every- 
where in  contact  with  the  chest  wall  and  can  again  be  subjected  to 
normal  degrees  of  expansion.  It  might  also  be  mentioned  that  the 
collapse  of  one  lung  need  not  necessarily  prove  fatal,  because  the  oppo- 
site organ  is  capable  of  a  certain  degree  of  hyperexpansion  which  will 
tend  to  make  up  for  the  loss  sustained  on  the  opposite  side.  In  addi- 
tion, it  is  noted  that  the  normal  organ  most  generally  acquires  a  cer- 
tain amount  of  new  tissue  which  will  enable  it  in  time  to  perform  its 
compensatory  function  in  a  more  complete  manner.  Attention  might 
also  be  called  to  the  fact  that  perforating  wounds  of  the  lung  are  not 
alwaj^s  followed  by  a  collapse  of  the  injured  organ,  because  the  weapon 
may  again  be  withdrawn  without  that  the  air  has  had  a  chance  to 
enter  the  intrapleural  space.  The  diameter  of  the  modern  bullet  is 
so  small  and  its  velocity  so  great  that  the  parts  are  scarcely  lac- 
erated and  are  still  able  to  recoil  and  to  close  the  defect  almost 
immediately. 

Another  condition  in  which  similar  conditions  prevail  is  pleurisy.  The  dry 
stage  of  this  inflammatory  reaction  having  been  passed,  a  serous  exudate  forms 
upon  the  pleural  surfaces  which  in  time  gravitates  into  the  most  dependent  portion 
of  the  iatrapleural  space  and  gradually  separates  the  visceral  from  the  parietal 
pleura.  Eventually  the  lung  is  pushed  far  away  from  the  wall  of  the  thorax 
until  its  volume  scarcely  exceeds  that  of  a  collapsed  organ.  Conditions  of  this 
kind  constitute  hydroihorax.  During  the  subsequent  period  of  absorption,  this 
exudate  is  gradually  removed  with  the  result  that  the  lung  is  slowly  drawn  toward 
the  chest  wall  until  the  pleural  cavity  is  again  converted  into  a  potential  capillary 
space.  In  this  connection  mention  might  also  be  made  of  the  fact  that  the  com- 
pression and  resultant  reduction  in  the  respiratory  capacity  of  this  lung  may  be 
relieved  by  withdrawing  the  fluid  with  the  help  of  an  aspirating  syringe. 

Intrapleural,    Intrathoracic    and   Intrapulmonic   Pressures. — The 

foregoing  conditions  have  been  discussed  somewhat  at  length,  because 


458  RESPIRATION 

they  illustrate  in  a  most  convincing  manner  the  principle  upon  which 
the  mechanics  of  respiration  are  based.  They  prove  first  of  all  that  the 
lungs  are  held  in  firm  contact  with  the  internal  surface  of  the  chest  wall 
by  a  definite  force,  the  removal  of  which  immediately  allows  the  pul- 
monary tissue  to  separate  itself  from  the  wall  of  the  thorax.  In  the 
second  place,  they  prove  in  an  unmistakable  manner  that  the  tissue 
of  the  lung  is  elastic,  and  that  it  is  constantly  held  in  a  state  of  hyper- 
distention.  On  this  account  the  wall  of  the  chest  is  always  exposed  to 
the  elastic  recoil  of  the  lungs,  the  tendency  of  which  is  to  allow  the 
stretched  interalveolar  fibers  to  regain  their  normal  length  and  shape. 
Obviously,  therefore,  these  organs  are  always  kept  in  an  expanded  state 
by  a  force  resting  upon  their  external  surface  and  not  by  a  force  acting 
upon  the  walls  of  the  respiratory  passage  from  within.  In  other 
words,  the  lungs  are  not  inflated  by  a  current  of  air  forced  in  through 
the  trachea,  but  are  expanded  from  without,  this  movement  causing 
air  to  flow  into  their  recesses.  Consequently,  excepting  the  elastic 
recoil  during  expiration,  the  lungs  do  not  actually  participate  in  an 
active  way  in  the  shifting  of  the  respiratory  air. 

The  force  which  keeps  the  lungs  in  contact  with  the  internal  sur- 
face of  the  chest  wall  is  the  pressure  prevailing  in  the  intrapleural 
space.  In  the  nature  of  things,  it  is  the  pressiu-e  which  the  elastic 
power  of  the  lungs  would  have  to  overcome  in  order  to  pull  the  pleural 
layers  apart,  but  as  the  capillary  space  between  the  latter  is  closed, 
the  recoil  of  the  pulmonary  tissue  is  much  too  sHght  to  overcome  this 
resistance.  It  follows,  therefore,  that  the  lungs  and  the  chest  wall 
must  remain  in  the  closest  possible  opposition.  Supposing,  moreover, 
that  the  pressure  in  the  passages  of  the  lung  amounts  to  one  atmos- 
phere, or  760  mm.  Hg,  the  pressure  to  which  the  heart,  great  vessels, 
and  other  structures  of  the  thoracic  cavity  are  exposed,  must  be  less 
than  this  figure,  because  the  elastic  tension  of  the  pulmonary  tissue 
constantly  opposes  and  counterbalances  the  atmospheric  pressure. 
Thus,  it  must  be  clear  that  the  pressure  prevailing  immediately  out- 
side the  surfaces  of  the  lungs,  i.e.,  in  the  intrapleural  space,  must  be 
that  of  the  atmosphere  minus  the  elastic  recoil  of  the  lung  tissue. 

In  attempting  to  measure  this  elastic  pull  of  the  pulmonary  tissue 
Bonders^  connected  the  trachea  of  a  dead  animal  with  a  mercurial 
manometer  and  permitted  the  lungs  to  collapse  by  perforating  the 
chest  wall.  Quite  naturally,  the  recoiling  lungs  placed  the  air  within 
them  under  a  certain  pressure,  a  fact  which  was  most  clearly  betrayed 
by  the  outward  movement  of  the  column  of  mercury.  It  was  found 
in  this  way  that  the  lungs  are  capable  of  counterbalancing  a  mercurial 
column  about  6  mm.  in  height  and  hence,  if  this  figure  is  subtracted 
from  760  mm.,  the  resulting  value  of  754  mm.  indicates  the  pressure 
prevailing  in  the  intrapleural  space  and  other  regions  of  the  thoracic 
cavity  outside  the  respu-atoiy  channel. 

^Zeitschr.  fiir  rat.  Med.,  iii,  287. 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS 


459 


Practically  tho  samo  result,  has  been  obtained  by  connecting;  a  mano- 
meter with  the  intrapleural  space  by  means  of  a  hollow  tube  which  is  in- 
serted through  an  intercostal  space  (Fig.  235) .  On  piercing  the  parietal 
pknu'a,  the  visceral  layer  is  pusluxl  ahead  of  the  prol)e  (P)  so  that  its  free 
end  comes  to  lie  in  a  recess  of  the  intrapleural  cavity,  and  is  directly 
exposed  to  the  elastic  recoil  of  the  lung.  In  this  particular  case,  the 
mercury  in  the  manometer  (M)  is  drawn  toward  the  chest  causing  its 
proximal  liml)  to  rise  and  its  distal  limb  to  fall  until  the  negativity 
in  the  thorax  has  been  counterbalanced  exactly.  The  manometer 
therefore,  measures,  the  traction  which  is  brought  to  bear  upon  the 
internal  surface  of  the  chest  wall  by  the  recoiling  pulmonary  tissue 
and  the  force  with  which  it  opposes  the  pressure  in  the  respiratory 


Fig.  235. — DiAGRAii    iLLrsxRATixo   the   Manner  of  Insertion  of  a   Cannula  into 

THE    InTRAPLETJRAL    SpACE. 

T,  trachea;  L,  lungs;  H,  heart;  A,  abd.  ca%dty;P,  a  probe  is  pushed  through  the  inter- 
costal space  forcing  the  lung  away  from  the  chest  wall  and  thus  creating  an  artificial 
space;  M,  the  manometer  then  indicates  the  elastic  pull  of  the  lungs;  »S,  stopcock  to 
prevent  ingress  of  air  before  manometer  is  in  place;  K,  kymograph  for  recording  the 
intrapleural  pressure. 


passage.  Hutchinson^  has  attempted  to  measure  the  elastic  force  of 
freshly  excised  human  lungs  by  distending  them  with  known  amounts 
of  air.  Upon  these  figures  Heynsins^  bases  his  conclusion  that  the 
intrapleural  pressure  during  the  static  phase  of  the  thorax  amounts  to 

—  4.0  mm.  Hg.     For  dogs  and  rabbits  the  values  of   —3.9  mm.  and 

—  2.5  mm.  Hg  respectively  have  been  found. 

It  must  be  evident  that  the  term  intrathoracic  pressure  indicates 
the  pressure  prevailing  elsewhere  in  the  thoracic  cavity  outside  the 
pulmonary  passage.     Consequently,  the  terms  intrapleural  and  intra- 

^  Hermann's  Handb.  der  Physiol.,  iv,  225 
,  2  Pfliiger's  Archiv,  xxix,  1S82,  265. 


460 


RESPIRATION 


thoracic  pressure  apply  to  one  and  the  same  phenomenon,  but  while  the 
former  has  reference  only  to  the  intrapleural  space,  the  latter  includes 
all  regions  of  the  thoracic  cavity  in  which  its  contents  are  subjected 
to  the  elastic  pull  of  the  lungs.  The  term  intrapulmonic  pressure  is 
indicative  of  the  pressure  prevailing  in  the  air  passages  of  the  lungs. 
At  the  end  of  inspiration,  as  well  as  at  the  end  of  expiration,  the  pressure 
in  the  respiratory  channels  equals  that  of  the  air  without.  No  move- 
ment of  the  air  is  possi})le  as  long  as  the  pressures  remain  equal. 

The  Cause  of  the  Negativity  of  the  Intrathoracic  Pressure. — During 
intra-uterine  life  the  lungs  are  atelectatic,  i.e.,  they  contain  no  air. 
The  walls  of  their  alveoli  and  smaller  tubules  are  in  opposition,  while 
the  larger  passages  contain  in  all  probability  a  moderate  quantity  of 
fluid  material.     Their  solidity  leads  us  to  infer  a  high  specific  gravity, 


Fig.  236. — Diagram  Illustrating  the  Origin  of  the  Intrathoracic  Pressure. 
A,  at  birth  the  lungs  contain  no  air  and  fill  the  ca\'ity  of  the  thorax  completely; 
B,  after  the  first  respiration  the  cavity  of  the  thorax  is  much  enlarged  in  size  by  the 
outward  movement  of  the  chest  walls.     Consequently,  air  is  drawn  into  the  recesses  of 
the  lung. 


a  fact  which  is  employed  as  a  basis  for  an  important  medicolegal  test. 
Thus,  the  lungs  of  a  still-born  infant  sink  when  placed  in  water,  while 
an  organ  which  has  been  expanded  is  buoyant  and  able  to  carry  not 
only  the  weight  of  its  own  tissue  but  also  that  of  the  heart  and  large 
blood-vessels.  From  this  we  may  draw  the  conclusion  that  the  lungs 
of  the  fetus  are  under  no  elastic  tension  and  fill  the  thoracic  cavity 
completely.  Consequently,  the  capacity  of  the  latter  must  equal  the 
volume  of  the  lungs,  and  hence,  it  must  be  possible  to  puncture  the 
chest  wall  without  producing  a  collapse  of  these  organs. 

At  birth,  however,  the  violent  muscular  efforts  immediately  give 
rise  to  an  outward  movement  hi  the  walls  of  the  thorax  and  an  increase 
in  the  size  of  this  cavity.  Moreover,  as  the  external  surface  of  the 
lungs  is  in  firm  opposition  with  the  chest  wall,  it  is  drawn  outward 
with  the  result  that  air  now  rushes  into  its  innermost  passages  and 
recesses.  To  begin  with,  only  a  limited  number  of  alveoli  are  rendered 
air-containing,  but  the  succeeding  movements  distend  them  in  increas- 
ing numbers  until  the  organ  as  a  whole  becomes  fully  expanded.     Most 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS  4G1 

goiierally,  sevcrul  clays  arc  required  liefore  the  infanl.iU^  lung  is  distended 
in  its  entirety.  But,  the  important  fact  to  remc^mber  is  tliat  the  ratlier 
sudden  increase  ii\  the  capacity  of  the  thoracic  cavity  occasions  tin 
equally  abrupt  increase  in  the  vohunc  of  the  lungs  which  is  made 
possible  only  by  an  influx  of  air  into  its  passages.  In  this  way,  the 
walls  of  the  different  alveoli  are  put  on  the  stretch  and  are  held  in  this 
position  throughout  the  life  of  the  individual.  At  this  very  moment 
arises  the  elastic  recoil  of  the  pulmonary  tissue,  i.e.,  the  attempt  of 
its  constituents  to  resume  their  former  length  and  shape.  Upon 
this  recoil  d(^pends  the  negative  pressure  in  the  thoracic  cavity;  and 
clearly,  as  this  difference  in  the  capacity  of  the  thorax  and  the  volume 
of  the  lungs  is  present  at  the  end  of  expiration  and  even  after  death, 
this  negativity  is  a  permanent  condition,  which  may  be  removed  only 
by  perforating  the  chest  wall.  It  is  true,  however,  that  this  negative 
pressure  is  very  slight  during  the  first  four  days  of  extra-uterine  life, 
and  amounts  to  only  —0.4  mm.  Hg  at  the  end  of  one  week.  Subse- 
quent to  this  time  a  much  greater  negativity  is  gradually  developed, 
because  the  wall  of  the  chest  now  becomes  more  resistant  and  grows 
more  rapidly  than  the  lung.  In  order  to  overcome  this  difference  the 
lungs  are  slowly  subjected  to  an  even  greater  expansion,  tending  to 
accentuate  their  elastic  tension  and  to  increase  the  negativity  of  the 
intrathoracic  pressure.  From  these  facts  it  may  also  be  gathered 
that  the  lungs  of  the  infant  are  more  thoroughly  emptied  with  each 
respiratory  act  than  those  of  the  adult. 

B.  THE  DYNAMIC  PHASE 

The  Respiratory  Movements. — The  phenomena  presented  by  the 
active  lung,  are  in  no  way  different  from  those  previously  considered. 
We  must  remember  first  of  all  that  the  lung  remains  in  firm  contact 
with  the  chest  wall,  because  its  elastic  recoil  is  not  sufficient  to  allow 
it  to  separate  the  visceral  from  the  parietal  surface  of  the  pleura  and  to 
create  a  real  intrapleural  space.  Consequently,  it  must  be  evident 
that  its  degree  of  expansion  is  wholly  determined  by  the  position  of 
the  wall  of  the  thorax.  If  the  latter  moves  outward,  the  external 
sm-face  of  the  lung  must  follow  in  the  same  direction  and  give  rise  to 
an  expansion  of  the  entire  organ.  Air  then  rushes  into  its  inner  pas- 
sages. During  the  succeeding  expiratory  phase,  the  chest  wall  moves 
inward.  The  lung  then  recoils  in  a  certain  measure  and  drives  a 
definite  quantity  of  air  to  the  outside.  Obviously,  therefore,  the  lung 
plays  the  part  of  a  passive  tissue,  the  active  factor  being  the  chest  wall. 

The  respiratory  movements  consist  of  an  alternate  outward  and 
inward  movement  of  the  wall  of  the  thorax  which  leads  first  to  an 
increase  and  then  to  a  decrease  in  the  capacity  of  this  cavity  and  a 
corresponding  change  in  the  distention  of  the  lungs.  The  former 
movement,  constituting  inspiration,  is  the  result  of  the  activity  of  the 
muscles  of  inspiration,  whereas  the  latter,  constituting  expiration,  is  a 


462 


EESPIRATION 


passive  process,  depending  mainly  upon  the  elastic  recoil  of  the  parts 
previously  put  on  the  stretch.  The  enlargement  of  the  thoracic  cavity 
is  accompUshcd  in  three  directions,  namely,  along  its  vertical,  transverse 
and  anteroposterior  planes. 

The  increase  in  the  vertical  diameter  is  effected  with  the  help  of  the 
diaphragm.  This  musculotendinous  septum  which  forms  the  dividing 
line  between  the  thoracic  and  abdominal  cavities,  arises  from  the  first 
three  or  four  lumbar  vertebrae  and  adjoining  fascia,  from  the  borders 
of  the  six  lower  ribs  and  from  the  ensiform  cartilage.  The  individual 
fibers  strive   radially  toward  a  common  center,  keeping  first  in  close 


•^ 


Fig.  237. — .Vi'i'AitAiLs  .\i<it.'UNuti>  lun  1llu»'ika'ii.\u  iHt.  Expansion'  of  the  Lung. 
N,  bell  jar;  B,  rubber  balloon;  M,  manometer.  The  rubber  membrane  closing  the 
bell  jar  is  pulled  down  in  imitation  of  the  contraction  of  the  diaphragm.  This  causes 
the  expansion  of  the  balloon  by  a  negative  pressure  resting  upon  its  surface.  The 
upward  movement  of  this  membrane  corresponds  to  expiration.  The  manometer  is 
connected  with  the  space  between  the  walls  of  the  bell  jar  and  the  balloon  (intra- 
pleural space)  and  registers  the  changes  in  pressure.     (Laulanie.) 

contact  with  the  chest  wall  but  later  on  turning  rather  abruptly  to  be 
inserted  into  the  edges  of  the  tendinous  central  area  of  this  septum. 
The  latter  generally  conforms  to  the  outline  of  the  body  and  appears 
most  frequently  in  two  segments,  a  right  and  a  left  (Fig.  239).  In 
cross-section,  therefore,  the  diaphragm  presents  a  dome-shaped  outline, 
its  convex  surface  being  turned,  into  the  thoracic  cavity.  At  the  side, 
only  the  smallest  possible  space  separates  its  upper  surface  from  the 
wall  of  the  chest  so  that  its  pai'ietal  pleura  lies  in  absolute  contact  with 
the  parietal  pleura  lining  the  inner  surface  of  the  thorax.  At  a  some- 
what higher  level,  this  capillary  space,  which  is  known  as  the  "com- 
plementary" pleural  cavity,  soon  widens  out  into  the  general  cavity 
of  the  thorax. 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS  403 

As  the  diaphragm  contracts,  its  tendinous  portion  is  pulled  down- 
ward, so  that  this  septum  as  a  whole  assumes  a  much  flatter  outUne 


Fig.  238. — Diagrammatic  Sectionsofthe  Body  in  A,  Inspiration;  and  B,  Expiration; 
Tr,  Trache.4;  St,  Sterxtm;  D,  Diaphr.a.gm;  Ab,  Abdominal  ^^■ALLS.  The  Shadixg 
Roughly  Indicates  the  Stationary  Air.  {From  Huxley's  "Lessons  in  Elementary 
Physiology,"  Macmillan  Co.,  Publishers.) 

(Fig.  239).  Its  shape  now  resembles  that  of  a  flat  cone,  because 
while  its  tendinous  part  is  drawn 
downward  into  the  abdominal 
cavity,  its  contracted  muscular 
part  pursues  a  rather  straight 
course  between  its  place  of  origin 
and  its  insertion.  In  this  way, 
the  breadth  of  the  "comple- 
mentary" pleural  space  is  much 
increased,  thereby  allowing  the 
tapering  inferior  borders  of  the 
lungs  to  descend  into  it.  It 
should  also  be  remembered  that 
the  downward  movement  of  the 
diaphragm  is  greatly  restricted 
in  the  region  of  the  apex  of  the 
heart,  because  the  pericardial 
sac  is  here  anchored  to  its  upper 
surface.  Under  ordinary  condi- 
tions, therefore,  the  expansion 
of  the  lungs  does  not  depend  so 
much  upon  the  actual  descent  of  the  diaphragm  as  upon  the  enlarge- 
ment of  the  complementary  space.     Thus,  it  has  been  observed  by 


Fig.  239. — Diagram  Showing  the  Posi- 
tion OF  THE  DiaPHRA(}M  AND  ADJOINING  WaLL 

of  THE  Trunk  on  Inspiration  and  Expira- 
tion. 

E,  expiration;  J,  inspiration.  The  dia- 
phragm moves  downward  and  the  walls  of 
the  trunk  outward,  increasing  the  size  of 
the  complementary  space  C.  The  slight 
depression  at  H  is  caused  by  the  apical  por- 
tion of  the  heart. 


464  RESPIRATION 

means  of  the  Rontgen  rays  that  the  vertical  diameter  of  the  chest  is 
increased  by  only  10  mm.  in  the  central  area  of  the  diaphragm,  and 
while  forced  inspiration  gives  rise  to  a  somewhat  greater  descent 
(12  to  14  mm.),  the  real  pm-pose  of  diaphragmatic  respiration  seems 
to  be  to  draw  the  inferior  borders  of  the  lungs  into  the  complement aiy 
space  and  to  act  upon  the  lower  areas  of  these  organs.  Their  upper 
areas  are  also  expanded,  but  in  a  much  smaller  measure.  On  this 
account,  pleuritic  adhesions  are  more  likely  to  form  in  the  upper 
recesses  of  the  intrapleural  space,  and  catarrhal  and  tuberculous 
infiltrations  are  particularly  liable  to  affect  the  more  poorly  ventilated 
tips  of  these  organs. 

As  the  diaphragm  descends,  it  pushes  the  neighboring  abdominal 
viscera  downward,^  but  their  displacement  is  only  made  possible  by 
the  outward  bulging  of  the  anterior  and  lateral  abdominal  walls. 
In  this  way,  the  contracting  diaphragm  places  the  latter  under  a 
certain  elastic  tension.  In  other  words,  its  muscular  energy  is  tempo- 
rarily transformed  into  potential  energy*  which  is  again  made  use  of 
during  the  succeeding  expiration  in  forcing  the  abdominal  viscera 
and  overlying  diaphragm  back  into  their  original  position.  It  need 
scarcely  be  emphasized  that  the  direct  mechanical  effect  of  this  move- 
ment is  far  reaching,  because  it  favors  not  onlj^  the  venous  return  from 
the  posterior  extremities  and  organs  of  the  abdomen  but  also  that 
from  the  anterior  parts  of  the  body.^  In  addition  it  exerts  an  im- 
portant influence  upon  the  flow  of  the  lymph  and  bile.  It  should 
also  be  remembered  that  the  "aspirator^-  power  of  the  thorax"  which 
is  responsible  for  the  negativity'  of  the  venous  blood  pressure,  maj'  in 
large  part  be  ascribed  to  the  acti\'ity  of  the  diaphragm. 

In  lean  persons  the  movements  of  this  septum  are  frequently 
indicated  upon  the  external  surface  of  the  chest  by  a  furrow-hke 
depression,  the  so-called  linea  diaphragmatica,  which  progresses 
wave-like  over  the  lower  intercostal  spaces.  In  as  much  as  this 
retraction  follows  in  the  wake  of  the  contracting  muscular  brim  of 
the  diaphragm,  it  is  indicative  of  the  strength  of  the  aspiration  and  of 
the  force  with  which  the  atmospheric  pressure  tends  to  push  the  thoracic 
wall  of  this  region  inward.  This  retraction  may  be  made  to  appear 
in  almost  anj'  person  by  forcing  the  respiratory  movements.  It  is 
also  of  interest  to  note  that  the  contractions  of  the  diaphragm  are 
prolonged,  simulating  the  "tetanic"  contractions  of  striated  muscle 
tissue  when  subjected  to  a  quickly  interrupted  current  of  brief  dura- 
tion.^    Clearly,  this  mode  of  contraction,  which  insures  the  fullest 

1  The  earlier  conception,  that  the  pleural  cavity  is  filled  with  air  and  that  the 
lungs  contract  actively,  was  proved  to  be  erroneous  by  Haller,  his  evidence  being 
based  upon  observations  of  the  movements  of  the  diaphragm  and  adjoining 
pulmonary  tissue  made  through  the  thinned  tissue  of  the  lower  intercostal  space. 
See:  Do  diaphragmate,  Gottingen,  1741. 

^  Burton-Opitz,  Am.   Jour,  of  Physiol.,  xxxvi,  1914,  64. 

3  Majkwald,  Zeitschr.  fiir  Biol.,  xxiii,  1887,  149. 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS  4Go 


1^ 


possible  expansion  of  the  liinjz;s,  points  toward  a  certain  difference  in 
the  structure  or  constitution  of  tlie  diaphragmatic  myoplasm. 

The  increase  in  the  anteroposterior  and  transverse  diameters  of  the 
chest  is  effected  in  the  following  manner:  Posteriorly,  the  heads  of 
the  different  ril)s  are  in  articulation  with  the  vertebral  column  forming 
here  partially  movable  joints.  Anteriorly,  on  the  other  hand,  the  first 
ten  pairs  of  ribs  are  anchored  to  the  sternum  by  the  costal  cartilages, 
the  upper  seven  of  them  being  connected  with  this  bone  directly  and 
the  lower  three  indirectly,  while  the  eleventh  and  twelfth  pairs  of 
ribs  remain  free  and  functionally  constitute  a  part  of  the  abdominal 
wall.  When  at  rest,  the  different  ribs  in- 
cline obliquely  downward  and  forward,  so 
that  their  anterior  extremities  come  to  lie  at 
a  lower  level  than  their  posterior.  During  in- 
spiration they  are  elevated  and  rotated  out- 
ward, this  movement  being  made  possible  by 
the  flexibility  of  the  costal  cartilages  and  the 
yielding  character  of  the  costochondral  and 
chondrosternal  articulations.  It  is  evident 
that  the  lessening  of  the  obliquity  of  the  ribs 
increases  the  distance  between  the  sternum 
and  the  spinal  column;  moreover,  inasmuch 
as  the  different  pairs  of  ribs  form  rings,  the 
diameters  of  which  steadily  increase  from 
above  downward  until  the  seventh  pair  has 
been  reached,  it  necessarily  follows  that  theii- 
elevation  also  increases  the  breadth  of  the 
thorax.  Thus,  the  seventh  rib  is  raised  to  the 
level  previously  occupied  by  the  sixth,  and  the 
sixth  to  that  of  the  fifth,  and  so  on  until  the 
first  has  been  reached.  In  addition,  it  is  to 
be  noted  that  the  elevation  of  the  ribs  is  as- 
sociated with  a  slight  outward  rotation  at 
their  angles.     This  may  be  gathered  from  the 

fact  that  their  external  surfaces  are  turned  outward  and  downward 
on  expiration,  and  directly  outward  on  inspiration.  This  rotation 
alone  is  sufficient  to  increase  the  transverse  diameter  of  the  chest. 

Each  rib  articulates  with  the  spinal  column  in  two  places.  Its 
head  lies  in  contact  with  the  body  of  the  vertebra  and  its  tubercle 
with  the  transverse  process.  In  moving  upward  the  different  ribs 
rotate  around  an  axis  drawn  through  these  two  points,  but  inasmuch 
as  their  shafts  are  directed  obliquely  downward  on  expiration,  their  ele- 
vation during  inspiration  forces  their  sternal  ends  farther  outward  and 
away  from  the  spinal  column.  Although  this  movement  is  greatly  re- 
stricted, because  the  ribs  are  not  freely  movable  upon  the  sternum, 
these  articulations  are  rendered  more  yielding  by  the  interposition 

30 


Fig.  240. — Diagram  to 
Illustrate  the  Effect  of 
THE  Slant  of  the  Ribs. 

»S,  the  spinal  column;  a, 
the  position  of  the  rib  in 
normal  expiration;  a'  its 
position  (exaggerated)  in 
inspiration.  The  distance 
between  the  spinal  column 
and  the  sternum  (si.),  i.e., 
the  anteroposterior  diam- 
eter of  the  chest  is  in- 
creased). {American  Text- 
hook  of  Physiology.) 


466 


RESPIRATION 


of  the  costal  cartilages.     During  inspiration  these  cartilaginous  seg- 
ments are  subjected  to  an  eversion  and  slight  torsion. 

The  Inspiratory  Movement. — It  need  scarcely  be  emphasized  that 
the  space  which  is  added  to  the  thoracic  cavity  during  inspiration,  is 
immediately  taken  up  by  lung  tissue.  In  this  way  the  more  fully 
expanded  organs  are  capable  of  accommodating  that  extra  amount 
of  air  which  is  required  for  the  oxidative  processes  of  the  body.  As 
has  been  stated  above,  the  inspiratory  movement  is  participated 
in  by  a  number  of  muscles  which  are  designed  as  the  muscles  of  inspira- 
tion.    They  are  classified  further  as  intrinsic  and  extrinsic,  because 

some  of  them  are  actual  constituents  of 
the  walls  of  the  thorax,  while  others  arise 
elsewhere  and  are  merely  attached  to  its 
framework.  Furthermore,  inasmuch  as 
many  of  these  muscles  are  brought  into 
play  only  during  forced  or  labored  res- 
piration, it  is  customary  to  divide  them 
into  normal  and  accessory  muscles  of 
inspiration. 

As  normal  muscles  of  inspiration  are 
to  be  regarded  the  diaphragm,  the  inter- 
costales  externi  and  the  serratus  posticus 
superior,  and  as  accessory  muscles  the 
scalenus  anticus,  medius  et  posticus,  the 
sternocleidomastoideus,  trapezius,  pec- 
torales  major  et  minor,  rhomboides 
major  et  minor  and  serratus  anticus. 
The  levatores  costarum  longi  et  breves, 
which  are  sometimes  classified  under  the 
first  heading,  do  not  participate  in  the 
raising  of  the  ribs  and  belong  to  the 
muscle  system  of  the  vertebral  column.^ 

Under  ordinary  conditions,  the  action  of  the  normal  muscles  of 
inspiration  is  adjusted  in  such  a  way  that  the  diaphragm  assumes  a 
preponderating  role;  in  fact,  this  muscle  alone  almost  suffices  to  carry 
on  a  proper  interchange  of  the  gases  as  long  as  the  body  is  only  mod- 
erately active.  But  when  an  additional  supply  of  air  is  needed,  other 
muscles  are  brought  into  play;  the  lower  intercostals  being  activated 
first,  and  subsequently  the  upper  intercostals  and  accessory  muscles. 
In  this  way,  the  previously  diaphragmatic  or  abdominal  type  of  respira- 
tion is  converted  into  the  costal  type.  Hutchinson^  states  that  in 
abdominal  breathing  the  abdomen  is  seen  to  bulge  out  before  the 
thorax  is  moved  upward,  while  in  costal  breathing  the  elevation  of 
the  ribs  occurs  first. 


Fig.  241. — Sixth  Dorsal  Vertebra 
AND  Rib.     (Reichert.) 


1  Du  Bois-Reymond,  Ergebn.  der  Physiologic,  ii,  1902,  387. 

2  Todd's  Cyclopaedia  of  Anatomy  and  Physiology,  1849. 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS 


467 


Under  ordinary  conditions,  however,  these  terms  are  iiserl  only  in  a 
relative  way  to  indicate  whether  the  diaphragm  and  lower  intercostals 
or  the  upper  costal  and  intercostal  muscles  are  the  chief  factors  in 
respiration.  It  is  customary  to  state  that  the  respiration  in  men  is 
diaphragmatic,  while  that  of  women  is  costal.*  By  some  investigators 
this  greater  mobility  of  the  thorax  in  the  female  is  regarded  as  a  sexual 
characteristic,  while  others  hold  that  it  is  the  artificial  result  of  a 
long-continued  constriction  of  the  waist  and  encasement  of  the  abdo- 
men. If  regarded  as  a  sexual  characteristic,  it  may  be  said  to  pro- 
tect the  developing  fetus  against  an  undue  intra-abdomi- 
nal pressure,  and  to  help  the  mother  in  retaining  her 
normal  respiratory  capacity.  The  more  recent  investi- 
gations, however,  do  not  uphold  this  view,  because  it 
has  been  shown  that  Indian  and  Chinese  women,  who 
have  never  worn  corsets,  show  the  abdominal  type  of 
breathing.  2  This  is  also  true  of  white  women  who  have 
not  been  in  the  habit  of  wearing  tight-fitting  clothes  or 
have  discarded  the  corset  in  later  years.  Thus,  while  it 
seems  certain  that  the  preponderance  of  costal  breath- 
ing in  woman  does  not  possess  a  physiological  basis, 
gestation  no  doubt  throws  the  burden  of  respiration 
temporarily  upon  the  thorax,  until  at  the  end  of  this 
period  the  play  of  the  diaphragm  can  again  go  on  un- 
hinderedly.  In  visceroptosis  the  action  of  the  diaphragm 
is  greatly  restricted  and  costal  breathing  is  brought 
into  play  more  and  more. 

In  some  animals  the  diaphragm  presents  a  rounded 
outHne  and  its  tendinous  portion  is  placed  in  the  center 
between  the  sternum  and  the  vertebral  column.  In 
others  it  is  arranged  bilaterally,  its  antero-posterior  di- 
ameter in  the  region  of  the  sternum  being  shorter  than 
its  transverse  or  oblique  diameter.  Each  half  is  inner- 
vated by  the  corresponding  phrenic  nerve  which  arises 
from  the  third  and  fourth  cervical  spinal  nerves  and 
passes  downward  through  the  thorax  in  close  proximity 
to  the  heart.  The  division  of  one  of  these  nerves  is 
immediately  followed  by  a  paralysis  of  the  corresponding  half  of  the 
diaphragm,  while  the  division  of  both  nerves  gives  rise  to  a  uselessness 
of  the  entire  muscle.  The  latter  procedure  generally  proves  fatal,  and 
especially  in  3'oung  animals,  because  the  respiratory  interchange  then 
becomes  wholly  inadequate.  In  this  connection  mention  might  also 
be  made  of  the  fact  that  the  quiescent  diaphragm  contracts  at  times 
synchronously  with  the  heart.  This  phenomenon,  which  may  be  ob- 
tained with  the  chest  open  or  closed,  seems  to  require  a  certain  high 
degree  of  nervous  excitability,  either  local  or  general.     The  action 

^  Hasse,  Archiv  fiir  Anatomie,  1903,  23. 
2  Fitz,  Jour,  of  Exp.  Med.,  i,  1896. 


Fig.    242. 

D I AGBAM 

Showing     the 

E  N  li  ARGEMENT 

OF  THE  Trunk 
ON  Normal, 
( D  iaphragma- 
Tic)  AND  For- 
ced (Costal) 
Respiration. 


468 


RESPIRATION 


current  arriving  in  the  ventricles  is  then  propagated  to  the  left  phrenic 
nerve,  because  this  nerve  lies  in  close  contact  with  the  cardiac  apex. 
Moreover,  as  the  diaphragmatic  muscle  reacts  more  quickly  than  the 
ventricular,  the  former  is  generally  seen  to  twitch  before  the  systole  of 
the  ventricles  has  fully  developed.^ 

The  Action  of  the  Intercostal  Muscles. — The  ribs  are  connected 
with  one  another  by  two  sets  of  muscles,  known  as  the  intercostals. 
The  external  intercostals  extend  obliquely  downward  and  forward,  their 
attachment  upon  the  rib  above  being  nearer  the  spinal  column  than 
their  insertion  upon  the  rib  below.  The  internal  intercostals  pass  in 
the  opposite  direction,  their  place  of  attachment  upon  the  rib  below 
being  nearer  the  spinal  column  than  their  insertion  upon  the  rib  above. 
The  action  of  these  muscles  may  readily  be  deduced  from  the  adjoining 
schema  (Fig.  243)  if  it  is  remembered  that  a  contracting  muscle  causes 
its  point  of  insertion  to  move  closer  to  its  point  of  attachment.     If 


S    J 


Fig.  243. — Diagr,ajvi  Illustratixg  the  Action  of  the  Intehcostal  Muscles. 
S,  sternum ;  F,  vertebral ;  A  and  B  two  consecutive  ribs ;  £'£'1,  external  intercostal  mus- 
cle; JJi,  internal  intercostal  muscle.    The  contraction  of  the  first  raises  the  ribs  (//) ,  while 
the  contraction  of  the  second  lowers  them  (III).     The  distance  SV  is  now  shortened. 

A  and  B  represent  two  consecutive  ribs,  the  posterior  extremities 
of  which  are  movable  upon  the  vertebral  column,  but  relatively 
immovable  upon  the  sternum,  the  line  E  to  Ei  indicates  the  direction 
of  the  external  intercostal  fibers  and  the  line  J  to  Ji  that  of  the  inter- 
nal intercostal  fibers  (Fig.  243,  /).  If  the  first  muscle  is  now  made  to 
contract,  the  ribs  assume  the  position  shown  in  Fig.  243,  //,  because  the 
distance  between  the  two  ends  of  the  different  external  intercostal  fibers 
has  been  shortened.  This  muscle,  therefore,  elevates  the  ribs  and 
is  inspiratory  in  its  action.  If  the  second  muscle  is  now  made  to 
contract,  J  is  brought  nearer  to  Ji  and  the  ribs  are  depressed  (Fig. 
243,  777).  The  internal  intercostals,  therefore,  are  expiratorj'  in  their 
function. 

A  similar  but  more  elaborate  representation  of  the  action  of  the  intercostal 
and  intercartilaginous-  muscles  has  been  given  by  Hamberger,  in  1727,  but  the 

1  Pike,  Am.  Jour,  of  Physiol.,  xl,  1916,  433. 

^  The  muse,  intercartilaginei  constitute  that  part  of  the  muse,  intercostales 
interni  which  is  situated  between  the  costal  cartilages. 


THE  MKCHANICS  OF  THE  RESPIRATORY  MOVEMENTS 


469 


corrpctness  of  this  oxplaniition  has  lioon  quostioned  by  A.  v.  Ilallor,  who  regarded 
both  intercostals  as  insjjiratory  in  their  function.  As  is  indieated  in  Fig.  214, 
two  bars  are  arranged  in  such  a  way  a.s  to  represent  two  adjoining  rib.s  {A  and  li) 
suspended  from  the  vertebral  column  and  united  in  front  with  the  costal  cartilages 
a  and  b,  and  the  sternum  {S).  The  external  intercostal  and  iritcrcartilaginou.s 
muscles  are  represented  by  rubber  bands,  placed  in  the  position  fJ  and  E\,  and 
J  and  J I  respectively.  If,  to  begin  with,  the  parallel  bars  are  depressed  sufficiently 
to  place  the  rubber  bands  under  elastic  tension  (Fig.  244,  /),  their  rclea.se  is  imme- 
diately followed  by  an  upward  movement  (Fig.  244,  //)  for  the  reason  that  the 
elastic  forces,  although  acting  in  opposite  directions,  are  equal,  and  as  thej^  are 
exerted  in  a  parallelogram,  the  component  acting  upward  on  the  long  arm  of  the 
lever  exceeds  the  component  acting  downward  on  the  .short  arm  of  the  lever. 
Moreover,  as  the  distance  between  the  consecutive  ribs  i.s  fixed,  their  upward 
movement  must  increa.se  the  angle  between  them  and  the  costal  cartilages,  and 
must  also  lead  to  a  forward  movement  of  the  sternum. 


Fig.  244.^- Diagram  Illvstratixg  the  Action  of  the  External  Intercostal  ant) 
Intercartilaginei  Muscles. 
V,  vertebral  column;  S,  sternum;  AB,  two  consecutive  ribs;  ab,  their  costal  cartilages; 
EEi,  external  intercostal;  JJi,  intercartilaginei  muscles;  I,  position  at  end  of  expiration, 
when  these  muscles  are  under  tension ;  //,  po-sition  at  end  of  inspiration  when  these  muscles 
have  contracted,  raising  the  ribs  and  pushing  the  sternum  forward. 

While  the  action  of  the  external  and  internal  intercostal  muscles 
has  been  a  subject  of  much  controversy,  it  is  commonly  held  to-day 
that  the  former  elevate  and  the  latter  depress  the  ribs.  For  this 
reason,  the  external  one  should  be  classified  as  an  inspiratory,  and  the 
internal  one  as  an  expiratory  muscle.  It  is  to  be  noted,  however,  that 
they  are  not  activated  at  the  same  time,  because  those  placed  between 
the  lower  ribs  serve  as  an  aid  to  the  diaphragm  and  are  seldom  at  rest, 
whereas  those  situated  between  the  upper  ribs  remain  inactive  for 
long  periods  of  time  until  a  fuller  expansion  of  the  lungs  is  required. 
Besides,  it  should  not  be  forgotten  that  the  intercostal  muscles  serve 
as  tensors  of  the  intercostal  spaces.  As  Landois^  has  shown,  if  the  soft 
parts  between  the  ribs  were  perfectly  flabby,  they  would  be  pulled 
inward  by  the  elastically  recoihng  lung,  and  more  markedly  so  during 
the  inspiratory  movements.  Obviously,  the  alternate  contraction 
of  these  muscles  prevents  this  bellying  inward  during  practically  the 

iLehrbuch  der  Physiol.,  i,  1909,  190. 


470  EESPIRATION 

entire  respiratory  cycle  and  keeps  the  lungs  in  the  fullest  possible 
state  of  expansion.  Moreover,  their  action  as  tensors  immediately 
assumes  a  much  greater  functional  importance  if  the  respiratory 
motions  become  forced  or  if  the  intrathoracic  pressures  are  momen- 
tarily greatly  increased  or  decreased.  Conditions  of  this  kind  arise, 
for  example,  during  the  acts  of  coughing  and  sneezing  and  during 
sudden  inspiratory  efforts,  such  as  are  required  during  speaking  and 
singing.  At  this  time  the  contracting  intercostal  muscles  actually 
protect  the  thorax  and  its  contents  against  injury,  just  because  they 
prevent  the  outward  and  inward  bellying  of  its  intercostal  septa. 

The  Expiratory  Movement. — Expiration,  as  has  been  stated  above, 
is  largely  a  passive  process  in  which  three  factors  play  a  part,  namely 
gravity,  the  recoil  of  the  stretched  tissues,  and  muscular  activity.  In- 
asmuch as  the  thorax  is  raised  during  inspiration,  there  must  be  pres- 
ent a  tendency  on  the  part  of  the  ribs,  sternum  and  soft  structures  to 
resume  their  former  position  on  account  of  their  weight.  This  factor, 
however,  cannot  make  itself  felt  until  the  muscular  force  acting  upon 
them  during  inspiration  has  been  made  to  cease.  This  is  also  true  of 
the  elastic  recoil  of  the  soft  and  hard  parts  constituting  the  thoracic 
wall,  and  naturally,  this  factor  makes  itself  felt  in  two  ways.  On  the 
one  hand,  we  have  the  recoil  of  the  lungs  upon  which  the  preceding 
inspiratory  movement  has  forced  a  condition  of  hyperexpansion, 
and,  on  the  other,  the  recoil  of  the  cartilaginous  and  bony  constitu- 
ents of  the  thorax  which  by  the  same  means  have  been  placed  under 
a  considerable  elastic  tension.  These  conditions  must  necessarily 
augment  one  another,  because  the  direction  of  their  action  is  toward 
the  center  of  the  thorax.  The  only  muscle  which  participates  in  the 
expiratory  movement  is  the  internal  intercostal,  but  since  quiet 
breathing  is  effected  very  largely  by  the  diaphragm  alone,  it  is  doubt- 
ful whether  much  importance  can  be  attached  to  its  action.  At  best, 
solely  the  lowermost  rows  of  this  muscle  would  be  called  into  play. 
Various  conditions,  however,  may  arise  in  which  the  elastic  forces 
must  be  promptly  and  efficiently  assisted  by  this  muscle  and  possibly 
also  by  the  triangularis  sterni.  The  latter,  in  all  probability,  depresses 
the  cartilages  and  anterior  extremities  of  the  ribs.  As  far  as  the  capac- 
ity of  the  thorax  is  concerned,  the  three  factors  just  enumerated  unite 
to  decrease  it  along  the  anteroposterior  and  transverse  planes. 

Essentially  the  same  factors  take  part  in  decreasing  the  vertical 
diameter  of  the  chest.  To  begin  with,  the  descent  of  the  diaphragm 
places  the  abdominal  viscera  under  pressure  with  the  result  that  the 
anterior  and  lateral  walls  of  the  abdomen  are  forced  outward  and  are 
put  on  the  stretch.  Below,  the  diaphragm  meets  with  the  resistance  of 
the  pelvic  floor,  and  posteriorly  with  that  of  the  vertebral  column. 
Thus,  it  is  commonly  noted  that  this  outward  movement  is  also 
participated  in  by  the  floating  ribs  and  the  lowermost  true  ribs,  but 
a  pronounced  outward  bulging  of  the  thoracic-abdominal  junction 
cannot  result  unless  the  downward  progression  of  the  diaphragm  is 


THE  MECHANICS  OF  THE  RESPIRATORY  MOVEMENTS  471 

greatly  hindered.  A  condition  of  this  kind  is  commonly  obtained  rlur- 
infi;  pregnanc'3^  or  when  t  lie  thighs  are  flexed  upon  the  abdomen.  In  the 
nature  of  things,  gravity  cannot  play  a  role  in  the  upward  movement 
of  the  diaphragm  unless  the  body  be  placed  in  a  position  directly 
favoring  this  factor.  The  elastic  recoil  of  the  tissues,  on  the  other 
hand,  is  of  paramount  importance.  In  endeavoring  to  regain  its 
normal  position,  the  stretched  abdominal  wall  pushes  the  viscera  and 
overlying  diaphragm  upward.  At  this  very  moment  the  upper  surface 
of  this  now  perfectly  passive  membrane  is  directly  exposed  to  the  elas- 
tic recoil  of  the  lungs.  It  will  be  seen,  therefore,  that  the  diaphragm 
is  made  to  assume  its  former  position  by  two  forces  applied  simul- 
taneously to  its  under  and  upper  surfaces.  The  elastic  recoil  of  the 
abdominal  wall  pushes  it  upward,  while  the  elastic  recoil  of  the  lungs 
pulls  it  upward. 

In  forced  expiration  the  capacity  of  the  thorax  is  decreased  still 
further  by  the  contraction  of  several  abdominal  and  thoracic  muscles. 
Besides  the  internal  intercostals  and  the  triangularis  sterni,  mention 
should  be  made  at  this  time  of  the  abdominales,  serratus  posticus 
inferior,  and  quadratus  lumborum.  Obviously,  the  latter  augment  the 
power  of  the  recoil  so  that  the  abdominal  organs  are  pushed  against 
the  inferior  surface  of  the  diaphragm  with  an  even  greater  force  than 
during  normal  expiration. 

Accessory  Movements  of  Respiration. — The  muscles  to  which 
reference  has  just  been  made,  are  concerned  with  the  respiratory  varia- 
tions in  the  capacity  of  the  thoracic  cavity  and  hence,  with  the 
expansion  of  the  lungs.  Besides  these  a  number  of  other  muscles 
might  be  mentioned  which  give  rise  to  certain  associated  respiratory 
movements  of  the  nostrils,  pharynx  and  larynx.  Thus,  it  may  be 
noticed  that  the  orifices  of  the  external  nares  are  dilated  during 
inspiration  and  constricted  during  expiration.  The  former  movement 
is  produced  by  the  contraction  of  the  elevators  of  the  alse  of  the  nose, 
while  the  latter  is  the  result  of  the  elastic  recoil  of  these  parts.  Ob- 
viously, the  purpose  of  this  movement  is  to  lessen  the  resistance  to 
the  inflow  of  air.  A  similar  rhythmic  widening  of  the  respiratory 
passage  occurs  in  the  larynx,  where  the  vocal  cords  are  placed  in 
the  path  of  the  current  of  air  for  purposes  of  phonation.  The  space 
between  their  free  edges,  the  glottis,  is  enlarged  during  inspiration  and 
narrowed  during  expiration.  The  former  effect  is  dependent  upon 
the  contraction  of  the  posterior  crico-arytenoid  muscles  which  abduct 
the  tips  of  the  arytenoid  cartilages  to  which  the  posterior  extremities 
of  the  vocal  cords  are  attached.  The  muscles  of  the  neck  and  face  may 
be  made  to  contract  rhythmically  by  rendering  the  respiratory  move- 
ments more  labored  (dj^spnea).  It  is  also  claimed  that  the  caliber 
of  the  bronchi  is  increased  during  inspiration  and  decreased  during 
expiration. 

Classification  of  the  Respiratory  Muscles. — The  preceding  dis- 
cussion, no  doubt,  has  shown  that  it  is  difficult  to  give  a  perfectly 


472  RESPIHATION 

accurate  classification  of  the  muscles  which  take  part  in  the  expansion 
of  the  lungs.  The  following  table,  however,  may  serve  as  a  general 
guide. 

A.  Inspiration. 

1.  Normal. 

Diaphragm  (nerv.  phrenicus). 

Muse,  intercost.  externi  et  intercartilaginei  (nerv.  intercostales). 

2.  Forced. 

a.  Muscles  of  the  Trunk. 

Muse,  sealeni  (nerv.  plex.  cerv.  et  brachiahs). 

Muse,  serratus  posterior  superior  (nerv.  intercostales). 

Muse,  serratus  anterior  magnus  (nerv.  thor.  longus). 

Muse,  pectoralis  major  et  minor  (nerv.  thor    ant.). 

Muse,    sternocleidomastoicleus    (nerv.    aecessori). 

Muse,    trapezius    (nerv.    accessorii). 

Muse,  extensores  eolumnce  vertebralis  (ram.  post.  nerv.  dors.). 

Muse,   rhomboidei    (nerv.   dors,   scapulse). 

Muse,  levator  scapulae  (nerv.  dors,  scapulae). 

b.  Larynx. 

Muse,  sternohyoideus  (nerv.  ram.  disc,  hypoglossi). 
Muse,  sternothyreoideus   (nerv.   ram.   disc,   hypoglossi). 
Muse,    crieoarytenoideus    (nerv.   lar.   inferior). 

c.  Pharynx. 

Muse,  levator  veli  palatini  (nerv.  facialis). 

Muse,    azygos    uvula?. 

Muse,  constrictores  pharyngis  (nerv.  glossoph.  et  vagus). 

d.  Face. 

Muse.  dil.  narium  ant.  et  post.   (nerv.  facialis). 
Muse,  levator  alse  nasi  (nerv.  facialis). 

B.  Expiration. 

1.  Normal. 

Gravity  and  elastic  recoil  of  the  lungs,  intercostal  cartilages  and  abd. 
muscles. 

2.  Forced. 

Muse,  intercostales  interni  (nerv.  intercostales). 

Muse,  abdominales. 

Muse,  triangularis  sterni  (nerv.  intercostales). 

Muse,  serratus  post,  inferior  (ram.  ext.  nerv.  dors.). 

Muse,  quadratus  lumborum   (ram.  muse,  e  plexa  lumbali). 


CHAPTER  XXXVIII 

THE  FREQUENCY  AND  CHARACTER  OF  THE  RESPIRA- 
TORY MOVEMENTS 

Methods  of  Recording  the  Respiratory  Movements. — The  early 
measurements  of  the  diameter,  of  the  thorax  made  with  the  help  of  a 
tape-measure  and  large  calipers,  were  soon  superceded  by  the  registra- 
tion of  the  movements  of  the  chest  by  means  of  levers  placed  horizon- 
A^         tally   upon   its    external   surface, ^  or   by    means   of   an   instrument 

'Vierordt  and  Ludwig,  Arch,  fiir  physiol.  Heilkunde,  xiv,  1855,  253,  and  Riegel, 
Die  Athembewegungen,  Wiirzburg,  1873. 


FREQUENCY  AND   CHARACTER  OF  RESPIRATORY  MOVEMENTS      473 

niodoled  ufter  the  sphyp;mop;raph.  A  \cry  simple  steOwgraph  may  he 
made  by  applying  an  ordinary  rubber  bulb  to  the  surface  of  the  chest 
by  means  of  a  tape  and  by  connecting  its  orifice  with  a  recording 
tambour.  Marey^  has  advocated  the  use  of  a  rubber  tube  closed  at 
its  ends  and  fastened  around  the  chest.  This  tube  is  connected  V^y 
means  of  a  cannula  with  a  recording  drum  which  then  responds  to 
the  changes  in  pressure  caused  by  the  respiratory  movements.  Later 
on  this  pneumograph  took  the  form  of  a  metallic  tambour  placed 
directly  over  a  narrow  plate  of  steel.  When  properly  applied  to  the 
surface  of  the  chest,  the  respiratory  movements  subject  this  plate  to 
different  degrees  of  tension  which  are  transferred  by  a  lever  to  the  rub- 
ber membrane  of  the  tambour  (Fig.  245).  Another  method  fre- 
quently practised  is  to  register  the  variations  in  the  intrapleural 
pressure  by  means  of  a  tambour  connected  with  the  intrapleural  space. 
In  a  similar  way,  the  intrathoracic  pressure  may  be  recorded  with  the 
help  of  a  tambour  connected  with  a  catheter  which  is  passed  down  the 


Fig.  245. — Dl^gram  of  Makey's  Pneumograph. 
The  instrument  consists  of  a  tambour  (i),  mounted  on  a  flexible  metal  plate  (p). 
By  means  of  the  bands  c  and  c  the  metal  plate  is  tied  to  the  chest.  Any  increase  or 
decrease  in  the  size  of  the  chest  will  then  affect  the  tambour  by  the  lever  arrangement 
shown  in  the  figure.  These  changes  in  the  tambour  are  transmitted  through  the  tube  r 
as  pressure  changes  in  the  contained  air  to  a  second  tambour  (not  shown  in  the  figure) 
which  records  them  upon  a  smoked  drum.     (American  Text-book  of  Physiology.) 

esophagus  until  its  free  end  comes  to  lie  a  short  distance  above  the  dia- 
phragm. It  is  also  possible  to  insert  a  T  tube  in  the  trachea  and  to 
connect  its  lateral  branch  with  a  recording  tambour,  or  to  permit  the 
animal  to  respire  through  a  large  bottle,  one  of  the  outlets  of  which 
communicates  with  a  recording  instrument.  If  the  abdomen  has  been 
opened,  the  diaphragm  may  be  connected  with  a  writing  lever  by  means 
of  a  small  hook  and  thread  acting  over  a  pulley.  It  has  also  been  advo- 
cated to  separate  the  ensiform  cartilage  from  the  manubrium  of  the 
sternum  and  to  attach  it  by  means  of  a  thread  to  an  ordinary  writing 
lever. 

Pneumatogram. — A  record  of  the  respiratory  movements  consists 
as  a  rule  of  a  series  of  waves  composed  of  alternate  upstrokes  and 
downstrokes,  but  whether  the  inspiratory  period  is  represented  by  the 
ascending  limb  or  by  the  descending  limb  depends  upon  the  manner 
of  action  of  the  recording  instrument.  Thus,  INIarej^'s  pneumograph 
acts  aspiratingly,  pulling  the  lever  of  the  recording  tambour  downward 

^La  methode  graphique,  Paris,  1873;  also  see:  Brondgeestsche,  Onderzoek, 
g.  i.  h.  physiol.  Lab.,  Utrecht,  ii,  1S7.3,  326. 


474  RESPIRATION 

during  inspiration,  while  an  ordinary  rubber  bulb  yields  a  positive 
pressure  during  this  period,  and  forces  the  writing  lever  upward. 

The  inspiratory  movenaent  sets  in  gradually.  It  acquires  a  con- 
siderable speed  in  its  intermediate  phase  but  again  becomes  slow 
toward  its  end.  Expiration  is  slow  at  first,  rather  rapid  in  its  inter- 
mediate phase  and  decidedly  slow  toward  its  end.  In  general, 
therefore,  inspiration  sets  in  more  abruptly  than  expiration  and  occu- 
pies a  somewhat  shorter  time  than  expiration,  the  relationship  between 
these  periods  being  as  10  :  14.  Furthermore,  while  the  exTDiratory 
movement  follows  immediately'  upon  the  completion  of  inspiration, 
the  next  inspiratory^  motion  is  not  Vjegun  until  a  few  moments  later. 
It  is  to  be  noted,  however,  that  a  true  pause  is  not  developed  at  this 
time  in  spite  of  the  fact  that  the  muscles  are  perfectly  quiescent. 
This  must  necessarilj'  be  so,  because  the  elastic  forces  are  at  play  even 
during  this  interim  of  relative  "rest,"  tending  to  retain  the  chest  in  a 
semi-active  or  '"'set "  condition.  It  is  also  a  matter  of  common  experi- 
ence that  the  action  of  the  respiratory  muscles  may  be  arrested  at 


E  ^  ^ 

Fig.  246. — Pn-ex3iatogr.vm  Poxxjeded  et  Coxn-ecttsg  the  Lnt&apleueax  Space  With 

A  Mevbrave  Maxometeb. 
J,  Insp.  movement;  E,  expir.  movement.     The  figures  indicate  the  negative  pressure 
recorded  during  these  resp.  cycles. 


any  time  during  the  respirator^'  cycle.  Ordinarily,  however,  the 
desire  to  resume  this  activity  becomes  imperative  in  less  than  a  minute, 
owing  to  the  accumulation  of  excessive  amounts  of  carbon  dioxid' 
But  if  the  system  is  first  thoroughly  ventilated  and  .surcharged  with 
oxj'gen  by  a  series  of  forced  respiratory  movements,  the  breath  may 
be  held  for  a  much  longer  period  of  time.  Professional  divers,  for 
example,  are  capable  of  remaining  under  water  for  several  minutes. 
The  number  of  respirations  in  a  given  period  of  time  vary  with 
the  conditions  under  which  the  animal  lives.  In  the  adult  human 
being  from  16  to  20  cycles  are  completed  in  the  course  of  one  minute, 
their  average  number  being  18.  It  is  also  to  be  noted  that  the  respira- 
tory frequency  is  greater  when  the  person  assumes  the  erect  position 
than  when  recumVjent  or  sitting  down.  Naturally,  this  change  is 
in  accordance  with  the  oxygen  requirement,  the  mere  act  of  rising 
necessitating  a  greater  muscular  activity  and  metabolism.  An  impor- 
tant influence  is  also  exerted  by  age,  as  may  be  gathered  from  the 
following  compilation: 


FREQUENCY  AND   CHARACTER  OF  RESPIRATORY   MOVEMENTS      475 

Respirations 

in  a 

minute 

New-born 62 

0-  1  year 44 

5-15  years 26 

15-20  years 20 

20-25  years 18. 7 

25-30  years 15 

30-50  years 17 

The  fact  that  the  respiratory  frequency  varies  in  accordance  with 
the  intensity  of  the  metabohsm  may  be  proved  in  several  ways.  Thus 
it  is  readily  noticed  that  muscular  exercise  and  glandular  activity 
increase  it,  while  sleep  diminishes  it.^  A  heightened  respiratory 
activity  is  usually  associated  with  rises  in  the  temperature  of  the  body 
or  of  the  surrounding  air  (heat  dyspnea).  A  similar  effect  is  pro- 
duced by  increases  in  the  barometric  pressure  and  in  the  carbon  di- 
oxid  content  of  the  inspired  air.  The  frequency  of  respiration  and 
the  size  of  the  animal  preserve  an  indirect  relationship  to  one  another, 
because  the  smaller  animals  possess  a  more  extensive  body-surface 
in  relation  to  their  mass  than  the  larger  ones,  and  hence,  suffer  a 
much  greater  loss  of  body-heat.  This  greater  dissipation  necessitates 
a  more  rapid  production  of  heat,  i.e.,  a  more  active  metabolism.  The 
latter  is  invariably  characterized  by  a  greater  respiratory  frequency.^ 

The  wide  differences  noted  in  different  species  are  made  apparent  by 
the  following  table : 

Horse 6-10 

Ox 10-15 

Sheep ,. 12-20 

Dog 15-25 

Pig 15-20 

Man 16-24 

Cat 20-30 

Pigeon 30 

Rabbit 50-60 

Sparrow 90 

Guinea-pig 100-150 

Rat 100-200 

The  rhythm  of  respiration  is  also  disturbed  by  emotions  and  during 
the  production  of  sounds,  such  as  are  used  in  speaking.  In  health 
a  fairly  constant  ratio  of  1  : 4  is  maintained  between  the  rate  of  respira- 
tion and  that  of  the  heart.  It  is  also  true  that  this  ratio  is  frequently 
retained  even  under  pathological  conditions,  because  the  respiratory 
and  cardiac  activities  are  subject  to  practically  the  same  influences 
and  react  toward  them  in  an  almost  identical  manner. 

The  Changes  in  the  Position  of  the  Lungs. — The  expansion  of  the 
lungs  gives  rise  to  a  change  in  their  volume  and  hence,  also  in  their 

1  Chait,  Dissertation,   Zurich,   1907,    Dohrn,    Zeitschr.   fur   Geburtsh.,   xxxii, 
1895,  25,  and  Recklinghausen,  Pfliiger's  Archiv,  Ixii,  1896,  451. 
^  Johanson,  Skand.  Archiv  fiir  Physiol.,  1895,  20. 


476  RESPIRATION 

position  within  the  thoracic  cavity.  Posteriorly,  these  organs  meet 
with  the  resistance  of  the  vertebral  column,  and  above,  with  that  of  the 
structures  situated  at  the  ba-se  of  the  neck.  Centrally,  their  enlarge- 
ment is  opposed  bj'  the  heart  and  large  blood-vessels  For  this  reason, 
they  seek  in  general  a  downward  and  outward  course,  their  roots  mov- 
ing downward  and  forward  and  their  anterior  margins  downward 
and  inward.  These  changes  enable  their  borders  to  move  closer 
together.  Their  exact  boundaries  may  be  made  out  at  any  time  by 
the  method  of  percussion  which  consists  in  holding  a  thin  plate  of 
rubber  firmly  against  the  external  surface  of  the  chest  and  in  sharply 
tapping  upon  it  with  a  small  bolstered  hammer  (Piorry's  pleximeter). 
A  more  convenient  procedure  is  to  apply  the  third  finger  of  the  left 
hand  to  the  chest  and  to  strike  it  with  the  bent  second  or  third  finger 
of  the  right  hand.  The  sound  elicited  in  this  waj'  Varies  with  the 
nature  of  the  subjacent  tissues.  If  the  lung  tissue  underneath  is  fully 
expanded,  a  clear  resonant  sound  is  evoked.  Consolidated  lung 
tissue,  on  the  other  hand,  imparts  a  dull  character  to  this  sound,  while 
partly  infiltrated  tissue  gives  rise  to  intermediate  notes.  The  same 
holds  true  if  the  layer  of  the  subjacent  pulmonary  tissue  is  thin. 

Anteriorly,  the  apices  of  the  Itings  are  situated  3-7  cm.  above  the 
clavicle,  and  posteriorly,  at  about  the  level  of  the  seventh  spinous 
process.  When  held  in  the  expiratory  position,  their  lower  borders 
extends  in  front  from  the  upper  edge  of  the  sixth  rib  obliquely  down- 
ward to  the  level  of  the  tenth  rib  at  the  back  of  the  chest.  A  deep 
inspiration  forces  this  boundary  do'^mward  until  it  rests  in  front, 
opposite  the  seventh  rib  and  behind,  opposite  the  eleventh  rib.  Quite 
similarly,  a  forceful  expiration  allows  their  lower  boundary  to  ascend 
to  about  the  next  ribs  above  those  mentioned  previously.  Complete 
dulness  prevails  in  the  region  of  the  heart,  but  the  size  of  this  area 
differs  with  the  degree  of  expansion  of  the  lung.  AMien  in  the  expira- 
tory position,  the  anterior  border  of  the  left  organ  remains  at  some  dis- 
tance from  the  midsternal  line,  thereby  increasing  the  cardiac  dulness 
until  it  embraces  a  triangular  space  which  is  limited  by  the  left  border 
of  the  sternum,  the  fourth  costosternal  articulation  and  the  sixth  costal 
cartilage.  In  a  robust  man  whose  arms  are  held  in  the  horizontal 
position,  the  circumference  of  the  chest  at  the  level  of  the  nipples 
measures  82  cm.  on  expiration  and  89  cm.  on  deep  inspiration.  At 
the  level  of  the  ensiform  cartilage  these  measurements  are  76  cm.  and 
83  cm.  respectively.  In  infants  and  old  people,  however,  the  cir- 
cumference of  the  lower  part  of  the  thorax  is  usually  greater ;  moreover, 
the  right  side  of  the  adult  is  prone  to  be  larger  than  the  left  on  account 
of  its  greater  muscular  development. 

Respiratory  Sounds. — If  the  ear  is  applied  to  the  chest  over  per- 
fecth'  sound  lung  tissue,  a  soft  rustling  soimd  is  heard  during  inspira- 
tion which  is  designated  as  the  vesicular  murmur.  It  is  thought  to 
arise  either  in  the  alveoli  or  at  the  point  where  the  bronchiolar  ter- 
minals open  into  the  much  larger  infundibula.     Obviously,  its  cause 


FREQUENCY  AND   CHARACTER  OF  RESPIRATORY  MOVEMENTS      477 

must  be  sought  in  the  sutklon  distention  of  the  air  vesicles  and  the  flow 
of  the  air  through  the  fine  bronchioles  into  the  enlarged  infundibula. 
The  coincidence  that  this  murmur  is  especially  distinct  in  children, 
is  referable  to  the  smaller  caliber  of  their  infundibular  spaces. 
Furthermore,  the  quality  of  this  sound  is  generally  modified  by  the 
noises  which  are  set  up  by  the  air  as  it  rushes  through  the  trachea  and 
bronchi.  They  are  transmitted  from  here  to  other  regions  of  the  pul- 
monary parenchyma.  For  this  reason,  the  general  vesicular  murmur 
is  usually  regarded  as  being  due  to  two  causes,  namely,  to  the  true 
vesicular  sound  produced  in  the  infundibula,  and  the  glottic  sound, 
generated  by  the  current  of  air  as  it  traverses  this  aperture.  Conse- 
quently, the  more  remote  regions  of  the  lung  give  rise  to  a  vesicular 
sound  of  purer  quality  than  those  situated  nearer  the  larynx.  In 
large  animals,  in  fact,  this  resonant  element  fails  to  be  transmitted 
to  the  more  distant  pulmonary  tissue  and  can  only  be  heard  in  the 
regions  adjacent  to  the  bronchioles.  It  is  possible  to  destroy  the 
glottic  element  of  the  murmur  entirely  by  permitting  the  animal  to 
breathe  through  an  opening  in  the  trachea. 

On  listening  over  the  larynx,  trachea  or  bronchi,  either  with  the 
unaided  ear  or  with  a  stethoscope,  a  loud  blowing  noise  is  heard  dur- 
ing inspiration  as  well  as  during  expiration.  It  is  called  the  bronchial 
murmur.  During  health  this  sound  is  not  audible  over  the  outlying 
districts  of  the  lung,  but  is  propagated  into  these  regions  if  the  alveoli 
are  deficient  in  air.  A  condition  of  this  kind  arises  quite  commonly 
from  compression  of  the  pulmonary  parenchyma  or  in  consequence 
of  exudations  of  inflammatory  material  (pneumonia)  and  hence, 
bronchial  breathing,  over  any  part  of  the  lung  other  than  that  adjoin- 
ing the  larger  air-tubes  is  always  indicative  of  consolidation  of  this 
tissue.  It  might  also  be  mentioned  that  the  absence  of  these  sounds 
does  not  necessarily  imply  that  the  underlying  lung  tissue  is  not  being 
expanded,  because  the  sounds  may  be  prevented  from  reaching  the 
ear  by  fluid  effused  into  the  pleural  cavity  (pleurisy). 

The  Changes  in  the  Intrathoracic,  Intrapuhnonic  and  Intra- 
abdominal Pressures. — It  has  previously  been  shown  that  the  recoil 
of  the  stretched  tissue  of  the  lungs  sets  up  a  pressure  in  the  intrapleural 
and  mediastinal  spaces  which  is  negative  to  that  inside  the  respiratory 
passage.  Knowing  its  cause,  it  may  justly  be  assumed  that  the  in- 
spiratory enlargement  of  the  chest  increases  this  negativity  still 
further,  because  the  lungs  are  subjected  to  a  somewhat  greater  elastic 
tension  during  this  period.  The  expiratory  movement,  on  the  other 
hand,  diminishes  the  elastic  pull  of  these  organs,  and  hence,  also  the 
intrathoracic  pressure,  i.e.,  it  permits  the  pressure  to  approach  that  of 
the  atmospheric  air  or  zero-line.  These  changes  may  be  followed 
more  closely  by  connecting  the  intrapleural  space  with  a  water  man- 
ometer in  the  manner  previously  described.  With  the  chest  in  the 
static  position  the  intrapleural  pressure  amounts  to  about  —5  mm. 
Hg,  i.e.,  to  760  mm.  Hg  atmospheric  pressure  minus  5  mm.  Hg  produced 


478 


RESPIRATION 


by  the  elastic  recoil  of  the  lung  tissue,  which  equals  755  mm.  Hg. 
During  quiet  inspiration  it  attains  a  value  of  —9  mm.  Hg  and  daring 
forced  inspiration  a  value  of  as  much  as  —30  or  —40  mm.  Hg. 

The  intrapuhnonic  pressure  pursues  a  similar  course.  It  falls 
during  inspiration  and  rises  during  expiration,  but  remains  always 
above  the  former.  As  the  chest  is  expanded,  the  pressure  in  the  pul- 
monary^ passage  falls  below^  that  of  the  air  without,  initiating  a  rapid 
inflow  of  air  which  does  not  cease  until  an  equalization  has  been  ef- 
fected. Quite  similarly,  the  expiratory  movement  places  the  air  in 
the  respiratory  passage  under  a  pressure  higher  than  that  of  the  at- 
mosphere, and  gives  rise  to  an  outflow  of  air  which  does  not  cease  until 
the  pressures  have  been  equalized.  It  need  scarcely  be  mentioned  that 
the  cause  of  these  changes  in  the  intrapulmonic  pressure  is  to  be  sought 
in  the  resistance  encountered  by  the  air  in  its  passage  through  the 
relatively  narrow  tracheal  communication,  and  especially  in  its  flow 


<-  Inspiratiof?.  -» 
760m7?i. 

-£i^2.2---'^  <:- Expiration.-^ 

7S8 

A.  Intra-pulmonic  Pressure. 

760  mm  "^  ^"■^pi^'^^i^^^^-  -'>^- Expiration 


7S1 

B.  Intra-thoracic  Pressure. 

Fig.  247. — Representing  the  Changes,  1,  in  the  iNTRAPtrLMONic,  and  2,  in  the  Intra- 
thoracic Pressure  During  Inspiration  and  Expiration. 

through  the  glottis.  Quite  naturally,  any  condition  which  lessens 
the  lamen  of  the  upper  portion  of  the  respiratory  passage,  must  tend 
to  augment  these  variations  in  the  intrapulmonic  pressure.  It  must 
also  be  evident  that  these  changes  may  be  intensified  by  breathing 
more  forcibly.  Under  ordinarv'  conditions,  however,  the  inspiratory 
fall  in  intrapulmonic  pressure  amounts  to  only  1.5  mm.  Hg,  while  its 
expiratoiy  rise  rareh"  exceeds  2.5  to  3  mm.  Hg.  During  forced  respi- 
ration much  higher  values  are  obtained.  Donders,  for  example,  was 
able  to  cause  a  fall  of  57  mm.  Hg  and  a  rise  of  87  mm.  Hg,  the  pressure 
being  registered  in  this  case  by  a  manometer  which  was  connected 
with  one  nostril,  while  the  other  was  held  shut. 

The  intra-ahdo?7nnal  pressure  is  registered  by  inserting  a  hollow 
probe  among  the  superficial  coils  of  intestine  and  connecting  its  free 
end  with  a  water  manometer.  During  quiet  respiration  it  retains 
a  value  very  close  to  zero,^  but  naturally,  the  active  participation  of 

^  Emerson,  Archiv  of  Int.  Medicine,  vii,  1911,  1. 


FREQUENCY  AND  CHARACTER  OF  RESPIRATORY  MOVEMENTS      479 


the  al)doniinal  muscles  in  expiration  pives  rise  to  much  higher  values. 
This  is  also  true  of  those  expiratory  blasts  of  air  which  are  made  use 
of  in  speaking,  singing,  coughing,  and  sneezing.  Inasmuch  as  the  peri- 
toneal cavity  cont^iins  no  air,  the  individual  organs  are  packed  closely 
together.  By  closing  the  glottis  and  simultaneously  contracting  the 
diaphragm  and  abdominal  muscles,  they  may  be  subjected  to  a  con- 
siderable pressure,  which  greatly  aids  in  the  expulsion  of  the  feces  and 
ui'ine.  Tiiis  action,  which  is  commonly 
designated  as  the  "abdominal  press,"  also 
constitutes  an  important  factor  in  child- 
birth. 

Quantitative  Determination  of  the 
Respired  Air. — The  volume  of  air  which 
is  taken  into  our  lungs  during  a  given 
period  of  time,  varies  with  the  respiratory 
needs  of  our  body.  Obviously,  a  much 
greater  quantity  of  air  is  required  when 
the  tissues  are  active  than  when  they  are 
inactive.  But  while  the  extent  and  fre- 
quency of  the  respiratory  movements 
may  serve  at  any  time  as  an  indication 
of  the  intensity  of  the  gas  interchange,  a 
direct  volumetric  determination  of  the 
air  respired  is  only  possible  by  calibration. 
The  instrument  used  for  this  purpose  is 
known  as  the  spirometer.  The  one  de- 
vised by  Hutchinson'  is  a  modified  gaso- 
meter (Fig.  248).  It  consists  of  a  cylin- 
drical receptacle  (B)  filled  with  water,  in 
which  is  suspended  a  second  cyhnder  (A) 
containing  air.  The  latter  is  counter- 
balanced by  weights  (G)  in  such  a  manner 
that  it  may  be  made  to  move  with  the 
least  possible  resistance.  The  tube  (C) 
enters  through  the  outside  cylinder,  and  is 
continued  upward  to  a  level  above  the 
surface  of  the  water  in  the  inside  com- 
partment. If  air  is  expired  through  this 
tube,  the  inside  cylinder  rises  a  certain  distance  out  of  the  water, 
while  if  air  is  inspired  through  it,  the  cylinder  sinks  to  a  lower  level. 
The  amounts  of  air  added  or  subtracted  in  this  way  are  indicated 
by  a  pointer  upon  a  neighboring  centimeter  scale. 

In  order  to  be  able  to  determine  the  volume  of  the  air  breathed  in 
the  course  of  a  long  period  of  time,  it  is  necessary  to  know  two  factors, 
namely,  the  average  frequency  of  the  respirator}^  movements  and  the 
average  volume  of  air  respired  each  time.     It  is  also  possible  to  solve 

1  Med.-chirurg.  transact.,  xxix,  1846,  137. 


Fig.  24^. — \\'intrich'.s  Modi- 
fication OF  HUTCHIXSOX'S  SPIRO- 
METER.     (Reichert.) 


480  RESPIRATION 

this  problem  with  the  help  of  Gad's  pneumatograph^  which  consists 
of  a  square  box  with  double  walls,  the  space  between  them  being  filled 
with  water  (Fig.  249).  The  cover  of  this  air-chamber  is  fastened 
with  hinges  on  one  side,  but  is  freely  movable  along  its  other  three 
sides.  If  air  is  breathed  from  or  into  its  central  compartment,  the 
cover  moves  down  or  up,  its  excursions  being  registered  upon  the  paper 
of  a  slowly  revolving  kymograph. 

Quantities  of  Air  Respired. — A  full  grown  man  inspires  and  expires 
about  500  c.c.  of  air  with  each  respiratory  act,  the  expiratory  volume 
being  slightly  larger  on  account  of  its  expansion  by  heat.  This  is 
called  the  tidal  air.  By  the  deepest  possible  inspiration  an  additional 
quantity  may  be  accommodated  which  amounts  to  at  least  1600  c.c. 
This  is  the  compleniental  air.  Quite  similarl}',  the  most  forcible 
expiration  relieves  the  lungs  of  about  1600  c.c.  of  air  in  addition  to 
the  500  c.c.  of  tidal  air.     This  amount  is  designated  as  the  supple' 


lio.   Ui'j. — Gad's   VsKvyviiouii-WU. 

mental  air.  It  is  to  be  noted,  however,  that  even  the  most  forcible 
expiratory  effort  does  not  empty  the  lungs  completely.  A  certain 
quantity  is  always  left  behind,  because  the  lungs  do  not  collapse 
even  during  forced  expiration,  but  remain  in  a  condition  of  partial 
distention.  This  air,  which  cannot  be  expelled  normally,  is  the  residual 
air.  Its  amount  has  been  estimated  at  1000  to  1200  c.c.^  Its  func- 
tion, obviously,  is  to  prevent  the  alveolar  walls  from  collapsing,  because 
in  this  eventuality  very  much  greater  muscular  efforts  would  be  re- 
quired to  subject  these  cells  again  to  a  normal  degree  of  inspirator}'  dis- 
tention. Furthermore,  it  must  be  evident  that  this  partially  expanded 
condition  of  the  lungs  favors  a  free  movement  of  the  blood  through  the 
pulmonary  capillaries.  In  this  connection  brief  reference  should  also 
be  made  to  the  fact  that  the  residual  air  cannot  be  removed  in  its 
entirety  even  by  opening  the  thorax  and  by  permitting  the  lungs  to 
collapse.  Neither  can  this  end  be  attained  by  exerting  a  gentle 
pressure  upon  the  surfaces  of  the  excised  organ,  because  the  walls 

1  Archiv  fiir  Anat.  und  Physiol.,  1879,  181.  Modifications  of  this  spirometer 
have  been  constructed  by  Durig  (ZentralVjl.  fiir  Physiol.,  xvii,  1904,  2.5Sj,  Gutz- 
mann  (^lediz.  KUnik,  1910),  and  Zwaardemaker  (Archiv  intern,  de  laryngologie, 
1906). 

2  Jacobson,  Pfliiger's  Archiv,  xUii,  1888,  236. 


FREQUENCY   AND   CHAHACTElt   OF  ItESPIltATOKY   MOVEMENTS       481 

of  the  small  bronchial  tubules  iiave  como  tofrcdu'r  before  the  iu- 
fuiulibula  have  been  completely  emptied.  In  this  way  a  portion 
of  the  residual  air  has  been  entrapped  in  the  different  air  cells.  This 
constitutes  the  minimal  air.  It  is  possible  to  remove  it,  however  by 
chemical  means;  for  exami)le,  l)y  displacing  it  with  oxyjijen  and  cari)on 
dioxid  antl  bringing  it  in  contact  with  water.  A  lung  so  treated  ceases 
to  float. 

From  the  foregoing  discussion  it  may  readily  be  gathered  that  the 
reserve  amount  of  air  which  is  contained  m  tlu;  lungs  at  the  end  of  a 
quiet  ex]nration,  following  a  quiet  inspiration,  amounts  to  al)out 
2500  c.c.  and  consists  of  the  residual  and  supplemental  portions. 
It  is  designated  as  the  stationary  air.  The  term  vital  or  respiratory 
capacity  signifies  the  quantity  of  air  which  may  be  expelled  from  the 
lungs  by  the  most  forcible  expiration  after  the  deepest  possible  in- 
spiration. It  includes  the  tidal,  complcmental  and  supplemental  por- 
tions and  may,  therefore,  be  estimated  at  3700  to  4000  c.c.  If  to  this 
quantity  is  added  the  residual  air,  the  lung  capacity  is  obtained,  which 
in  round  numbers  may  be  said  to  equal  5000  c.c.  The  term  bronchial 
capacity  refers  to  the  quantity  of  air  which  is  accommodated  in  the 
trachea  and  bronchi.  It  is  generally  estimated  at  140  c.c.  so  that  only 
360  c.c.  of  the  500  c.c.  of  tidal  air  are  actually  forced  into  the  deeper 
passages  of  the  lungs.  ^  What  bearing  this  fact  possesses  upon  the 
interchange  of  the  gases  will  be  seen  later.  While  it  is  true  that  these 
figures  allow  us  to  draw  definite  conclusions  regarding  the  respiratory 
power  of  an  individual,  no  special  clinical  value  can  be  attached  to 
them,  because  they  may  be  materially  increased  by  practice  and  are 
subject  to  a  number  of  conditions,  such  as  posture,  age,  sex,  race, 
and  occupation.  Mountaineers,  for  example,  possess  a  greater 
respiratory  capacity  than  the  inhabitants  of  lowdands. 

These  data  now  permit  us  to  compute  the  quantity  of  air  respired 
by  an  adult  person  during  a  given  period  of  time.  Assuming  that  the 
respiratory  frequency  is  15  in  a  minute  and  that  the  tidal  air  amounts 
to  500  c.c,  then  7.5  liters  are  breathed  in  a  minute,  450  liters  in  an 
hour,  and  more  than  10,000  liters  in  the  course  of  a  day.  It  is  from 
this  enormous  quantity  of  air  that  the  oxj'-gen  requirement  of  our 
tissues  is  satisfied. 

Modified  Respiratory  Movements. — The  rhythmical  enlargement 
of  the  thorax  has  as  its  object  the  ventilation  of  the  lungs  so  that  a 
proper  interchange  of  the  gases  may  be  had  between  the  intrapulmonic 
air  and  the  blood.  Under  certain  conditions,  however,  the  respiratory 
current  of  air  is  employed  during  brief  periods  of  time  for  other  pur- 
poses, this  change  generally  necessitating  a  modification  of  either 
the  inspiratory  or  expiratory  movement.  Acts  of  this  kind  are  speaking, 
singing,  coughing,  sneezing,  sighing,  laughing,  crying,  sobbing,  hic- 
cough, yawning,  and  snoring;  in  fact,  if  other  species  of  animals  are 
here  taken  into  consideration,  this  list  may  be  made  to   include   a 

1  Loewy,  Pflliger's  Archiv,  Iviii,  1894,  416. 
31 

f 


482 


RESPIRATION 


great  number  of  noises  and  sounds,  such  as  barking,  neighing,  purring, 
roaring,  bellowing,  bawling,  whining,  braying  and  growling. 

Some  of  these  reactions  are  voluntary  in  their  nature,  others  involuntary; 
furthermore,  while  some  of  them  are  undertaken  in  consequence  of  a  definite 
mental  concept,  others  lack  a  central  cause  and  are  reflex  in  their  character.  In 
many  cases  the  latter  do  not  possess  a  local  cause,  but  are  the  result  of  irritations 
in  other  parts  of  the  body.  Thus,  coughing  frequently  arises  from  inflammatory 
reactions  in  the  intestines,  stomach,  liver,  ovaries  or  uterus,  while  hiccough  is 
commonly  associated  with  irritations  in  the  stomach,  liver  or  nerve  centers.  Being 
reflex  in  their  character,  it  is  possible  at  times  to  inhibit  these  reactions  by  setting 
up  simultaneous  afferent  impulses.  Sneezing,  for  example,  may  be  prevented  by 
firmly  pressing  the  finger  upon  the  upper  lip,  while  the  act  of  yawning  may  be 
inhibited  by  a  sudden  cutaneous  stimulus. 

As  far  as  the  respiratory  movements  are  concerned,  coughing  may  be  defined 
as  an  interrupted  expiration,  the  interruption  being  due  to  the  partial  closure  of  the 
glottis.  But,  in  order  that  its  purpose  may  be  achieved,  which,  obviously,  is  the 
dislodgment  of  the  irritating  body  from  the  respiratory  passage,  it  is  necessary 
to  have  an  adequate  supply  of  air  on  hand.  For  this  reason,  this  action  is  commonly 
preceded  by  an  inspiration.  The  air  is  then  ejected  through  the  mouth,  the  glottis 
being  forced  open  by  the  abrupt  compression  of  the  intrapulmonic  air  in  consequence 
of  the  contraction  of  the  accessory  muscles  of  expiration.  Sneezing  is  accomplished 
in  practically  the  same  manner.  In  this  particular  case,  however,  the  expiratory 
blast'  of  air  is  forced  through  the  nasal  cavity,  the  glottis  being  widely  opened, 
while  the  cavity  of  the  mouth  is  shut  off  from  that  of  the  pharynx  by  the  appro.xi- 
mation  of  the  base  of  the  tongue  to  the  soft  palate.  This  act  is  also  initiated  by  a 
deep  inspiration.  Sighing  is  a  deep  and  prolonged  inspiration.  Brief,  jerky 
inspiratory  efforts,  made  with  the  mouth  closed,  constitute  the  act  of  sniffing. 
If  the  mouth  and  glottis  are  kept  open,  while  the  vocal  cords  are  thrown  into  vibra- 
tion by  an  expiratory  blast  which  is  repeatedly  interrupted,  the  phenomenon  of 
laughing  results.  Crying  is  differentiated  from  laughing  by  the  rhythm  of  the 
movement  and  the  position  of  the  facial  parts.  Sobbing  consists  of  a  series  of 
spasmodic  inspirations,  with  partially  closed  glottis,  which  are  followed  by  a 
prolonged  expiration.  Hiccough  is  produced  by  the  spasmodic  contraction  of  the 
diaphragm,  the  inspiratory  motion  being  suddenly  arrested  by  the  closure  of  the 
glottis.  In  yaioning  a  deep  inspiration  is  taken  with  the  mouth  and  glottis  widely 
open;  the  succeeding  expiration  is  short.  Snoring  results  if  the  relaxed  uvula 
and  soft  palate  are  thrown  into  vibration  by  the  inflowing  and  outflowing  air. 

Artificial  Respiration. — Conditions  arise  at  times  when  it  becomes 
necessary  to  maintain  an  adequate  ventilation  of  the  lungs  by  arti- 
ficial means.  The  methods  then  commonly  practised  may  be  divided 
into  two  groups,  namely,  those  devised  to  expand  the  lungs  from  with- 
out, as  in  normal  breathing,  and  those  effecting  their  rhythmic  in- 
flation through  the  trachea  by  air  held  under  pressure.  Artificial 
respiration  is  resorted  to  very  frequently  during  laboratory  experi- 
ments in  order  to  allow  us  to  open  the  chest  without  actually  destroying 
the  life  of  the  animal.  In  other  cases,  it  becomes  imperative  to  venti- 
late the  lungs  artificially  until  the  cause  of  the  respiratory  stoppage 
has  been  removed.  For  example,  if  an  overdose  of  ether  has  been 
given,  the  prompt  employment  of  artificial  respiration  generally 
serves  to  tide  the  animal  over  this  period,  because  in  most  instances 
the  heart  does  not  cease  to  act  until  sometime  after  the  stoppage  of 
respiration.     In  fact,  if  this  organ  has  already  ceased  to  beat,  it  may 


FREQUENCY   AND   CHARACTER   OF  RESPIRATORY   MOVEMENTS       483 

at  times  bo  reactivated  by  the  prompt  institution  of  artificial  respira- 
tion, massage  of  the  abdominal  viscera  and  central  blood-vc^ssels, 
elevation  of  the  posterior  extremities,  injections  of  adrenalin  and  other 
measures. 

In  animal  experimentation  artificial  respiration  meets  with  prac- 
tically no  difficulties,  although  its  use  upon  human  beings  must  neces- 
sarily remain  restricted  to  the  most  favorable  cases.  Thus,  it  can- 
not yield  beneficial  results  if  the  respiratory  abeyance  possesses  a  per- 
manent pathological  cause.  Still,  it  cannot  be  doubted  that  it  deserves 
a  much  wider  application  than  is  accorded  it  at  the  present  time, 
when  it  is  employed,  and  not  always  in  a  very  scientific  and  efficient 
manner,  in  cases  of  drowning,  asphyxiation  by  poisonous  gases,  and 
suspended  animation  from  electrical  shocks  or  pressure  upon  nerve 


Fig.  250. — Shows  the  Positiox  to  be  Adopted  for  Effecting  Artificial  Respiration 
IN  Cases  of  Drowning.     (Schaefer.) 

centers.  Whatever  the  method  employed,  and  whether  in  animals  or 
man,  artificial  respiration  must  always  be  practised  in  closest  imitation 
of  the  normal  rate  and  depth  of  the  respiratory  movements.  Too 
vivid  a  ventilation  is  almost  as  injurious  as  a  subnormal  one.  Before 
the  attempt  is  made  to  distend  the  lungs,  the  respiratory  passage  must 
be  cleared  of  all  obstructions,  such  as  mucus  and  water.  The  mouth 
must  be  opened  widely  and  the  tongue  drawn  out  so  as  to  prevent  its 
tip  from  becoming  lodged  behind  the  fauces.  All  tight  clothing  must 
be  removed. 

In  imitating  the  normal  expansion  of  the  lungs,  Sylvester  proceeds 
as  follows:  The  patient  is  placed  on  his  back,  with  the  head  and 
shoulders  supported  upon  a  firm  cushion  somewhat  above  the  level 
of  the  feet.  The  operator  places  himself  at  the  patient's  head,  grasps 
the  arms  just  above  the  elbows  and  draws  them  upward  above  the 
head.  Having  kept  them  in  this  position  for  two  seconds,  they  are  then 
pressed  gently  but  firmly  against  the  sides  of  the  chest  during  an  equal 
period  of  time.  Galliano  retains  the  arms  in  Sjdvester's  position, 
so  that  the  thorax  remains  in  the  expanded  condition  continuously. 
He  then  presses  at  intervals  of  three  seconds  with  the  flat  hands 


484  RESPIRATION 

against  the  sides  of  the  thorax  and  epigastric  region.  This  procedure 
may  also  be  followed  if  the  patient  is  placed  in  the  supine  position  with 
his  arms  resting  against  the  sides  of  his  body.  A  method,  which  is 
commonly  employed  in  the  resuscitation  of  animals  is  the  following: 
The  body  is  raised  free  from  the  floor  by  the  hind  limbs.  The  mouth 
is  opened  and  the  tongue  pulled  out  sjmchronouslj' with  the  compression 
of  the  thorax  which  is  effected  by  placing  the  flat  hands  from  behind 
upon  the  sides  of  the  lower  part  of  the  chest.  Schafer^  suggests  that 
the  patient  be  placed  in  the  prone  posture,  a  heav}-  gannent  being 
placed  underneath  his  chest  and  epigastrium.  The  operator  assumes 
a  kneeling  position  beside  the  legs  of  the  patient  and,  bending  forward, 
rests  his  flat  hands  against  the  sides  of  the  lower  part  of  the  thorax, 
so  that  the  tips  of  his  thumbs  come  to  he  close  to  the  vertebral  column. 
B}'  gradually  permitting  his  weight  to  be  supported  bj^  his  arms,  the 
chest  is  pressed  upon  and  air  is  forced  out  of  the  lungs.  On  releasing 
this  pressure,  the  parts  return  into  their  original  positions  and  cause 
the  air  to  flow  in. 

The  methods  which  purpose  to  distend  the  lungs  with  air  held  under 
pressure,  are  most  commonh'  employed  in  long-continued  experiments 
upon  animals,  but  may  also  be  used  in  resuscitating  human  beings. 
Thus,  the  expansion  of  the  lungs  of  the  new-born  may  be  frequently 
facilitated  by  blowing  air  into  these  organs,  the  mouth  of  the  operator 
being  placed  against  that  of  the  infant.  In  the  laboratoiy,  it  is  cus- 
tomarj'  to  expose  the  trachea  of  the  animal  and  to  insert  in  it  a  rectangu- 
lar cannula  which  in  turn  is  connected  with  a  pair  of  bellows.  In 
experiments  of  longer  duration  it  is  advantageous  to  employ  a  power 
pump  which  it  is  possible  to  regulate  in  such  a  way  that  a  different 
rate  and  amplitude  of  respiration  may  be  obtained  within  a  fe^-  mo- 
ments. The  deflation  of  the  lungs  may  be  greatly  hastened  by  the 
withdrawal  of  the  air  by  sUght  suction. ^ 

This  principle  is  made  use  of  in  the  construction  of  the  so-called 
pulmotor  or  lungmotor,^  a  small  force-pump  intended  to  be  employed 
upon  human  beings.  It  is  worked  by  hand  and  possesses  safeguards 
in  the  form  of  adjustable  valves.  It  may  readilj-  be  sm-mised  that  the 
method  of  inflation  through  the  mouth  cannot  present  any  unusual 
difficulties  in  unconscious  persons,  but  is  not  easily  execvited  when 
consciousness  has  again  been  established,  because  the  current  of  air 
is  then  stronglj^  opposed  by  the  voluntary'  muscles  in  the  region  of 
the  glottis,  and  may  in  addition  be  counteracted  by  those  of  the  thorax. 
By  endeavoring  to  overcome  this  resistance  serious  injury  may  be  in- 
flicted upon  the  lung  tissue,  but  the  conscious  subject  may  overcome 
these  reflexes  by  remaining  passive  and  by  making  inspiratoiy  move- 
ments in  unison  with  the  ingoing  blast  of  air.     Tracheotomj-  obviates 

1  .Tour,  of  the  Amer.  Jvled.  Assoc,  li,  1908,  801. 

^  A  most  satisfactory  respiration  machine  has  been  described  by  Hoj't,  Jour, 
of  Physiol.,  xxvii,  1901, "48. 

^  Henderson,  Jour.  Am.  Med.  Assoc,  Ixvii,  1916,  1. 


FREQUENCY  AND   CHARACTER  OF  RESPIRATORY  MOVEMENTS      485 

this  difficulty  in  some  measure,  but  this  procedure  cannot  be  resorted 
to  in  liuman  beings  unless  undertaken  as  a  last  means  to  save  life. 
The  manual  method  of  artificial  respiration  possesses  the  advan- 
tage that  it  can  be  applied  almost  immediately.  A  delay  of  more 
than  ten  minutes  should  never  result,  because  it  is  practically  impossi- 
ble to  restore  life  if  this  period  of  time  is  exceeded.  Furthermore,  it 
is  to  be  remembered  that  the  body  becomes  entirely  flaccid  in  the 


Fig  251  —Device  to  Illustrate  the  Influence  of  the  Respiratory  Movements 
UPON  the  Flow  of  the  Blood  through  the  Pulmonary  Blood-vessels.  {Henng.) 
A  bell  iar-  B,  rubber  membrane  closing  it;  V,  soft  rubber  pouch  to  imitate  the 
pulm.'  blood-vessels;  GH,  arrangement  for  forcing  water  through  F  under  a  constant 
pressure;  j,  manometer  connected  with  "intrapleural  space."  On  inspiration  pro- 
duced by  moving  the  rubber  membrane  downward,  the  i^trapleura  pressure  is  de- 
creased This  gives  rise  to  an  aspiration  which  tends  to  pull  the  wall  of  V  outward, 
facilitating  the  flow  from  G  to  H. 

course  of  ten  or  fifteen  minutes,  ^  and  that  it  is  then  practically  impos- 
sible to  ventilate  the  lungs  by  means  of  pressure  with  the  hands.  Res- 
piration not  having  been  restored  within  this  time,  it  is  advisable 
to  resort  to  the  method  of  inflation,  but  the  apparatus  should  be  placed 
in  the  hands  of  a  thoroughly  experienced  operator.  ^ 

It  is  a  well-known  fact  that  the  arterial  blood  pressure  rises  during 
inspiration  and  falls  during  expiration,  while  the  venous  pressure  rises 

1  LUjestrand,  Wollin  and  Nilsson,  Skand.  Archiv  fiir  Physiol.,  xxix,  1913,  198. 


486  RESPIRATION 

during  the  latter  and  falls  during  the  former  period.  These  changes, 
which  are  commonly  referred  to  as  the  respiratory  variations  in  blood 
pressure,  are  reversed  during  inflation.  It  is  easily  conceived  that 
the  establishment  of  a  positive  pressure  in  the  pulmonary  pas- 
sages, corresponding  to  the  normal  inspiratory  motion,  must  tend  to 
compress  the  pulmonary  capillaries,  thereby  producing  a  stagnation  in 
the  venous  channels  and  right  side  of  the  heart  and  a  deficiency  in 
its  left  side  and  arterial  outlets.  Just  the  opposite  effect  is  produced 
during  the  period  of  deflation.  Inasmuch  as  the  pressure  is  now 
removed  from  the  alveolar  walls,  the  pulmonary  blood-bed  must  be 
enlarged,  allowing  a  greater  quantity  of  blood  to  reach  the  arteries. 
For  this  reason,  we  obtain  an  inspiratory  fall  in  arterial  pressure  and 
an  expiratory  rise,  while,  on  the  venous  side,  the  pressure  rises  during 
inflation  and  falls  during  deflation. 

The  methods  of  artificial  respiration  previously  enumerated  are 
intended  to  effect  either  a  rhythmic  expansion  or  a  rhythmic  infla- 
tion of  the  lungs.  But  it  should  not  be  forgotten  that  these  organs 
may  also  be  retained  in  a  distended  condition  by  the  procedure  of 
constant  insufflation.^  A  long  rectangular  piece  of  tubing  is  inserted 
through  the  larynx  until  its  free  end  comes  to  lie  at  the  bifurcation 
of  the  bronchi.  A  steady  stream  of  air  is  then  permitted  to  flow 
through  this  tube  until  the  thorax  assumes  a  position  of  moderate 
distention.  Care  must  be  exercised,  however,  that  the  outflow  of 
air  along  the  sides  of  this  tube  be  not  hindered  in  any  way,  because 
an  excessive  positive  pressure  gives  rise  to  an  immediate  fall  in  arterial 
pressure  dependent  upon  a  compression  of  the  pulmonary  capillaries. 


CHAPTER  XXXIX 
THE  CHEMISTRY  OF  RESPIRATION 

The  Character  of  the  Inspired  and  Expired  Air. — The  gaseous 
metabolism  of  the  tissues  consists,  on  the  one  hand,  in  a  constant 
acquisition  of  oxygen  and,  on  the  other,  in  an  evolution  of  carbon 
dioxid.  This  change  from  one  into  the  other  is  not  accomplished 
in  a  direct  way,  but  only  with  the  help  of  several  intermediate  reactions 
which  together  constitute  the  process  of  oxidation.  Obviously, 
the  purpose  of  these  reactions  is  the  reduction  of  the  carbon  and 
hydrogen  of  the  food  and  the  liberation  of  energy  in  its  different  forms. 
The  blood  and  lymph  serve  as  the  medium  in  which  this  assimilation 
and   dissimilation  is  effected,   while   the  lungs    enable    these    body 

1  Meltzer,  Jour.  Am.  Med.  Assoc,  Ivii,  1911,  521,  also,  Zentralbl.  fur  Physiol., 
xxvi,  1912,  161. 


THE    CHEMISTRY    OF    RESPIRATION  487 

fluids  to  oxcliange  their  gaseous  constituents  with  the  surrounding 
air.  Respiration,  therefore,  consists  of  two  processes,  namely,  an 
interchang(>  between  the  outsider  air  and  the  blood  and  an  interchange 
between  tiie  latter  and  the  cellular  components  of  the  tissu(;s.  The 
former  process  is  known  as  external  respiration  and  the  latter,  as  in- 
ternal respiration. 

The  fact  that  the  general  metabolism  of  an  animal  necessitates 
an  intake  of  oxygen  and  an  outgo  of  carbon  dioxid  may  readily  be 
gathered  from  a  comparison  of  the  chemical  and  physical  character- 
istics of  inspired  and  expired  air.  Concerning  the  former,  it  should 
chiefly  be  remembered  that  the  inspired  air  contains  more  oxygen 
and  less  car]>on  dioxid  than  the  expired.  The  figures  in  volume  per 
cent,  generally  given  arc  the  following: 

N  O  CO2 

Inspired  air 79.00         20.96         0.04 

Expired  air 79.50         16.02         4.10 


4.94         4.06 

Argon,  krypton  and  neon  are  not  included  in  this  table,  because 
they  have  not  been  shown* to  possess  a  definite  function.^  Besides, 
it  should  be  remembered  that  these  figures  are  subject  to  slight 
variations,  because  inasmuch  as  the  composition  of  the  inspiratory 
air  differs  somewhat  in  different  localities,  the  expiratory  air  must 
present  very  similar  fluctuations.  In  addition,  the  latter  exhibits 
certain  minor  changes  which  are  caused  by  periodic  variations  in  the 
depth  of  the  respiratory  movements  and  intensity  of  the  tissue  metab- 
olism. In  general,  however,  it  may  be  said  that  the  air  loses  during 
its  sojourn  in  the  lungs  4.94  volumes  of  oxygen  and  gains  4.34  volumes 
of  carbon  dioxid.     Its  content  in  nitrogen  remains  practically  the  same. 

These  analyses  also  show  that  the  volume  of  oxygen  retained  is 
larger  than  the  volume  of  carbon  dioxid  given  off,  which  fact  seems 
to  indicate  that  a  fractional  amount  of  the  former  gas  is  excreted  as 
water.  In  the  second  place,  the  constancy  of  the  nitrogen  proves  that 
it  possesses  no  respiratory  value  other  than  that  it  serves  as  the  medium 
in  which  the  diffusion  of  the  other  two  gases  is  enacted.  It  is  to  be 
noted,  however,  that  the  expired  air  generally  contains  a  slight  quantity 
of  cellular  material  which  on  analysis  tends  to  heighten  the  percentage 
amount  of  nitrogen.  In  round  figures  this  increase  is  usually  esti- 
mated at  0.4  per  cent.  The  expired  air  may  also  contain  traces  of 
hj'drogen  and  methane  which  in  all  probability  find  their  origin  in 
fermentations  in  the  intestines. 

Regarding  the  physical  characteristics  of  the  respu'ed  air,  it  is  noted 
that  the  expired  air  is  warmer  than  the  inspired ;  but  naturally,  its  actual 
temperature  varies  considerably,  because  the  temperature  of  the  in- 
spired air  fluctuates  with  the  time  of  the  year  and  the  conditions  under 
which  the  animal  is  living.     Besides,  much  depends  upon  the  rapidity 

'  Regnard  and  Schloessing,  Compt.  rend.,  cxxiv,  1897,  302. 


488  RESPIRATION 

and  depth  of  the  respiratory  movements,  the  intensity  of  the  metab- 
oHsm,  and  other  factors.  Under  ordinary  conditions,  however, 
air  of  20°  C.  is  warmed  to  the  temperature  of  the  body,  or  nearly  so, 
while,  at  lower  temperatures,  the  rise  as  such  may  be  greater  but  does 
not  reach  37°  C.  At  6.3°  C,  for  example,  the  inspired  air  is  heated  to 
29.8°  C.  The  greatest  heat  absorption  takes  place  in  the  deeper 
respiratory  channels,  while  the  difference  in  the  temperature  of  the 
outside  air  and  that  in  the  lower  portion  of  the  trachea  amounts  to 
only  a  few  degrees  centigrade.  It  is  evident,  therefore,  that  this  loss 
of  body-heat  is  effected  very  largely  through  the  l^lood  of  the  pulmonary 
circuit  and  adjoining  venous  trunks.  This  fact  is  made  use  of  in  the 
open  air  treatment  of  respiratory  diseases  for  purposes  of  lowering 
the  body-temperature.  Ordinarily,  of  course,  the  respiratory  tract 
of  man  does  not  play  an  important  part  in  heat  dissipation,  but 
some  animals,  and  especially  those  possessing  a  thick  covering  of 
hair,  are  almost  wholly  dependent  upon  this  channel  for  the  regula- 
tion of  their  body-temperature. 

In  consequence  of  this  absorption  of  heat,  the  intrapulmonic  air 
increases  in  volume  and  becomes  nearly,  saturated  with  water,  but 
if  the  necessary  corrections  are  made  for  the  temperature  and  pressure 
and  if  the  aqueous  vapor  is  driven  off,  its  volume  is  slightly  less  than 
that  of  the  inspired  air  (J-^so  part).  This  loss  is  accounted  for  by  the 
fact  that  a  small  portion  of  the  oxygen  is  not  given  off  as  cai'bon  dioxid, 
but  is  either  united  with  the  sulphur  of  the  proteins  or  is  used  in  the 
oxidation  of  the  hydrogen.  In  the  latter  case  it  reappears  as  water. 
It  will  be  seen,  therefore,  that  the  body  loses  a  certain  amount  of  its 
heat  in  the  form  of  bound  heat,  because  a  portion  of  it  is  set  aside  for 
the  purpose  of  warming  the  air  in  the  pulmonary  passages,  and  a 
portion  for  the  purpose  of  converting  the  water  into  the  gaseous  state. 
This  aqueous  vapor  in  the  expiratory  air  is  of  considerable  physiological 
importance,  because  at  37°  C.  its  tension  amounts  to  50  mm.  Hg. 
Assuming,  therefore,  that  dry  air  is  being  breathed  at  the  ordinary 
pressure  of  760  mm.  Hg,  the  tension  in  the  deeper  recesses  of  the  lungs 
would  amount  to  only  760  —  50  =  710  mm.  Hg.  Thus,  the  lungs 
serve  not  only  as  a  means  of  regulating  the  body-temperatm'e,  but 
also  as  a  means  of  adjusting  the  water  content  of  the  tissues.  The 
expired  air  is  also  prone  to  contain  extraneous  material,  consisting 
chiefly  of  fragments  of  the  lining  of  the  pulmonary  passage. 

The  Interchange  of  the  Gases  Between  the  Tidal  Air  and  the 
Blood. — It  has  previously  been  shown  that  the  quantity  of  air  shifted 
with  each  respiratory  movement  is  relatively  small,  amounting  on 
an  average  to  only  500  c.c.  For  this  reason,  it  must  be  evident  that 
only  the  outer  respiratory  passage  is  ventilated  with  each  respiration, 
while  the  air  in  the  infundibula  remains  stationary.  Consequently, 
the  interchange  of  the  gases  between  the  outside  air  and  the  blood, 
which  is  commonly  designated  as  "external"  respiration,  consists 
in  reality  of  two  processes,  namely  (a)  the  shifting  of  the  tidal  air  in 


THE    CHEMISTRY    OF    RESPIRATION  489 

mass  and  (b)  the  atomic  movement,  of  the  constituents  of  tlie  air  in  the 
deeper  recesses  of  the  Umfi;.  Thus,  we  luive,  on  tlie  one  hand,  an  alter- 
nate inward  and  outward  movement  of  definite  quantities  of  air  and, 
on  the  other,  an  atomic  interchange  of  the  gases  betwecni  the  tidal 
air  and  the  blood  directly  through  the  walls  of  the  alveoli  and  capillaries. 
The  former  is  a  movement  of  a  definite  mass  of  air  as  a  whole;  and  the 
latter,  a  progression  of  the  atoms  of  the  gases  in  accordance  with 
their  diffusion  pressures  and  other  properties. 

The  interchange  of  the  gases  between  the  tidal  air  and  the  blood 
has  been  ex])lained  in  a  physical  and  in  a  chemical  way.  The  former 
explanation,  which  is  commonly  accepted  to-day,  is  based  upon  the 
ordinary  physical  laws  of  the  diffusion  of  gases,  while  the  latter  neces- 
sitates the  assumption  that  the  cells  hning  the  alveoli  possess  a 
definite  vital  activity,  leading  to  a  secretion  of  the  gases  through  this 
membrane. 

The  fhysical  theory,  first  of  all,  recognizes  the  fact  that  the  gases 
in  the  minute  air  spaces  and  in  the  blood  are  separated  from  one 
another  by  a  permeable  membrane  formed  by  the  Hning  cells  of  the 
alveoli  and  capillaries.  If  it  is  now  assumed  that  the  partial  pressures 
of  these  gases  are  the  same  on  the  two  sides  of  this  membrane,  an 
equilibrium  must  exist  which  renders  the  diffusion  equal  in  both  direc- 
tions. But  in  as  much  as  the  body  makes  constant  use  of  the  oxj^gen 
and  yields  in  turn  carbon  dioxid,  the  region  on  the  inner  side  of  this  mem- 
brane must  give  lodgment  to  relatively  much  smaller  amounts  of  oxygen 
and  much  larger  amounts  of  carbon  dioxid  than  the  outer  region. 
Consequently,  the  partial  pressure  of  the  oxygen  in  the  blood  must  be 
consider abty  below  that  in  the  alveoli  and  adjoining  larger  air  passages, 
while  the  tension  of  the  carbon  dioxid  must  be  greater  in  the  blood. 
Obviously,  therefore,  the  atoms  of  oxygen  must  progress  from  without 
to  within,  while  the  molecules  of  carbon  dioxid  must  flow  from  within  to 
without.  Inasmuch  as  the  body  does  not  make  use  of  the  nitrogen, 
this  gas  remains  "stationary, "  and  serves  mostly  as  the  medium  for  the 
diffusion  of  the  other  two  gases.  It  should  be  remembered,  however, 
that  the  term  "stationary"  is  only  a  relative  one,  because  an  actual 
standstill  of  the  atoms  of  nitrogen,  or  of  any  other  gas,  is  not  in  accord 
with  our  modern  conception  of  the  behavior  of  gases.  Even  when 
resting,  their  atoms  move  about  constantly,  although  they  do  not  ad- 
vance in  large  numbers  in  any  one  particular  direction. 

On  further  inquiry  into  the  conditions  prevailing  in  the  intrapul- 
monic  spaces,  it  is  found  that  the  capacity  of  the  bronchial  tree  is 
only  140  c.c.  and  that  the  air  contained  therein  possesses  practically 
the  same  composition  as  the  atmospheric.  Consequenth%  the  partial 
pressure  of  the  oxygen  in  these  spaces  must  amount  to  152  mm.  Hg 
and  that  of  the  carbon  dioxid  to  practically  zero.  Keeping  these  facts 
firmly  in  mind,  let  us  see  how  great  a  partial  pressure  these  gases 
exert  in  the  alveoli  and  in  the  blood  entering  the  lungs.  These  values 
can  only  be  ascertained  by  a  chemical  analysis  of  the  air  resident 


490 


RESPIRATION 


in  the  alveoli  themselves,  because  as  the  air  from  the  deeper  recesses 
of  the  lungs  moves  outward,  it  intermingles  with  that  contained  in 
the  outer  passages,  and  gives  rise  to  a  disproportional  relationship  of 
the  gases.  For  this  reason,  an  analysis  of  ordinary  expiratory  air 
cannot  yield  exact  results.     It  is  possible,  however,  to  determine  its 

mean  oxj^gen  and  carbon  dioxid  content 
by  collecting  the  last  portions  of  the  air 
expelled  by  two  forced  expirations,  one 
of  which  follows  a  normal  inspiration 
and  the  other,  an  ordinary  expiration 
(Haldane). 

Zuntz  and  Loewy  have  calculated 
the  composition  of  alveolar  air  by  con- 
trasting the  capacity  of  the  bronchial 
tree  with  that  of  the  alveoh.  Thus,  if 
the  volume  of  the  expnatory  air  is 
reckoned  at  500  c.c,  140  c.c.  of  this 
amount  must  be  derived  from  the  bron- 
chial tree  and  360  c.c.  from  the  deeper 
recesses  of  the  lung.  Fm'thermore,  if 
the  expired  air  contains  4.38  per  cent, 
of  carbon  dioxid,  the  alveolar  air  must 
embrace  4.38  -^  ^^^-is,  or  6  per  cent,  of 
this  gas.  Actual  analyses  upon  human 
beings  have  not  yielded  absolutely  con- 
stant values,  but  show  variations  be- 
tween 11  and  17  per  cent,  of  an  atmos- 
phere for  oxygen  and  between  3.7  and 
6.2  per  cent,  of  an  atmosphere  for  carbon 
dioxid.  The  average  percentage  of 
oxygen,  therefore,  may  be  estimated  at 
14.5,  that  of  carbon  dioxid  at  5.5,  and 
that  of  nitrogen  at  80.  Thus,  it  will  be 
seen  that  the  oxygen  tension  in  alveolar 
air  amounts  to  109  mm.  Hg  and  that  of 
carbon  dioxid  to  40  mm.  Hg.  If  these 
figures  are  now  compared  with  those 
given  previously  for  the  air  in  the  bron- 
chial tree  (tidal  air),  it  is  evident  that 
the  atoms  of  oxj^gen  must  flow  from  with- 
out to  within,  and  the  molecules  of  car- 
bon dioxid  from  within  to  without. 


Fig.  252. — Diagr.\ji  to  Show 
THE  Principle  of  the  Aerotoxo- 

METER. 

A,  the  tube  containing  a  known 
mixture  of  gases,  O,  CO2,  N;  C, 
the  outside  jacket  for  maintain- 
ing a  constant  body  temperature. 
When  stopcock  6  is  open  the 
blood  trickles  down  the  sides  of  A 
and  enters  into  diffusion  relations 
with  the  contained  gases.  After 
equilibrium  is  reached  the  stop)- 
cock  b  is  closed  and  a  is  opened. 
By  means  of  the  mercury  bulb  the 
gases  can  then  be  forced  out  of  A 
into  a  suitable  receiver  for  analy- 
sis.    (Howell.) 


In  further  analysis  of  this  subject  matter  let  us  now  ascertain  whether  this 
relationship  also  prevails  between  the  alveolar  air  and  the  blood.  The  determina- 
tion of  the  tension  of  the  gases  in  the  blood  presents  several  difficulties,  because 
it  requires  the  bringing  together  of  the  latter  with  different  gases  possessing 
known  tensions,  until  one  is  found  with  which  it  is  in  equilibrium.     This  end  is 


THE    CHEMISTRY    OF    RESPIRATION 


491 


usually  accomplished  in  a  perfectly  direct  way  with  the  help  of  an  instrument 
known  as  an  aerotonometer.  The  apparatus,  devised  by  Pfli'iger,  consists  of  two 
glass  tubes  which  are  placed  in  a  receptacle  containing  water  at  37°  C.  ^  One  of 
these  is  filled  with  a  gaseous  mixture  having  a  greater  and  the  other  with  a  gaseous 
mixture  liaving  a  lesser  partial  pressure  than  is  expected  to  be  found  in  the  blood 
under  examination.  Thus,  if  it  is  our  intention  to  determine  the  tension  of  the 
COj  in  venous  l)lood,  which  may  be  estimated  at  about  4  per  cent.,  one  of  these 
tubes  is  filled  with  a  mixture  containing  3  per  cent.  CO2,  and  the  other  with  a 
mixture  containing  5  per  cent.  CO2.     On  permitting  the  blood  to  run  in  a  thin 


Fig.  253. — A,   Krogh's    Microtoxometer.     B,    Upper    Part   of    Microtonometer 
Showln'g  Capillary  Tl"be  into  Which  the  Bubble  is  Returned  for  Measurement  and 

Analysis. 


layer  down  the  walls  of  these  tubes,  it  yields  CO  2  to  one  mixture  and  abstracts  it 
from  the  other.  The  proportion  of  CO2  found  in  the  mixtures  at  the  end  of  the 
experiment,  forms  the  basis  of  the  calculation  of  the  partial  pressure  of  the  CO2 
in  the  blood,  because  this  value  corresponds  to  the  partial  pressure  which  would 
have  to  prevail  in  the  tubes  in  order  that  the  blood  be  able  to  traverse  them 
without  suffering  a  change  in  its  CO2  content. 

The  aerotonometer  of  Bohr-  embodies  the  principle  of  the  stromuhr  and 
permits  the  blood  to  reenter  the  blood-vessel  after  it  has  been  temporarily  diverted 
into  the  gas  chamber.  On  this  account,  these  determinations  may  be  continued 
for  a  much  longer  period  of  time,  allowing  a  thorough  equilibrium  to  be  established. 
Krogh'  uses  a  small  bubble  of  air  which  is  brought  into  contact  with  a  correspond- 

1  Modified  bv  Fredericq,  Zentralbl.  fur  Physiol.,  viii,  1894,  34. 

2  Skand.  Archiv  fiir  Physiol,  ii,  1900,  236. 

3  Ibid.,  XX,  1908,  279. 


492 


RESPIRATION 


ingly  small  quantity  of  blood  until  an  equilibrium  has  resulted,  which  in  this 
case  requires  a  much  shorter  time  than  by  any  of  the  procedures  mentioned  pre- 
viously. The  apparatus  itself  consists  of  a  tonometer  and  a  tubular  receptacle 
for  the  analysis  of  the  gas  bubble.  The  latter  is  first  played  upon  by  a  small  jet 
of  blood  led  in  by  a  narrow  cannula,  its  size  being  then  measured  by  drawing 
it  into  a  graduate.  The  absorption  of  carbon  dioxid  and  oxygen  is  carried  out 
in  the  usual  manner  by  using  potash  and  pyrogallic  acid. 

Another  method  frequently  employed  for  the  determination  of  the  tension  of 
the  gases  in  the  venous  blood  of  the  lungs  requires  the  use  of  a  pulmonary  catheter, i 
which  consists  of  two  tubes,  one  being  situated  within  the 
other.  The  outer  tube  is  somewhat  shorter  than  the  inner, 
and  is  closed  by  a  rubber  balloon  which  after  the  insertion 
of  the  catheter  in  the  bronchus,  is  inflated  until  it  com- 
pletely blocks  the  respiratory  passage.  Samples  of  air 
are  then  withdrawn  through  the  inner  tube  at  interv^als, 
until  the  diffusion  of  the  gases  between  the  alveoli  and  the 
blood  has  continued  long  enough  to  establish  an  equili- 
brium. Haldane  and  Smitlj-  have  estimated  the  oxygen 
tension  in  the  arterial  blood  in  tlie  following  manner: 
The  subject  is  permitted  to  breathe  known  quantities  of 
carbon  monoxid  until  the  hemoglobin  has  combined  with 
as  much  of  this  gas  as  it  will  acquire.  The  percentage 
amount  of  this  gas  in  the  hemoglobin  is  then  ascertained 
in  a  sample  of  blood  taken  either  from  the  finger  or  from 
the  lobule  of  the  ear.  Eventually,  when  the  absorption 
of  carbon  monoxid  has  ceased,  its  tension  in  the  aerated 
blood  of  the  lungs  will  be  the  same  as  that  in  the  inspired 
air.  The  latter  value,  as  well  as  the  extent  to  which  the 
hemoglobin  has  been  saturated  with  carbon  monoxid, 
being  known,  the  tension  of  the  oxj'gen  in  the  blood  leaving 
the  lungs  is  also  known. 

While  the  values  obtained  with  these  methods 
show  considerable  fluctuations,  it  may  safely  be 
concluded  that  the  tension  of  the  gases  in  the 
arterial  blood  closely  coincides  with  that  of  the 
corresponding  gases  in  the  alveolar  air.  To  be 
exact,  the  carbon  dioxid  of  the  alveoli  is  always 
under  a  slightly  lower  pressure  than  that  of  the 
blood,  while  the  oxygen  is  under  a  slightly  higher 
pressure.  In  the  latter  case,  the  difference  amounts 
to  1-4  per  cent,  of  an  atmosphere;  moreover,  it  has 
been  shown  by  Krogh  to  persist  even  if  the  com- 
position of  the  alveolar  air  is  altered  artificially. 
That  is  to  say,  while  any  change  in  the  tension  of 
the  constituents  of  the  alveolar  air  is  immediately  followed  by  a  cor- 
responding alteration  in  the  tension  of  the  gases  in  the  blood,  the 
oxygen  pressure  is  always  greater  in  the  alveoli  than  in  the  blood, 
whereas  the  carbon  dioxid  tension  is  higher  in  the  blood  than  in  the 
alveoli. 

Much  greater  differences  have  been  ascertained  in  the  venous 

1  Loewy  and  Schrotter,  Zeitschr.  fiir  exp.  Pathol,  und  Therapie,  i,  1905,  197. 

2  Jour,  of  Physiol.,  xxii,  1897,  231. 


Fig.  2  5  4.— Dia- 
gram Illustrating  the 
Diffusion  of  the 
Gases  Between  the 
Tidal  Air  and  the 
Blood. 

r,  trachea;  TA, 
tidal  air;  B,  bronchi; 
/,  infundibulum;  C, 
capillaries;  O,  oxygen 
atoms;  CO2,  molecules 
of  carbon  dioxid. 


THE    CHEMISTRY    OF    liESPIHATION 


493 


blood  leaving  tho  hoart,  in  wliioh  the  tension  of  the  oxygen  is  5.3  p(!r 
cent.  =  37. ()  mm.  Ilg  and  that  of  carbon  dioxid  (i  per  cent.  =  40  mm. 
Hg.  If  these  values  are  now  contrasted  with  those  previously  given 
for  the  alveolar  air,  it  is  evident  that  the  difference  in  the  tension  of 
the  oxygen  amounts  to  109  —  37,  or  72  mm.  Hg,  and  that  of  the  carljon 
dioxid  to  46  —  40,  or  (3  mm.  Hg.  Consequently,  the  difference  in  the 
tension  of  the  oxygen  on  the  two  sides  of  the  limiting  membrane  is 
much  greater  than  that  of  the  carbon  dioxid ;  in  either  case,  however, 
it  must  be  clear  that  the  atoms  of  oxygen  flow  into  the  blood  and  the 
molecules  of  carbon  dioxitl  into  the  alveoli. 


Oxygen, 
mm.  Hg 

Carbon  dioxid, 
mm.  Hg 

Atmospheric  air 

152 
109 

i 

00 

Alveolar  air 

40 

Membrane 

T 

Venous  blood 

37 

46 

Under  normal  conditions  the  lining  cells  of  the  alveoli  and  cap- 
illaries offer  no  hindrance  to  the  passage  of  these  gases,  the  difference  in 
their  partial  pressures  being  sufficient  to  cause  them  to  move  in  these 
directions.  At  times,  however,  the  orderly  flow  of  the  gases  may  be 
greatly  impaired  by  infiltrations  of  the  lining  cells  or  by  serous  mate- 
rial exuded  into  the  alveolar  spaces  in  consequence  of  inflammatory 
processes  (pneumonia).  As  may  readily  be  gathered,  this  difficulty 
can  be  overcome  in  a  measure  by  increasing  the  driving  force  behind 
the  atoms  of  oxygen.  With  this  point  in  view,  pure  oxygen  is  some- 
times substituted  for  the  atmospheric  air,  the  intention  being  to  in- 
crease the  partial  pressure  of  this  gas  so  that  at  least  a  part  of  it  will 
be  driven  into  the  system.  Obviously,  pure  oxygen  possesses  a 
partial  pressure  five  times  greater  than  that  of  the  oxygen  in  atmos- 
pheric air. 

Under  normal  conditions,  however,  the  diffusion  of  the  gases  in 
the  lungs  is  amply  protected,  owing  to  the  enormous  expanse  of  the 
respiratory  surface.  Upon  the  basis  of  700,000,000  alveoli,  possessing 
an  average  diameter  of  0.2  mm.,  Zuntz^  has  estimated  that  the  3000  c.c. 
of  stationary  air  are  in  relation  with  900,000  sq.  cm.  or  90  sq.  m.  of 
surface.^  Thus,  it  will  be  seen  that  each  square  centimeter  of  alveolar 
surface  is  required  to  supply  only  0.0003  c.c.  of  carbon  dioxid  in  a  min- 
ute, the  total  diffusion  of  this  gas  in  this  period  of  time  being  calculated 
at  300  c.c,  namely,  at  500  c.c.  of  tidal  air  X  0.04  per  cent.  X  15 
respirations.  The  fact  that  the  diffusion  pressure  is  more  than 
sufficient  to  furnish  the  required  amount  of  oxygen,  may  be  gathered 

1  Hermann's  Handb.  der  Physiol.,  iv,  90. 

^  Aeby,  Bronchialbaum  der  Sauget.  und  des  Menschen,  Leipzig,  1880,  90. 


494  RESPIRATION 

from  the  following  calculation  of  Loewy.^  The  average  thickness  of 
the  membrane  separating  the  alveolar  air  from  the  blood,  amounts  to 
0.004  mm.  In  accordance  with  the  diffusion  rate  of  carbon  dioxid 
and  nitrous  oxid  through  the  lung  of  a  frog,  the  mammalian  lung  must 
yield  under  a  difference  of  pressure  of  35  mm.  Hg  about  67  c.c.  of  oxy- 
gen for  each  square  centimeter  of  alveolar  wall.  The  total  absorp- 
tion, therefore,  amounts  to  6083  c.c,  a  value  much  in  excess  of  the 
actual  oxj^gen  requirements  of  om'  body  in  quiet  breathing.  The  lat- 
ter is  only  about  250-300  c.c.  It  must  be  evident,  therefore,  that  the 
difference  in  the  partial  pressure  of  the  oxygen  could  safely  be  much 
reduced,  and  that  a  considerable  portion  of  the  total  respiratory  sm-- 
face  could  be  rendered  functionally  useless,  before  a  serious  disturbance 
in  the  normal  supply  of  this  gas  would  result.  In  the  same  way,  it  has 
been  established  that  the  tension  of  the  carbon  dioxid  in  the  blood 
could  be  materially  decreased  without  causing  a  fatal  reduction  in  its 
flow  into  the  alveoli;  in  fact,  as  the  speed  of  diffusion  of  this  gas  through 
a  moist  membrane  is  twenty-five  times  greater  than  that  of  oxygen, 
a  difference  in  pressure  of  only  0.3  mm.  Hg  would  suflEice  to  yield  the 
250  c.c.  of  CO2  normally  expired  per  minute. 

The  chemical  theory  necessitates  the  assumption  that  the  cells 
forming  the  alveolar  lining,  actively  participate  in  the  transfer  of 
the  gases.  This  end  is  accomplished  with  the  help  of  inherent  proc- 
esses which  are  very  similar  to  those  occurring  in  the  cells  of  the 
secretory  glands.  Hence,  we  find  here  a  condition  analogous  to  that 
existing  in  the  walls  of  the  air-bladder  of  the  fishes.  Inasmuch  as  the 
contents  of  this  organ  consist  at  times  of  as  much  as  85  per  cent,  of 
oxygen,  the  partial  pressure  of  this  gas  must  amount  to  90  atmospheres, 
while  that  of  the  oxygen  in  the  surrounding  water  scarcely  exceeds  J^ 
of  an  atmosphere  (Biot).  It  must  be  obvious,  therefore,  that  the  air- 
bladder  of  these  animals  is  filled  by  a  specific  secretory  activity  of  the 
lining  cells  which  is  controlled  by  a  special  nervous  mechanism.  ^ 

The  first  attempt  to  show  that  the  interchange  of  the  gases  in  the  lungs  is  not 
one  of  simple  diffusion  was  made  by  Bohr-^  in  1890,  but  these  results,  indicating 
that  the  oxygen  tension  of  the  blood  frequently  exceeds  that  of  the  alveolar  air, 
have  been  seriously  criticised  by  Krogh,  as  well  "as  by  Haldane  and  Douglass.  It 
seems  that  certain  errors  in  the  manipulation  of  the  aerotonometer  and  accidental 
variations  in  the  temperature  have  rendered  these  early  determinations  valueless. 
In  1907  Bohr  endeavored  to  substantiate  his  early  contentions  regarding  the 
secretory  activity  of  the  lung  by  the  following  experiment:  If  one  lung  is  permitted 
to  obtain  pure  air  and  the  other  air  containing  8.8  per  cent,  by  volume  of  CO2, 
the  latter  continues  to  give  off  CO2  in  spite  of  the  fact  that  the  tension  of  the  CO2 
in  the  venous  blood  of  the  right  side  of  the  heart  equals  that  of  an  atmosphere 
containing  only  5  per  cent,  of  this  gas  by  volume. 

This  entire  subject  has  recently  been  reinvestigated  by  Krogh, ^  whose  micro- 
aerotonometric  tests  have  shown  that  the  pressure  of  the  CO2  in  the  arterial 

1  Handb.  der  Biochemie,  iv,  1908. 

2  Bohr,  Jour,  of  PhvsioL,  xv,  1893,  494. 

3  Skand.  Archiv  fur  Physiol.,  ii,  1890,  231. 
« Ibid.,  xxii,  1910,  274. 


THE    CHEMISTRY    OF    RESPIRATION  495 

capillaries  and  in  the  alveolar  air  is  equal,  and  that  the  oxj^sen  tension  of  the 
lattiM-  is  always  slightly  above  that  of  the  l)lood.  In  addition,  attention  has  been 
called  to  the  fact  that  the  pidnionary  epithelium  lacks  all  the  essential  char- 
acteristics of  a  secreting  nienilirane.  In  the  mammals,  for  example,  this  lininj^ 
is  composed,  on  the  one  hand,  of  small  granular  cells  which  'are  located  in  the 
interstitial  spaces  between  the  capillaries  and,  on  the  other,  of  extremely  thin 
non-nucleated  cells  which  are  situated  directly  in  the  capillary  wall.  Besides, 
this  epithelial  covering  seems  to  be  entirely  lacking  in  birds,  so  that  the  surfaces 
of  the  capillaries  lie  in  direct  contact  with  the  air.  Pecidiarly  enough,  these 
animals  possess  a  very  intense  metabolism  and  must  therefore  be  in  a  position  to 
interchange  the  gases  with  the  greatest  possible  ease.  In  this  connection,  atten- 
tion should  also  be  called  to  the  fact  that  the  function  of  the  pulmonary  epithelium 
cannot  be  deduced  by  analogy  from  that  of  the  limiting  menil)rane  of  the  swim- 
bladder,  because  the  cells  composing  the  latter  are  augmented  by  other  cells  which 
form  the  so-called  "red  glands"  and  exhibit  true  secretory  properties.  This  same 
statement  could  not  justly  be  made  regarding  the  lining  cells  of  the  alveoli.  As 
another  point  against  the  secretory  theory  might  be  mentioned  the  fact  that  the 
respiratory  activity  may  be  altered  at  any  time  by  increasing  or  decreasing  the 
CO-,  content  of  the  inspired  air  or  of  that  of  the  blood  traversing  the  respiratory 
center.  Obviously,  the  assertion  might  be  made  that  if  the  lining  cells  of  the  alveoli 
were  actually  in  possession  of  a  secretory  power,  they  should  be  able  to  resist 
outside  influences  of  this  kind  and  should  be  under  the  direct  control  of  the  nervous 
system. 

Douglass  and  Haldane^  have  recently  attempted  to  solve  this  problem  in  an 
indirect  way  by  the  use  of  carbon  monoxid.  It  will  be  remembered  that  this  gas 
combines  with  the  hemoglobin  of  the  blood  to  form  the  more  stable  monoxid 
hemoglobin.  Thus,  if  blood  is  exposed  to  a  mixture  of  O2  and  CO,  a  certain 
portion  of  each  gas  eventually  unites  with  the  hemoglobin,  but  inasmuch  as  the 
latter  possesses  a  much  greater  avidity  for  CO  than  for  O2,  a  much  larger  amount 
of  CO  enters  into  this  combination.  Assuming  that  the  same  conditions  prevail 
in  the  body  during  the  inhalation  of  CO,  these  authors  permitted  an  individual 
to  breathe  a  certain  quantity  of  this  gas  until  the  blood  became  fully  charged 
with  it.  The  percentage  saturation  of  the  Hb  by  the  CO  was  then  determined. 
This  value  may  justly  be  regarded  as  indicating  the  O2  content  of  the  blood,  be- 
cause the  amount  of  this  gas  which  must  be  inhaled  simultaneously  with  the  CO 
in  order  to  produce  the  saturation  just  ascertained,  is  open  to  direct  calculation. 
These  tests  which  were  supplemented  by  inhalations  of  varying  quantities  of 
oxygen,  showed  that  the  pressure  of  the  oxygen  in  the  arterial  blood  remains 
below  that  of  the  air  in  the  alveoli  until  the  saturation  of  the  hemoglobin  with 
carbon  monoxid  surpasses  30  per  cent.  Beginning  at  this  point,  the  oxygen 
tension  decreases  and  is  finally  reversed.  This  observation  led  Haldane  to  con- 
clude that  the  epithelial  cells  of  the  alveoli  play  an  active  part  in  the  interchange 
of  the  gases.  Thus,  it  is  stated  that  these  lining  cells  gather  the  oxygen  under  a 
tension  of  15  per  cent,  and  force  it  to  the  other  side  of  the  membrane  until  its  ten- 
sion in  the  blood  greatly  exceeds  that  in  the  alveoli. 

Several  objections  may  be  raised  against  these  experiments  which  render  the 
conclusions  derived  from  them  practically  worthless.  In  the  first  place,  it  should 
be  noted  that  Haldane  has  employed  the  colorimetric  method  of  estimating  the 
degree  of  saturation  of  the  Hb  by  the  CO,  a  method  which  has  not  as  yet  been 
proved  to  be  absolutely  reliable.  Secondly,  it  cannot  rightly  be  assumed  that  the 
avidity  of  the  O2  and  Hb  remains  the  same  throughout  the  course  of  these  experi- 
ments, and  that  the  conditions  under  which  these  gases  unite  are  the  same  in  vivo 
as  in  vitro.  For  these  reasons,  as  well  as  others,  Haldane  has  modified  his  previous 
contention  somewhat,  and  now  seems  to  believe  that  the  interchange  of  the  gases 
is  accomplished  under  normal  conditions  by  ordinary  diffusion.     Under  abnormal 

I  Jour,  of  Physiol.,  xliv,  1912,  305. 


496  RESPIRATION 

conditions,  however,  when  the  oxygen  tension  in  the  alveolar  air  is  verj'  low,  the 
lining  cells  maj'  acquire  a  secretory  power. 

The  Interchange  of  the  Gases  Between  the  Blood  and  the  Tissues. 
The  Absorption  of  Gases  by  Liquids. — If  a  gas  is  brought  into  contact 
with  water,  a  certain  number  of  its  molecules  enter  the  latter  and  be- 
come dissolved,  the  amount  absorbed  being  dependent  upon  the  nature 
of  the  gas,  the  temperature  and  the  pressure  under  which  it  exists. 
Provided  that  these  factors  remain  unchanged,  an  equilibrium  is 
eventually  estabhshed,  during  which  the  water  retains  a  definite 
quantity  of  the  gas.  But  this  condition  of  saturation  does  not  signify 
that  the  gaseous  molecules  remain  absolutely  stationary,  because 
in  accordance  with  the  kinetic  theory  of  matter,  it  is  commonly  believed 
that  the  molecular  constituents  of  any  entity  are  in  constant  motion. 
In  many  cases,  they  pursue  a  definite  course  and  collide  with  one  another 
so  that  they  are  deflected  from  their  paths.  It  should  be  emphasized, 
however,  that  molecular  motion  does  not  consist  in  incessant  collisions, 
because  the  distances  which  molecules  actually  traverse  without 
striking  one  another  are  relatively  great.  Furthermore,  it  cannot 
be  denied  that  these  mechanical  interferences  seriously  impede  the 
general  progress  of  the  molecules.  But,  while  some  of  them  may  be 
momentarily  brought  to  a  standstill,  others  are  forced  onward  with 
a  certain  momentum  which  makes  them  exceed  their  average  velocity. 
In  the  outer  layers  of  the  water,  large  numbers  of  these  molecules 
strike  the  walls  of  the  receptacle  and  rebound,  while  elsewhere  many 
of  them  escape  into  the  overlying  mass  of  gas  only  to  reenter  the  water 
later  on.  In  the  state  of  saturation  just  as  many  molecules  leave  the 
water  as  enter  it. 

If  the  preceding  experiment  is  now  repeated  with  a  mixture  of 
gases,  it  will  be  found  that  practically  the  same  interchange  takes  place, 
the  absorption  of  each  constituent  being  proportional  to  the  pressure 
exerted  by  it,  i.e.,  to  its  partial  pressure.  Thus,  if  the  pressure  of  one 
of  the  gases  is  greater  in  the  atmosphere  than  in  the  water,  it  will 
pass  into  the  water,  and  vice  versa.  Moreover,  it  is  to  be  noted  that 
the  flow  of  this  particular  gas  is  independent  of  that  of  any  other  of 
the  constituents  of  this  mixture  and  may  be  increased  or  decreased  by 
simply  altering  its  partial  pressure  in  one  of  these  regions.^ 

The  absorption  behaves  toward  changes  in  temperature  in  an 
inverse  manner.  Furthermore,  inasmuch  as  these  changes  are  not 
proportional  to  one  another,  it  becomes  necessary  to  determine  the 
absorption  for  every  degree  of  change  in  temperature.  Thus,  it  has 
been  found  that  the  volume  of  oxygen  absorbed  by  one  volume  of 
water  at  0°  C.  amounts  to  0.0489  c.c,  that  of  carbon  dioxid  to  1.713 
c.c,  and  that  of  nitrogen  to  0.0234  c.c.  At  15°  C.  the  volume  of  these 
gases  absorbed  equals  0.0310  c.c,  1.0025  c.c.  and  0.0168  c.c, 
respectively.     As  a  means  for  comparison  we  have  the  so-called  coeffi- 

^Law  of  Henry,  Philos.  Transact.,  1803. 


THE    CHEMISTRY    OF    RESPIRATION  497 

cient  of  absorption,  by  which  is  meant  the  quantity  of  a  ^as  physicall}' 
absorbed  or  dissolved  in  1  c.c.  of  a  Uquid  at  0°  C.  and  under  a  pressure 
of  700  mm.  Hg. '  Essentiall}'-  the  same  changes  result  if  a  watery 
solution  is  brought  into  relation  with  a  mixture  of  gases,  provided,  of 
course,  that  no  chemical  attraction  arises  between  the  substances 
dissolved  therein  and  the  gases.  It  need  not  surprise  us,  however, 
to  find  that  the  absorption  is  less  now  and  gradually  decreases  as  the 
concentration  of  the  solution  is  increased. 

If  a  comparison  is  made  between  the  pressure  and  the  weight  of  the 
gas  absorbed,  i.e.,  its  density  or  the  number  of  molecules  in  a  certain 
volume,  it  will  be  found  that  at  a  constant  temperature  the  weight 
of  the  volume  al)sorbed  increases  and  decreases  in  direct  proportion 
to  the  increase  and  decrease  in  the  pressure.  To  illustrate,  the  volume 
of  oxygen  absorbed  by  one  volume  of  water  at  0°  C.  and  under  a  pres- 
sure of  700  mm.  Hg  amounts  to  0.0489  c.c.  If  the  pressure  is  now 
doubled,  the  volume  absorbed  remains  the  same,  but  its  weight  is 
doubled.  Quite  similarly,  a  lowering  of  the  pressure  below  700  mm. 
Hg  does  not  affect  the  volume  of  the  gas  absorbed,  but  solely  dimin- 
ishes its  weight  (Law  of  Dalton). 

The  absorption  of  the  gases  by  blood  or  by  blood-serum  cannot  be 
determined,  because  oxygen  and  carbon  dioxid  form  dissociable  chem- 
ical compounds.  In  fact,  even  nitrogen  has  been  said  by  Bohr  to 
possess  certain  chemical  avidities  which  do  not  permit  it  to  conform 
to  the  ordinary  laws  of  the  diffusion  of  the  gases.  This,  however, 
is  a  debatable  question.  At  all  events,  the  fact  that  the  blood  con- 
tains the  gases  just  mentioned  in  physical  solution,  as  well  as  in  a 
chemically  dissociable  state,  necessitates  a  brief  discussion  of  the 
combinations  which  they  may  enter. 

The  Extraction  of  the  Gases  from  the  Blood. — Supposing  for  the 
moment  that  we  are  dealing  with  a  gas  held  in  ordinary  physical  solu- 
tion, the  following  procedure  should  be  followed.  The  liquid  containing 
the  gas  is  placed  in  a  cylinder  and  its  upper  surface  is  brought  into 
firm  contact  with  a  piston,  the  weight  of  which  is  accurately  balanced 
by  a  counterweight.  If  this  entire  apparatus  is  now  placed  into  the 
receiver  of  an  air  pump,  from  which  the  air  may  be  gradually  exhausted, 
bubbles  of  gas  will  escape  from  the  hquid  and  collect  in  a  thin  layer 
between  its  surface  and  that  of  the  piston.  At  this  time,  therefore,  the 
piston  IS  being  balanced  by  the  pressure  of  the  escaping  gas  and  that 
existing  in  the  receiver  of  the  air-pump.  On  increasing  the  pressure 
in  this  compartment,  a  point  will  be  reached  at  which  the  gaseous 
molecules  again  begin  to  enter  the  liquid.  Consequently,  at  this  time 
the  impacts  of  those  molecules  which  are  just  leaving  the  liquid  are 
being  counter-balanced,  and  hence,  if  the  pressure  which  is  required 
to  accompUsh  this  end  is  noted,  we  are  in  possession  of  a  means  of 

^Bunsen,  Gasometr.  Methoden,  Braunschweig,  1877;  Hempel,  Gasanalyt. 
Methoden,  Braunschweig,  1900,  and  Berthelot,  Traite  pract.  de  I'analyse  des  gaz., 
Paris,  1906. 

32 


498 


RESPIRATION 


determining  the  pressure  or  tension  of  this  gas  in  the  liquid.  Thus, 
it  will  be  seen  that  a  gas  can  be  extracted  from  a  liquid  by  simply- 
bringing  it  into  relation  with  an  atmosphere  in  which  its  partial  pres- 
sure is  slight.     The  procedure  usually  followed  is  to  subject  the  liquid 


Fig.  255. — Gas  Pump  for  Extracting  the  Gases  of  Blood.  (Grehant.) 
M  and  F,  the  mercury  receivers;  P,  the  windlass  for  raising  and  lowering  M;  m,  a 
three-way  stopcock  protected  by  a  seal  of  mercury  or  water;  C,  a  cup  with  mercury  over 
which  the  receiving  eudiometer  is  placed  to  collect  the  gases;  B,  the  bulb  in  which,  after  a 
vacuum  is  made,  the  blood  is  introduced  by  the  graduated  syringe,  S.  By  means  of  the 
stopcock  m  the  vacuum  in  F,  caused  by  the  fall  of  the  mercury,  can  be  placed  in  commu- 
nication with  B.  After  the  gases  have  diffused  over  into  F,  M  is  raised,  and  when  the 
stopcock  m  is  properly  turned  these  gases  are  driven  out  through  C  into  the  receiWng 
tube.     The  operation  is  repeated  until  no  more  gas  is  given  off  from  B.     (Howell.) 

in  which  the  gas  is  dissolved,  to  the  vacuum  of  an  air-pump  or  to  bring 
it  into  relation  with  some  other  gas. 

The  gases  of  the  blood,  however,  present  certain  peculiarities  be- 
cause they  are  not  entirely  in  pure  physical  solution,  but  enter  loose 
chemical  combinations;  in  fact,  a  part  of  the  carbon  dioxid  forms  a 
stable  compound,  the  dissociation  of  which  necessitates  the  use  of 


THE    CHEMISTRY    OF   RESPIRATION 


499 


chemical  agents.  The  usual  procedure  then  is  to  expose  the  blood  at 
body-tenipcrature  to  as  pi^rfect  a  vacuum  as  can  be  obtained,  but  it 
must  have  be(>n  defibrinated  or  must  have  been  rendered  non-coagu- 
lablc  by  the  addition  of  an  oxalate  or  citrate  solution. 

The  Torricellian  vacuum  was  first  employed  for  the  extraction  of  the  gases  of 
the  blood  by  Ludwig  and  Setschenow.^  Air-pumps  of  simple  construction  have 
been  described  by  Pflii^er-and  (Irehant^  (Fig.  255)  and  one  of  greater  complexity 
by  Topler-Hagen.  The  latter  has  been  modified  by  Zuntz  and  Barcroft.''  It 
consists  of  a  Woulfe  bottle  (.4 )  filled  with  mercury  and  a  long  capillary  tube  which 
also  contains  mercury  (Fig.  256).     Bottle  A  is  connected  with  the  water  supply 


Fig.  256. — Barcroft's  Modification  op  the  Topler  Pump. 


tube  by  two  taps  W .  The  vacuum  (5)  is  shut  off  against  the  sulphuric  acid  cham- 
ber {E)  for  drying  the  gases  by  a  glassfioat  (F).  hX  F  a,  condenser  is  interposed 
through  which  a  stream  of  cold  water  is  kept  flowing.  The  blood  is  led  from  the 
cyUnder  A'  into  the  receptacle  G  as  soon  as  a  vacuum  has  been  established.  This 
end  is  accomplished  by  permitting  water  to  flow  through  the  tap  TF  into  the  Woulfe 
bottle  A.  The  mercury  is  then  forced  into  tube  5,  where  its  further  progress 
toward  E  is  finally  made  impossible  by  the  raising  of  the  glass  valve  Y .  Its 
only  exit  now  is  through  C  into  D.  If  the  influx  of  water  is  now  made  to  cease,  and 
the  second  tap  TF  is  opened,  the  mercury  assumes  its  original  position.  If  the  air 
is  at  this  time  prevented  from  entering  at  Z),  the  valve  Y  drops  downward  and  per- 

^  Ber.  der  Akad.  der  Wissensch.,  Wien,  1859. 

2  Unters.  aus  dem  physiol.  Institut  zu  Bonn,  1866. 

3  Compt.  rend.,  Ixxv,'  1872. 

<  Ergebn.  der  Physiol.,  vii,  1908,  699. 


500  EESPIRATION 

mits  the  air  from  the  receptacle  G  and  the  rest  of  this  connecting  tube  to  enter  the 
chamber  B.  This  process  is  repeated  until  a  high  vacuum  has  finally  been  attained. 
A  measured  quantity  of  l^lood  is  then  allowed  to  flow  from  the  graduated  cylinder 
K  into  the  receptacle  G  which  is  surrounded  by  warm  water  to  hasten  the  escape 
of  the  gases.  The  blood  boils  in  this  vacuum,  but  is  prevented  from  boiling  away 
by  the  condenser.     The  gases  given  off  by  it  are  then  collected  over  the  mercury. 

It  is  also  possible  to  determine  the  quantity  of  oxygen  or  carbon  dioxid  in  a 
chemical  way  without  the  use  of  the  pump.  Thus,  the  CO2  may  be  liberated  by 
adding  diluted  acids  to  the  blood  and  by  collecting  it  in  potassium  hydrate.  ^ 
Schultze^  has  descril>ed  a  simple  volumetric  method  for  the  estimation  of  CO2 
which  Rieliinder  has  applied  to  the  analysis  of  the  CO2  in  the  blood.  In  recent 
years  Haldane*  has  devised  an  apparatus  which  has  been  modified  by  Fr.  Miiller.'' 
It  is  based  upon  the  principle  that  the  oxygen  in  hemoglobin  may  be  ascertained  in 
a  quantitative  manner  by  adding  a  solution  of  potassium  ferricyanid  to  laked  blood. 
The  apparatus  consists  of  a  bottle  which  is  connected  with  a  receptacle  containing 
the  solution  just  mentioned.  It  also  communicates  with  two  burets  united  below 
by  a  connecting  piece.  The  second  buret  is  joined  to  a  l)ottle  which  is  used  as  a 
thermobarometer.  A  tube  leads  from  the  T-cannula  to  a  niveau  receptacle  filled 
with  slightly  acidified  water.  To  the  central  bottle  are  attached  two  glass  bulbs 
separated  from  one  another,  as  well  as  from  the  bottle,  by  stop-cocks.  The  upper 
bulb  contains  a  dilute  solution  of  ammonia  and  the  lower,  the  blood  to  be  ex- 
amined. 

A  perfect  constancy  of  the  temperature  having  been  attained,  note  is  made  of 
the  level  of  the  water  in  the  burets.  If  the  blood  and  the  solution  of  ammonia  are 
now  permitted  to  flow  into  the  central  bottle,  the  former  will  be  laked  immediately. 
Under  repeated  shaking  the  ferricyanid  is  then  added  to  the  blood  after  which  the 
level  of  the  water  in  the  burets  is  observed  at  intervals.  Its  maximal  fall  in  the 
buret  nearest  the  generator  indicates  the  volume  of  oxygen  evolved.  In  these 
determinations  close  attention  must  also  be  paid  to  the  temperature  as  well  as  to 
the  barometric  pressure. 

Haldane  and  Barcroft''  have  given  to  this  apparatus  a  more  convenient  form 
so  that  even  very  small  quantities  of  blood  may  be  examined  (Fig.  257).  Moreover, 
Mosso  and  Marro^  have  proved  that  this  procedure  may  be  made  to  include  a 
determination  of  the  carbon  dioxid  content  of  the  blood.  Tartaric  acid  is  em- 
ployed for  the  liberation  of  this  gas.  The  same  apparatus  may  also  be  employed 
as  a  differential  indicator  of  these  gases  in  two  different  samples  of  blood.  ^ 

In  the  latter  case  the  apparatus  consists  of  two  bottles  of  equal  size  (Fig.  257) 
which  are  connected  with  a  manometer  (1.0  mm.  bore)  filled  with  oil  of  cloves  of 
known  specific  gravity.  Into  one  of  these  receptacles  are  then  poured  1  c.c.  of  blood 
and  2  c.c.  of  ammonia,  made  by  adding  4  c.c.  of  strong  NH3  to  a  liter  of  water.  The 
blood  having  been  thoroughly  laked,  the  stoppers  are  anointed  with  vaselin  and 
their  inside  compartments  filled  with  0.2  c.c.  of  a  saturated  solution  of  potassium 
ferricyanid.  The  apparatus  is  then  placed  in  a  water  bath  for  about  five  minutes 
with  both  stop-cocks  open.  At  the  end  of  this  period  the  ferricyanid  solution  is 
allowed  to  trickle  into  the  laked  blood  under  repeated  shaking  of  the  entire  appara- 
tus. It  is  then  replaced  in  the  water  bath.  The  column  of  the  qil  of  cloves  at  the 
side  of  the  blood  is  now  brought  to  its  original  level  by  means  of  the  screw  clamp, 
after  which  the  difference  in  the  levels  on  the  two  sides  is  noted.     The  volume  of  the 

oxygen  evolved  equals   x    =   y  [  —)m  which  y  stands  for  the  difference  of  level 


1  F.  Kraus,  Archiv  fiir  exp.  Path.,  xxvi,  1890. 

^  Zeitschr.  fiir  die  landw.  Vers,  in  Oesterreich,  1905. 

3  Jour,  of  Physiol.,  xxii,  1898  and  xxv,  1900. 

^Pfliiger's  Archiv,  ciii,  1904,  541. 

6  Jour,  of  Physiol.,  XX viii,  1902,  232. 

®  Rend,  della  R.  Acad,  dei  Lincei,  xii,  1903. 

^  Barcroft,  Jour,  of  Physiol.,  xxxvii,  1908,  12. 


THE    niEMISTRY    OF    RESPIRATION 


501 


and  p  for  the  height  of  the  barometer.     P  may  be  taken  as  10,000  mm.,  so  that  the 

expression — may  be  made  to  serve  as  the  con.stant   (f)    of  the  apparatus.     Then 

X  =  y  X  c. 

Having  determined  the  oxygen  content  of  this-  sample  of  blood,  its  carbon 
dioxid  content  may  be  ascertained  by  the  same  procedure  with  the  aid  of  tartaric 
acid.  If  it  is  desired  to  compare  the  gas  content  of  two  different  samples  of  blood, 
they  are  placed  in  these  two  adjoining  receptacles,  1  c.c.  of  each  under  1.5.  c.c. 
of  weak  ammonia.  They  arc  then  immersed  in  the  water  bath  until  the  level  of 
the  oil  remains  constant.  The  blood  is  then  laked  in  the  usual  way.  If  the  same 
quantity  of  oxyhemoglobin  is  present  in  the.se  samples  of  blood,  the  level  of  the  oil 
in  the  two  tubes  remains  the  same;  while  if  imequal  amovmts  are  present,  the  more 
decidedly  venous  lilood  will  absorb  more  oxygen  from  its  bottle  than  the  other. 
Consequently,  the  level  of  the  oil  must  rise  on  this  side,  the  difference  in  the 


--::> 


tC-  - 


:U' 


Fig.  257. — Barcroft's  Blood-gas  Apparatus. 


levels  indicating  the  amount  of  oxygen  taken  up,  and  hence,  also    the  content  in 
hemoglobin. 


The  quantities  of  oxygen  and  carbon  dioxid  vary  greatly  in  different 
samples  of  arterial  and  venous  blood.  Much  depends  upon  the  char- 
acter of  the  blood-vessel,  or  rather,  upon  the  intensity  of  the  metabolism 
of  the  tissue  supplied  by  it.  Still  greater  differences  are  encountered 
if  the  blood  of  different  animals  is  examined.  Obviously,  these 
variations  pursue  a  course  parallel  to  the  hemoglobin  content,  as  well 
as  to  the  affinity  which  this  body  displays  toward  oxygen.  It  is  the 
general  opinion  that  the  percentage  of  oxygen  is  greater  in  carnivora 
than  in  herbivora  and  birds,  while  the  percentage  of  carbon  dioxid 
is  smaller.  The  experiments  of  Pfltiger  and  others  have  furnished 
such  values  as  are  included  in  the  following  table: 


502 


RESPIRATION 
100  C.C.  OF  ARTERIAL  BLOOD  CONTAIN: 


O 

CO2 

N 

r 

Average 

22.6 

34.3 

1.8 

Dog 

Maximal 

25.4 

42.6 

3  3 

Minimal 

18.7 

23.9 

1.2 

r 

Average 

14.0 

49.4 

Horse { 

Maximal 
Minimal 

16.6 
9.2 

55.5 
39.0 

f 

Average 

13.2 

34.0 

2.1 

Rabbit 

Maximal 

14.6 

36.5 

2.3 

^ 

Minimal 

10.7 

31.3 

1.7 

A  difference  of  9  per  cent,  was  frequently  encountered,  dependent 
entirely  upon  the  speed  of  the  extraction  of  the  gases;  in  fact,  inas- 
much as  the  oxidations  continue  for  some  time  after  the  blood  has 
been  removed,  a  greater  yield  of  carbon  dioxid  is  generally  obtained 
than  would  be,  if  these  processes  could  be  made  to  cease  immediately. 
But  naturally,  this  oxidation  is  restricted  to  the  formed  elements  of 
the  blood,  for  the  very  obvious  reason  that  their  metabolism  does  not 
cease  directly  after  their  escape  from  the  circulation. 

The  observations  of  Setschenow  upon  blood  withdrawn  directly 
from  the  arteries  of  man  have  given  21.6  c.c.  of  oxygen,  40.3  c.c.  of 
carbon  dioxid  and  1.6  c.c.  of  nitrogen  for  each  100  c.c.  of  blood.  Argon 
is  present  in  very  insignificant  amounts,  its  exact  value  being  about 
0.04  volume  per  cent.  Traces  of  hydrogen  and  carbon  monoxid  may 
also  be  present,  the  former  being  derived  from  the  intestinal  canal 
and  the  latter  from  the  air.  Thus,  it  may  be  said,  in  a  general  way, 
that  100  c.c.  of  arterial  blood  yield  about  60  c.c.  of  a  mixture  of  gases. 
In  the  venous  blood  of  the  dog  the  oxygen  varied  between  5.5  and 
16.6  c.c.  and  the  carbon  dioxid  between  38.8  and  47.5  c.c.  If  the  aver- 
age values  of  these  determinations,  namely  11.9  c.c.  and  44.3  c.c. 
respectively,  are  now  compared  with  the  figures  given  above,  the  fol- 
lowing averages  are  obtained  for  each  100  c.c.  of  blood  at  0°  C.  and 
under  a  pressure  of  760  mm.  Hg: 


Arterial  blood. 
Venous  blood . 


20  c.c.  O2 
5-12  c.c.  O2 


40  c.c.  CO2 
46^0  c.c.  CO2 


1-2  c.c.  N 
1-2  c.c.  N 


The  Condition  of  Oxygen  in  the  Blood. — The  plasma  of  the  blood 
is  a  watery  solution  containing  9  per  cent,  of  solids,  whereas  its  formed 
elements  embrace  40  per  cent,  of  solids.  At  this  time,  attention 
should  again  be  called  to  the  fact  that  the  absorption  of  oxygen  by  the 
blood  is  different  from  that  of  oxygen  by  water,  because  this  gas  enters 
into  a  chemical  combination  with  the  hemoglobin  of  the  red  cells. 
Normal  blood,  as  we  have  just  seen,  contains  about  20  volume  per  cent. 


THE    CHEMISTRY    OF    RESPIRATION  503 

of  this  gas,  while  100  c.c.  of  water  under  identical  conditions  are 
capable  of  absorbing!;  only  0.7  c.c.  (0.7  volume  per  cent.).  This  fact, 
that  the  oxygen  is  not  simply  absorbed  by  the  blood,  may  also  be 
deduced  from  the  observation  that  its  quantity  does  not  vary  directly 
with  its  partial  pressure  in  the  surrounding  medium.  It  is  a  well- 
known  fact  that  blood  ex])os(xl  to  the  vacuum  of  an  air-pump  does  not 
discharge  its  oxygcui  until  the  pressure  has  been  considerably  reduced. 
In  most  instances  a  diminution  to  about  half  an  atmosphere  is  re- 
quired before  this  gas  begins  to  escape.  This  corresponds  to  a  pressure 
of  oxygen  of  about  80  nun.  Hg.  At  about  70  mm.  Hg  the  dissociation 
is  intense,  and  becomes  more  and  more  rapid  as  the  pressure  declines 
toward  zero.  Meanwhile,  the  blood  changes  its  color  from  bright 
red  to  purple.  This  behavior  of  the  oxygen  clearly  proves  that  it  is 
not  hold  in  a  simple  physical  condition,  but  enters  into  a  dissociable 
union  with  some  constituent  of  the  blood. 

If  the  blood  is  now  centrifugalized,  it  will  be  found  that  the  plasma 
is  capable  of  absorbing  only  a  very  small  amount  of  oxygen,  while 
by  far  the  greatest  quantity  of  this  gas  is  held  in  the  corpuscular 
elements.  Only  0.65  volume  per  cent,  are  obtainable  from  the  plasma. 
Another  striking  difference  is  the  variability  of  the  oxygen  content 
of  the  plasma  in  consequence  of  changes  in  the  tension  of  this  gas  in 
the  surrounding  medium.  If  the  latter  is  increased,  a  greater  quan- 
tity of  oxygen  will  be  absorbed  by  it,  and  vice  versa.  Consequently, 
plasma  behaves  like  water;  i.e.,  it  follows  the  Henry-Dalton  law  of 
pressures  absolutely.  The  corpuscular  elements,  on  the  other  hand, 
do  not  show  a  direct  relationship  of  this  kind.  To  be  sure,  they  also 
take  up  a  greater  amount  of  oxygen  when  the  partial  pressure  of  this 
gas  is  high,  but  a  more  copious  absorption  takes  place  when  its  tension 
is  low.  As  higher  degrees  of  pressure  are  reached,  the  absorption 
becomes  less,  relatively  speaking. 

This  fact  may  be  illustrated  by  subjecting  defibrinated  blood  to  different 
tensions  of  oxygen.  At  the  temperature  of  the  body  a  pressure  of  10  mm.  led  to 
an  absorption  of  6  c.c.  of  oxygen,  while  30  mm.  of  pressure  sufficed  for  an  absorp- 
tion of  more  than  16  c.c.  Consequently,  these  low  tensions  were  sufficient  to 
produce  a  saturation  of  80  per  cent. ;  moreover,  while  higher  pressures  gave  rise  to 
a  still  greater  absorption,  the  increase  obtained  with  each  additional  rise  in  tem- 
perature, became  gradually  less.  Thus,  with  40  mm.  of  pressure  only  2  c.c.  were 
taken  up  in  addition  to  those  already  absorbed,  and  at  60  mm.  only  1  c.c.  It 
has  also  been  ascertained  that  the  degree  of  saturation  of  the  corpuscles  which  it  is 
possible  to  achieve  with  pure  oxygen,  namely,  with  a  partial  pressure  of  760  mm. 
Hg,  is  only  slightly  greater  than  that  obtainable  with  atmospheric  air  in  which  this 
gas  exerts  a  pressure  of  only  about  150  mm.  Whole  blood,  on  the  other  hand, 
takes  up  a  somewhat  greater  amount  of  oxygen  if  exposed  to  it  in  its  pure  form, 
but  this  oxygen  cannot  be  held  by  the  corpuscles,  because  they  are  quite  unaj)le  to 
acquire  much  more  than  may  be  chemically  united  with  them.  Consequently, 
this  extra  amount  must  be  held  by  them  in  a  physical  state  and  must  eventually 
overflow  into  the  plasma.  It  need  scarcely  be  mentioned  that  oxygen  thus  dis- 
solved in  the  plasma,  obeys  the  ordinary  laws  of  diffusion,  i.e.,  it  escapes  from  the 
blood  as  soon  as  its  partial  pressure  in  the  surrounding  medium  is  diminished  and 
long  before  its  chemically  combined  portion  is  liberated.     These  facts  indicate 


504  RESPIRATIOX 

that  practically  all  the  oxj'gen  is  held  by  the  corpuscles  in  the  form  of  an  unstable 
chemical  compound. 

It  has  been  shown  that  the  element  which  unites  with  the  ox\'gen, 
is  the  blood-pigment  or  hemoglobin  of  the  red  cells.  This  deduction 
finds  substantiation  in  the  fact  that  oxj-gen  is  bound  by  cn'stalline 
hemoglobin  in  quite  the  same  vray  as  by  whole  blood  and  in  perfect 
agreement  with  the  law  of  the  tension  of  the  gases.  Thus,  if  projected 
upon  an  abscissa,  the  cur\'e  of  aVjsorption  of  ox],'gen  by  hemoglobin 
forms  a  cun-ed  line,  the  convexity  of  which  Ls  turned  upward.  This 
result  proves  that  the  absorption  is  greatest  at  low  tensions  and  least 
at  high  tensions,  but  the  emplo\Tnent  of  hemoglobin,  instead  of  whole 
blood,  introduces  several  factors  which  may  render  a  direct  comparison 
of  the  results  practically  impossible.  In  the  first  place,  it  is  difficult 
to  procure  a  solution  of  this  pigment  which  can  justly  be  compared 
with  samples  of  whole  blood,  and  secondly,  it  is  not  always  a  simple 
matter  to  exclude  or  to  control  the  influence  of  the  carbon  dioxid  up>- 
on  the  binding  power  of  the  hemoglobin.  Thirdly,  although  oxj-gen 
and  hemoglobin  form  a  dissociable  compound,  their  dissociation  ten- 
sion may  be  varied  by  changes  in  temperature,  as  weU  as  by  the  char- 
acter of  the  salts  present.  Human  blood  corpuscles,  for  example,  are 
characterized  by  unusual  amounts  of  potassium,  whereas  dog's  cor- 
puscles contain  more  sodium.  The  former  salt  is  notably  more  effi- 
cient in  increasing  the  percentage  of  saturation  of  the  hemoglobin  than 
the  latter.  In  spite  of  these  difficulties,  however,  the  more  recent 
anah'ses  have  given  a  close  quantitative  agreement;  for  example,  inas- 
much as  1  g.  of  cr}'stallized  hemoglobin  takes  up  about  1.3  c.c.  of  ox\'- 
gen,  and  inasmuch  as  whole  blood  absorbs  about  20  volume  per  cent,  of 
this  gas,  the  blood  mu.st  contain  about  15  per  cent,  of  this  pigment. 
The  correctness  of  this  value  has  been  established  by  analytical  means; 
moreover,  the  absorption  of  the  oxj-gen  may  be  ascertained  directly 
by  determining  the  binding  power  of  the  iron  of  the  blood.  Inas- 
much as  this  substance  is  normally  held  in  measurable  quantities 
only  in  the  hemoglobin,  a  direct  comparison  may  be  made  between 
the  absorptive  power  of  this  pigment  and  its  content  in  iron.  It 
seems,  therefore,  that  the  hemoglobin  is  present  in  amounts  sufficient 
to  combine  with  practically  all  the  oxygen  ordinarily  contained  in  the 
blood. 

It  has  also  been  found  that  the  ox^-gen  maj-  be  displaced  from  the 
hemoglobin  by  equivalent  amounts  of  carbon  monoxid  and  nitrous 
oxid,  and  furthermore,  may  be  made  to  absorb  carbon  dioxid  in  greater 
quantities  than  can  be  accounted  for  by  the  laws  of  solution.  This 
fact  seems  to  suggest  that  the  hemoglobin  is  also  capable  of  entering 
into  a  loose  chemical  combination  with  this  gas,  although  it  does  not 
permit  its  oxj'gen  to  be  directly  displaced  by  it.  Conditions  may 
arise,  therefore,  which  lead  to  a  simultaneous  saturation  of  the  hemo- 
globin by  oxA'gen  and  carbon  dioxid,  thereby  altering  the  ox^-gen- 
carrj-ing  capacity  of  this  pigment.     As  has  been  stated  above,  it  is  the 


THE    CHEMISTRY    OF   RESPIRATION  505 

presence  of  this  carbon  dioxid  which  may  seriously  interfere  with  the 
determination  of  the  dissociation  curve  of  hemoglobin  and  oxygen  in 
whole  blood.  Its  action  is  similar  to  that  of  weak  acids,  such  as  lactic 
acid,  because  the  greater  its  tension,  or  the  greater  the  acidity  of  the 
blood,  the  greater  is  the  dissociation  of  the  oxygen.  It  possesses,  there- 
fore, a  solvent  action  which,  however,  it  does  not  unfold  unless  the 
oxygen  tension  is  markedly  diminished.  To  illustrate,  under  a  partial 
pressure  of  the  ox\'gen  of  150  mm.  Hg,  the  blood  remains  practically 
saturated  even  if  its  carbon  dioxid  tension  is  varied  within  phj^sio- 
logical  limits.  If  the  oxygen  pressure  is  now  reduced  to  20  mm.  Hg  and 
the  carbon  dioxid  pressure  to  5  mm.  Hg,  the  oxyhemoglobin  content 
of  the  blood  is  changed  to  67.5  per  cent.  This  value  may  be  further 
decreased  by  raising  the  carbon  dioxid  tension.  This  is  a  matter  of 
great  importance  to  the  body,  because  it  facilitates  the  liberation  of 
oxygen  in  those  parts  of  the  body  in  which  the  tension  of  this  gas  is 
low,  i.e.,  in  the  tissues.  By  means  of  this  peculiar  action  of  the  carbon 
dioxid,  the  hemoglobin  is  relieved  of  all  available  oxygen,  in  fact,  of 
more  than  it  would  allow  to  be  transferred  to  the  cells  under  ordinary 
conditions  of  ox^-gen  diffusion. 

The  Condition  of  Carbon  Dioxid  in  the  Blood. — While  the  amount 
of  carbon  dioxid  absorbed  by  blood,  is  dependent  upon  its  partial 
pressure  in  the  surrounding  medium,  a  direct  relationship  between 
these  factors  does  not  exist.  In  fact,  the  volume  of  this  gas  actually 
acquired  by  a  certain  quantity  of  blood,  is  much  greater  than  the 
volume  which  could  theoretically  be  allotted  to  it  upon  the  basis  of 
its  absorption  coefficient.  It  is  evident,  therefore,  that  only  a  part  of 
the  carbon  dioxid  is  retained  in  a  physical  state, while  another  part 
forms  a  dissociable  chemical  compound  with  some  constituent  of  the 
blood.  Conditions,  however,  are  not  so  simple  as  they  are  in  the  case  of 
oxygen,  which  gas  unites  with  only  one  element  of  the  blood,  whereas 
the  carbon  dioxid  is  bound  to  several,  i.e.,  to  the  plasma  as  well  as  to 
the  corpuscles. 

If  the  venous  blood  of  the  dog  is  exposed  to  the  vacuum  of  an  air  pump,  from 
45  to  50  c.c.  of  carbon  dioxid  may  be  extracted  from  each  100  cc.  of  blood.  It 
has  also  been  ascertained  with  the  help  of  the  aerotonometer  that  this  gas  is  held 
in  the  venous  current  under  a  pressure  of  about  40  mm.  Hg,  or  5-6  per  cent,  of  an 
atmosphere.  This  coexistence  of  a  relatively  high  carbon  dioxid  content  and 
low  degrees  of  pressure,  immediately  assumes  a  greater  significance  if  these  values 
are  compared  with  those  obtained  with  pure  solutions  of  this  gas.  Thus,  if  water 
and  carbon  dio.xid  are  shaken  under  a  pressure  of  760  mm.  Hg  and  at  the  tem- 
perature of  the  body,  about  50  per  cent,  of  the  gas  will  be  absorbed.  Quite 
similarly,  if  blood  plasma  is  treated  in  this  way,  it  will  take  up  an  almost  equally 
large  amount  of  this  gas,  while  whole  blood  assimilates  almost  150  c.c.  But 
naturally,  under  normal  conditions  the  blood  is  not  exposed  to  a  carbon  dioxid 
pressure  of  one  atmosphere  (760  mm.  Hg),  but  only  to  a  pressure  of  about  40 
mm.  Hg  =  J-iQ  of  an  atmosphere.  Hence,  all  the  carbon  dioxid,  excepting  2.01 
c.c.  for  every  100  c.c.  of  blood,  must  be  held  in  chemical  combination,  and  further- 
more, if  the  volume  of  the  corpuscles  is  reckoned  at  3^3  of  the  total  volume  of  the 
blood,  these  bodies  must  contain  0.59  c.c.  and  the  plasma  1.42  c.c.  of  this  gas  in  a 


506 


RESPIRATION 


physical  condition.  Thus,  it  will  be  seen  that  only  a  very  small  portion  of  the 
carbon  dioxid,  namely,  5  per  cent.,  behaves  in  accordance  with  the  Henry- Dalton 
law. 

In  endeavoring  to  locate  that  portion  of  the  carbon  dioxid  which  is  held  in  a 
condition  of  both  loose  and  stable  combination,  it  should  first  be  noted  that  the 
serum  and  plasma  contain  sodium  salts  with  which  this  gas  could  doubtlessly 
unite.  These  salts  are  sodium  carbonate  and  dibasic  soflium  phosphate.  It 
has  been  shown,  however,  that  the  quantity  of  available  alkali  which  Is  combined 
in  the  blood  in  the  form  of  carbonates  or  phosphates,  is  not  sufficiently  large  to 
bind  the  amount  of  carbon  dioxid  normally  present.  For  this  reason,  it  must  be 
concluded  that  at  least  a  part  of  this  gas  is  held  in  a  dissociable  condition  by 
certain  organic  substances. 

If  our  attention  is  now  directed  to  that  portion  of  the  carbon  dioxid  which  is 
united  with  the  alkali  of  the  blood,  we  are  immediately  confronted  by  the 
difficulty  that  its  quantity  cannot  be  determined  with  accuracy  and  that  even 
that  part  of  it  which  exists  as  bicarbonate,  shows  a  most  peculiar  chemical  be- 
havior. Thus,  defibrinated  blood  discharges  all  of  its  carbon  dioxid  with  greatest 
ease  as  soon  as  it  is  subjected  to  the  vacuum  pump,  and  even  without  the  addition 
of  an  acid  to  dissociate  it  from  its  bases.  A  bicarbonate  solution,  on  the  other 
hand,  po.ssessing  the  concentration  of  the  blood,  liberates  scarcely  more  than  half 
of  its  loosely  bound  carbon  dioxid.  If  sodium  bicarbonate  Ls  then  added  to  whole 
blood,  all  of  its  carbon  dioxid  can  be  obtained  with  the  aid  of  the  pump.  To 
these  data  should  also  be  added  the  fact  that  the  expo.sure  of  plasma  or  serum 
to  the  vacuum  does  not  result  in  a  complete  liberation  of  the  carbon  dioxid.  In 
order  to  obtain  it  in  its  entirety,  it  is  necessary  to  add  an  acid  so  that  this  so-called 
"fixed  carbon  dioxid"  may  first  be  dissociated  from  its  binder.  While  this  point 
has  not  been  entirely  cleared  up  as  yet,  it  is  doubtlessly  true  that  the  carbon 
dioxid  is  contained  chiefly  in  the  plasma  where  it  exists  as  sodium  carbonate  or 
bicarbonate.  A  certain  amount  of  it  is  also  held  in  the  corpuscles,  in  all  probability 
in  combination  with  the  sodium. 

With  reference  to  the  organic  combinations  of  carbon  dioxid,  it  should  first 
be  stated  that  the  most  conspicuous  of  these  is  the  loose  union  which  this  gas  is 
capable  of  forming  with  the  hemoglobin.  At  this  time,  however,  reference  is  had 
solely  to  the  alkali  free  portion  of  this  pigment,  namely,  to  its  globin  molecule. 
If  the  hemoglobin  content  amounts  to  15  per  cent.,  and  the  carbon  dioxid  tension 
to  30  mm.  Hg,  each  100  c.c.  of  blood  contain  8.1  c.c.  of  thLs  gas  in  combination 
with  the  hemoglobin.  In  addition,  it  has  previously  been  shown  that  0.59  c.c. 
are  present  in  the  physical  state,  which  makes  in  all  8.7  c.c.  We  know,  however, 
that  the  total  absorption  of  carbon  dioxid  by  the  red  corpuscles  at  a  tension  of  30 
mm.  Hg  amounts  to  about  14  c.c,  and  hence,  it  must  be  concluded  that  the  re- 
maining 5  c.c.  are  united  with  other  constituents  of  these  bodies,  in  all  probability 
with  the  alkali  as  bicarbonate  and  in  a  small  measure  also  with  the  lecithin.  It 
has  also  been  shown  that  the  carbon  dioxid  is  capable  of  forming  certain  unstable 
compounds  with  the  proteins  of  the  plasma.  As  a  general  summary  it  might  be 
well  to  give  the  table  compiled  by  Loewy'  which  is  based  upon  the  fact  that  under  a 
pressure  of  30  mm.  Hg  each  100  c.c.  of  arterial  blood  yield  40  c.c.  of  carbon  dioxid. 
This  total  quantity  is  distributed  as  follows: 


In  blood, 
c.c. 


Physically  absorbed 

Held  as  sodium  bicarbonate. . 
Held  in  organic  combinations 


1.9 
18.8 
19.3 


1  Handbuch  der  Biochemie,  iv,  1908. 


THE    CHEMISTRY    OF   RESPIRATION  507 

The  Condition  of  Nitrogen  in  the  Blood. — By  far  the  pcroatcst 
amount  of  the  nitrogen  present  in  circulating  blood,  is  held  in  solu- 
tion and  is  therefore  subject  to  the  law  of  Henry.  The  same  state- 
ment may  be  made  regarding  blood  kept  outside  the  ])ody,  if  it  is 
saturated  with  atnios})heric  air.  It  is  true,  however,  that  l)lood  al- 
ways absorbs  a  larger  amount  of  nitrogen  than  is  taken  up  by  an  equal 
volume  of  air  when  subjected  to  the  same  conditions.  This  fact 
tends  to  prove  that  a  small  portion  of  this  gas  is  held  in  combination. 
Moreover,  the  presence  of  this  extra  amount  cannot  be  dependent 
upon  a  special  activity  of  certain  tissues  for  the  obvious  reason  that 
blood  experimented  with  outside  the  body,  behaves  in  precisely  the 
same  manner.  The  separate  determinations  of  the  nitrogen  absorp- 
tion of  the  plasma  and  corpuscles  have  shown  that  the  nitrogen  con- 
tent of  the  former  is  proportional  to  the  tension  of  this  gas,  whereas  that 
of  the  latter  is  not.  Hence,  it  may  be  concluded  that  the  corpuscles 
are  the  element  most  directly  concerned  in  this  absorption.  Besides, 
it  has  been  proved  by  Bohr^  that  this  union  takes  place  solely  in  the 
presence  of  oxygen  and  that  tlu^  factor  primarily  responsible  for  it  is 
the  hemoglobin.  This  investigator  surmises  that  the  nitrogen  is  held 
here  in  the  form  of  an  unstable  oxid,  the  functional  significance  of 
which  has  not  been  established. 

Internal  or  Tissue  Respiration. — The  freshly  aerated  blood  tra- 
versing the  pulmonary  veins,  left  side  of  the  heart  and  systemic 
arteries  is  in  a  state  of  almost  complete  saturation  with  oxygen  which 
is  held  here  under  a  pressure  of  at  least  100  mm.  Hg.  It  has  been 
shown  above  that  its  saturation  amounts  to  about  90  per  cent.,  and 
that  this  degree  of  saturation  can  be  obtained  with  an  oxygen  tension 
of  little  more  than  30  mm.  Hg.  Thus,  it  will  be  noted  that  the  oxygen- 
carrying  capacity  of  the  blood  is  amply  safeguarded,  at  least  as  far 
as  pressure  is  concerned.  This  is  also  shown  by  the  fact  that  this 
type  of  blood  may  be  shaken  with  atmospheric  air  at  the  tempera- 
ture of  the  body  without  absorbing  more  than  about  2  volume  per 
cent,  of  oxygen  in  addition  to  that  just  stated.  Venous  blood,  on 
the  other  hand,  requires  8  to  10  volume  per  cent,  of  oxygen  for  its 
saturation. 

The  blood  traversing  the  capillaries  of  the  different  tissues  is 
brought  into  diffusion  relation  with  the  cells  through  the  intervention 
of  the  lymph.  It  is  a  well-known  fact  that  the  cells  acquire  oxj^gen 
constantly  and  give  off  carbon  dioxid.  It  is  evident,  therefore,  that 
the  oxygen  tension  is  higher  in  the  blood  than  in  the  tissues,  whereas 
that  of  the  carbon  dioxid  is  higher  in  the  tissues  than  in  the  blood. 
Thus,  the  physical  conditions  are  such  that  the  oxygen  must  flow  from 
the  blood  into  the  cells,  while  the  carbon  dioxid  must  pass  from  the 
cells  into  the  blood,  as  follows: 

^  Compt.  rend.,  cxxiv,  1897,  414. 


508  RESPIEATION 


rv.„ TT„               Carbon  dioxid, 

Oxygen,  mm.  Ilg                     ^^^_  jjg 

Arterial  blood 

100 

i 

35 

Capillary  wall 

t 

Tissue 

0 

50-70 

As  far  as  the  exchange  of  the  oxygen  is  concerned,  the  conditions  exist- 
ing here  are  the  same  as  those  prevaiUng  when  the  blood  is  subjected 
to  the  vacuum  of  an  air-pump.  The  neighboring  tissues  are  always 
greedy  for  oxygen,  and  abstract  even  the  last  traces  of  this  gas  from 
the  adjoining  lymph.  The  latter  in  turn  must  replenish  its  oxygen 
content  by  withdrawing  a  corresponding  amount  from  the  blood. 
In  this  way,  a  descending  scale  of  oxygen  tensions  is  produced,  begin- 
ning with  the  red  corpuscles  and  the  plasma  and  lymph  and  terminating 
in  the  interior  of  the  cell.  But  while  the  speed  of  the  capillary  flow 
is  sufficiently  slow  to  allow  these  interchanges  between  the  blood  and 
the  tissues  to  be  completed  with  plenty  of  time  to  spare,  the  individual 
red  cells  never  tarry  long  enough  at  these  c(41s  to  lose  their  entire 
store  of  oxygen.  Only  if  these  corpuscles  arc  prevented  from  recu- 
perating their  losses  in  the  lungs  can  their  oxygen  store  be  depleted 
further  until,  as  occurs  in  asphyxia,  the  last  traces  of  this  gas  have 
been  removed  from  them.  It  has  been  pointed  out  above  ^  that  the 
evolution  of  the  oxygen  by  the  hemoglobin  is  greatly  facilitated  by  carbon 
dioxid,  this  effect  being  especially  marked  in  conditions  of  low  oxygen 
tension. 


CHAPTER  XL 
THE  SEAT  AND  NATURE  OF  THE  OXIDATIONS 

The  Oxidative  Power  of  the  Tissues. — It  is  commonly  accepted 
to-day  that  the  seat  of  the  oxidations  is  in  the  tissues  and  not  in  the 
blood,  as  has  been  suggested  by  A.  Schmidt^  and  Pfliiger.^  Thus,  we 
are  accustomed  to  compare  the  body  to  a  steam  engine  and  to  speak  of 
the  "burning  up"  of  foodstuffs  in  a  manner  indicative  of  the  processes 
taking  place  during  an  ordinary  combustion.  But  while  it  seems  to  be 
true  that  the  reductions  are  confined  in  their  entirety  to  the  cells,  the 
fact  must  not  be  lost  sight  of  that  they  are  not  always  completed  by 
the  same  group  of  cells,  i.e.,  while  a  certain  colony  of  cells  may  incite 

1  Barcroft,  Respiratory  Function  of  the  Blood,  1914. 

2  Arbeiten  aus  dem  physiol.  Inst,  zu  Leipzig,  li,  1867,  99. 

3  Pfltiger's  Archiv,  i,  1816,  98. 


THE    SEAT    AND    NATURE    OF    THE    OXIDATIONS  509 

tho  oxidation,  some  othcn-  tissuo  may  bo  calkxl  iii)()n  to  form  the  final 
product. 

Tho  tissuos  possess  a  vory  ])ronoiinco.d  avidity  for  oxygen.  This 
has  been  shown  in  a  very  convincing;  manner  by  Elirhch.  A  saturated 
solution  of  methylene-blue  was  injected  into  the  venous  bloodstream 
of  an  animal.  After  an  interval  of  ten  minutes  it  was  kilkul  and  its 
organs  fully  exposed  to  tho  air.  The  tissues  which  exliibitiMl  at  first 
their  natural  color,  soon  assumed  a  decidinlly  l)luc  color.  It  is  evident, 
therefore,  that  they  are  able  to  decompose  the  comparatively  stable 
methylene-blue  into  a  colorless  product,  which  on  exposure  to  the  air 
is  again  oxidized  into  methylene-blue.  It  has  also  been  noted  that 
hemoglobin-like  bodies  are  present  in  the  cytoplasm  of  the  colls  of  the 
worms,  presumably  for  the  purpose  of  effecting  respiratory  interchanges. 
In  addition,  Lillie^  has  found  that  the  colored  products  of  the  oxida- 
tions, such  as  may  be  obtained  in  the  course  of  indophcnol  and  similar 
reactions,  accumulate  chiefly  in  the  vicinity  of  the  nuclei.  Some 
light  is  also  thrown  upon  this  question  by  the  fact  that  the  tissues 
contain  large  quantities  of  carbon  dioxid  and  that  this  gas  is  present 
in  considerable  amounts  in  the  lymph  occupying  the  peripheral 
radicles  of  the  lymphatic  system.  It  might  also  be  mentioned  that 
a  frog  may  be  kept  alive  even  after  its  blood  has  been  replaced  by 
physiological  salt  solution,  by  simply  placing  the  animal  in  an  atmos- 
phere of  pure  oxygen.  Inasmuch  as  the  consumption  of  oxygen  and 
the  production  of  carbon  dioxid  are  had  in  this  instance  even  in  the 
absence  of  the  blood,  these  processes  must  actually  be  completed  in 
the  tissues.  The  same  result  may  be  obtained  with  excised  muscles, 
in  which  case  the  production  of  carbon  dioxid  follows  a  course  parallel 
to  the  activity  and  general  condition  of  this  tissue. 

In  whatever  form  the  energy  of  the  body  may  be  liberated,  its 
source  lies  in  cellular  combustions  which  in  turn  necessitate  respiratory 
interchanges.  The  nature  of  these  microchemical  and  microphysical 
processes  is  not  clearly  understood,  nor  has  the  chemist  been  able  to 
form  a  concise  picture  regarding  the  changes  that  occur  during  one  of 
the  simplest  possible  combustions.  On  this  account,  it  is  quite 
impossible  to  describe  these  processes  in  anything  more  than  a  very 
general  way.  When  the  blood  enters  the  tissues,  it  delivers  not  only  a 
definite  amount  of  oxygen,  but  also  certain  amounts  of  nutritive  mate- 
rial in  the  form  of  proteins  or  amino  acids,  fats  and  sugars.  These 
substances  are  acted  upon  within  the  boundaries  of  the  cells.  Con- 
sequently, the  processes  of  life  consist  in  an  uninterrupted  change  in 
energy  which  presents  itself  as  a  conversion  of  latent  energy  into  work, 
heat  and  electricity.  It  is  to  be  noted,  however,  that  animals  are  not 
capable  of  sustaining  themselves  unless  fully  formed  organic  sub- 
stances are  placed  at  their  disposal,  and  hence,  the  amount  of  energy 
which  they  produce,  is  absolutely  dependent  upon  their  power  of  reduc- 
ing these  organic  molecules.     Plants,  on  the  other  hand,  are  able  to 

1  Am.  Jour,  of  Physiol.,  vi,  1902,  15. 


510  RESPIKATION 

form  these  complex  substances  from  inorganic  material  by  permitting 
carbon  dioxid  and  water  to  act  in  the  presence  of  sunlight.  Obviously, 
therefore,  animal  life  depends  upon  the  products  of  the  higher  plants, 
for  the  reason  that  the  latter  contain  energy-rich  organic  material. 

While  these  general  facts  are  incontestable,  much  uncertainty 
still  prevails  regarding  the  nature  of  these  reducing  processes.  In  its 
widest  sense,  the  term  oxidation  is  applied  to  any  chemical  reaction 
which  results  in  an  increase  of  the  positive  or  a  decrease  of  the  nega- 
tive valencies  of  a  compound.  Whether  or  no  oxygen  or  some  other 
agent  is  the  cause  of  the  reduction  is  not  of  deciding  value.  Thus,  the 
evolution  of  iodin  during  the  action  of  ferric  chlorid  upon  potassium 
iodid  is  essentially  an  oxidation,  as  may  be  gathered  from  the  fol- 
lowing formula: 

+  +  +---    +      -     ++  ---     + 

Fe  +  3C1  +  K  +  J  =  Fe  +  3C1  +  K  +  J 

This  process  has  resulted  in  the  passage  of  a  positive  charge  of  elec- 
tricity from  the  ferric  atom  to  the  iodin  atom,  or  the  transfer  of  a  negative 
charge  of  electricity  from  the  iodin  ion  to  the  ferric  ion.  It  will  be  seen 
that  a  substance  which  freely  yields  a  negative  charge  is  a  very  active 
reducing  agent,  while  a  substance  which  readily  liberates  a  positive 
charge  is  a  powerful  oxidizing  agent.  Upon  this  basis,  oxygen  may  be 
said  to  act  as  an  oxidizing  body,  because  it  possesses  the  power  of 
removing  a  negative  charge  from  other  substances  and  of  attaching 
itself  to  them  as  an  oxygen  ion,  or  as  electronegative  oxygen.  ^ 

At  this  time,  however,  we  are  chiefly  concerned  w4th  those  proc- 
esses which  are  consummated  in  the  living  tissues  with  the  aid  of  oxygen. 
These  reductions  belong  to  the  class  of  the  slow  reactions,  and  are  not 
simple  combustions,  because  the  oxidations  are  generally  initiated 
by  reductions  participated  in  by  various  ferments,  i.e.,  the  complex 
molecules  are  first  simplified  by  catalytic  agents  before  they  are  actu- 
ally oxidized.  It  should  also  be  remembered  that  these  oxidations  may 
result  in  many  cases  without  any  apparent  stimulus,  while  in  others  the 
substances  must  first  be  activated  by  some  outside  agent.  Thus, 
metallic  sodium,  phosphorus  and  certain  organic  bodies  bind  free  oxy- 
gen even  at  ordinary  temperatures,  while  the  rare  metals,  wood  and  coal 
must  first  be  exposed  to  a  high  temperature.  The  former  process 
takes  place  slowly  and  the  latter  with  considerable  speed.  Quite  simi- 
larly, foodstuffs  possess  no  tendency  to  take  up  atmospheric  oxygen 
under  ordinary  conditions  but  may  be  made  to  unite  with  this  gas 
by  heating  them.  Their  combustion  may  be  incited  immediately  by 
exposing  them  to  the  temperature  of  a  flame,  while  at  the  temperature 
of  the  body,  the  upper  limit  of  which  is  near  40°  C,  their  oxidation 
is  slow  and  gives  rise  to  intermediary  substances.  For  this  reason, 
they  are  classified  as  dysoxidizable  substances. 

^  Barcroft,  Ergebn.  der  Physiol.,  viii,  1908,  and  Winterstein,  Dissertation, 
Jena,  1906. 


THE  SEAT  AND  NATURE  OF  THE  OXIDATIONS       511 

In  the  second  place,  it  should  be  remembered  that  a  substance 
may  be  very  closely  allied  to  one  of  the  known  oxidizable  bodies,  and 
still  fail  completely  in  being  oxidized  by  the  tissues.  Thus,  it  has  been 
found  that  only  four  of  the  sixteen  sugars,  possessing  the  formula 
CeHioOe,  namely,  glucose,  fructose,  galactose  and  mannose,  are 
acted  upon  by  the  cells,  while  the  others  cannot  be  utilized.  In  the 
third  place,  a  tissue  may  lose  its  power  of  reducing  certain  foodstuffs 
completely,  a  condition  met  with  in  diabetes  mellitus.  Consequently, 
the  cell  must  possess  a  certain  chemicophysical  constitution  which 
becomes  completely  disarranged  in  the  course  of  certain  diseases 
with  the  result  that  formerly  assimilable  substances  are  rendered  non- 
assimilable. It  is  evident,  therefore,  that  the  general  arrangement  of 
the  intracellular  material  constitutes  the  principal  factor  in  the  de- 
termination of  the  manner  in  which  the  dysoxidizable  foodstuffs 
combine  with  the  oxygen.  On  this  account,  there  is  imparted  to  the 
oxidations  a  definite  specificity  and  a  limit  is  set  to  them  in  conformity 
with  the  requirements  of  the  dilTcrent  tissues.  Consequently,  the 
magnitude  of  the  oxidation  is  regulated  by  the  tissue  itself  and  not  by 
the  amount  of  oxygen  actually  available.  Thus,  inhalations  of  pure 
oxygen  cannot  augment  the  oxidations,  because  the  tissues  are  already 
acting  at  their  fullest  capacity.  The  oxygen  which  is  required  for 
these  processes  may  be  furnished  either  in  a  free  or  bound  state. 
In  the  latter  case,  it  is  in  combination  with  some  of  the  nutritive  sub- 
stances. As  bound  oxygen  must  also  be  regarded  the  oxygen  of  water 
which,  on  account  of  its  wide  distribution,  must  play  a  most  important 
part  in  biological  oxidations.  The  latter  are  commonly  designated 
as  hydrolj^ic  oxidations. 

As  slow  combustions  are  the  rule  in  living  matter,  the  energy  which 
is  required  to  instigate  these  processes  must  be  furnished  by  the  sub- 
stances to  be  oxidized.  The  latter,  therefore,  must  possess  the  power 
of  activating  the  molecular  oxygen,  and  hence,  the  real  purpose  of 
respiration  is  to  allow  the  mechanism  of  the  activation  of  oxygen  to 
be  set  in  motion.  Unfortunately,  however,  the  nature  of  this  process 
is  not  clearly  understood,  although  several  theories  have  been  formu- 
lated to  serve  as  possible  explanations.^ 

The  theories  regarding  the  activation  of  oxygen  may  be  divided 
into  two  groups,  namely:  those  which  assume  that  the  oxygen  is  first 
of  all  split  into  an  active  modification  and  those  which  hold  that  the 
molecules  of  oxygen  are  used  in  their  complete  form.  Among  the 
former  may  be  mentioned: 

1.  The  ozone-autozone  theory  of  Schonbern  and  Clausius  which  assumes  that 
the  inert  oxygen  appears  in  the  form  of  two  different  and  active  modifications. 

2.  The  ionization  theory  of  van't  Hoff  which  holds  that  the  modifications  of 
the  oxygen  are  not  chemically  different  but  only  carrj'  different  electrical  charges. 

^  A  more  detailed  account  will  be  found  in  Oppenheimer's  Handbuch  der 
Biochemie,  Jena,  1913,  or  in  Mathews.  Physiol.  Chemistry,  New  York,  1915.  Also 
see  Engler  and  Weissberg,  Ivrit.  Studien  liber  die  Vorg.  der  Autoxydation,  Braun- 
schweig, 1904. 


512  KESPIRATION 

t 

3.  The  theory  of  Hoppe-Seyler  denies  these  peculiarities  of  the  oxygen-fraction 
and  explains  this  reaction  upon  the  basis  of  reductions  in  which  nascent  hydrogen 
plays  a  part.  It  is  said  that  reducing  substances  are  formed  by  the  hydrolytic 
splitting  of  the  foodstuffs  in  consequence  of  ferment  activity.  The  atomic  hydro- 
gen acting  upon  the  oxygen,  forms  water  during  w  hich  process  some  atomic  oxygen 
is  left  over  which  is  used  to  oxidize  the  split  products  of  the  fermentation. 

Traube,^  on  the  other  hand,  advocates  the  view  that  the  molecule  of  oxygen  acts 
in  its  entirety.  He  assumes,  however,  that  the  oxidizable  substances  are  not 
acted  upon  by  free  oxygen  but  only  by  the  boimd  oxygen  of  the  water.  Thus,  it 
is  stated  that  the  molecule  of  water  is  first  split  into  its  components,  oxygen  and 
hydrogen,  and  that  the  former  is  comljined  with  the  oxidizable  body  and  the  latter 
with  one  whole  molecule  of  oxj'gen  to  form  hydroperoxid.  This  theory,  however, 
does  not  give  satisfactory  answer  to  the  question  of  why  the  oxidizable  substance 
prefers  bound  oxygen  to  free  oxygen  and  why  the  latter  selects  the  hydrogen  of  the 
molecule  of  water  and  not  the  oxidizable  body.  But,  this  theory  possesses  the 
advantage  of  being  more  truly  chemical,  because  it  minimizes  the  atomic  action  of 
oxygen  and  calls  attention  to  the  primary  formation  of  hydroperoxid.  Much 
greater  emphasis  has  been  placed  upon  this  process  by  Engler^  and  Bach^  who  be- 
lieve that  the  oxygen-molecule  0  =  0  is  incompletely  split  by  the  free  energy 
of  the  oxidizable  one,  so  that  —  0  —  0  —  groups  arise  which  combine  with  the 
former  under  the  formation  of  primarj'  peroxid.  Inasmuch  as  one-half  of  the 
oxygen  is  contained  in  these  peroxids  in  a  loose  and  active  state,  it  can  be  trans- 
ferred without  difficulty  to  other  oxidizable  substances. 

Hydrolytic  oxidations  include  first  of  all  those  processes  which  are 
accomplished  with  the  help  of  the  peroxid-oxygen  and  secondly,  those 
which  are  carried  on  at  the  expense  of  the  hydroxyls  of  water.  But, 
the  separation  of  the  latter  necessitates  the  presence  in  the  substance 
of  a  relatively  large  amount  of  energy  consisting  in  an  affinity  for  the 
hydroxyls.  Substances  of  this  kind  are  few  in  number  and  hence,  it 
generally  happens  that  two  substances  take  part  in  the  hydrolysis,  one 
of  which  attracts  the  hydroxyl  and  the  other  the  hydrogen.  As  an 
example  of  this  type  of  oxidation,  Bach^  cites  the  splitting  of  water 
by  hypophoric  acid  or  its  salts  in  the  presence  of  metallic  palladium. 

While  the  peroxid  theory  of  combustion  as  such  enables  us  to 
explain  many  phenomena  of  life  which  would  otherwise  remain  hidden 
to  us,  several  facts  have  been  added  to  it  in  more  recent  years  which 
render  it  even  more  serviceable.  Thus,  it  has  been  established  that 
the  oxidations  do  not  actually  affect  the  substance  of  the  cells  and 
cause  its  destruction,  but  merely  take  place  in  its  presence  under  the 
influence  of  specialized  ferments.  The  latter,  of  course,  are  a  product 
of  the  cells  and  hence,  we  are  dealing  in  this  case  with  a  chemical 
process  during  which  the  organized  cytoplasm  does  not  suffer.  As 
an  analogous  reaction  might  be  mentioned  the  conversion  of  sugar 
into  alcohol  and  carbon  dioxid  by  the  living  yeast  cell. 

The  biological  oxidations  are  slow  combustions,  and  as  such  must 
be  subject  to  the  influence  of  catalytic  agents.  In  the  sense  of  Ostwald, 
therefore,  these  processes  are  catalyses,  i.e.,  true  reactions,  instigated 

iChem.  Berichte,  xv,  1882,  659;  xviu,  1885,  1877,  and  xviii,  1885,  1890. 

2  Ibid.,  XXX,  1897,  1669. 

3  Compt.  rend.,  cxxiv,  1897,  951. 

^  Chem.  Berichte,  xlii,  1909,  4463. 


THE    SEAT   AND    NATURE    OF   THE    OXIDATIONS  513 

by  an  outside  factor  which  docs  not  enter  into  the  formation  of  the 
end-iiroduct.  This  view  is  strengthened  consich'rably  by  the  fact 
that  Hving  substance  contains  tlirce  ty])es  of  catalyzing  agents  in  the 
form  of  ferments,  namely,  oxidases,  peroxidases  and  perhydridases. 
Since  these  ferments  possess  a  special  function  in  so  far  as  they  com- 
plete the  process  of  respiration,  ttiey  may  be  classified  as  refijnratory 
ferments.  As  such  they  are  comparable  to  the  class  of  the  "digestive" 
ferments.  Thus,  a  fat-splitting  enzyme  (lipase)  and  protein-spUtting 
enzymes  (proteases)  have  been  isolated  from  many  tissues,  and  fer- 
ments have  also  been  found  which  act  upon  starch  (amylase)  sugar 
(diastase)  and  glycogen  (glycogenase).  -The  fact  that  such  catalyzing 
agents  exist  in  tissues  is  well  illustrated  by  the  phenomenon  of  auto- 
lysis or  self-digestion.  If  a  tissue  is  removed  from  the  body  under 
aseptic  conditions  and  is  kept  warm  and  moist,  it  will  finally  be 
digested.  The  same  end-products  are  then  formed  as  may  be  obtained 
by  boiling  this  tissue  with  acids. 

In  general,  therefore,  it  may  be  said  that  the  reductions  in  living 
matter  occur  either  in  the  presence  or  in  the  absence  of  free  or  bound 
oxygen.  At  this  time,  however,  we  are  chieflj^  concerned  with  those 
of  the  first  type,  namely,  with  the  respiratory  reductions.  In  accord- 
ance with  the  foregoing  discussion  it  must  now  be  evident  that  the 
purpose  of  respiration  is  the  burning  up  of  the  simplest  constituents 
of  the  body.  This  combustion  is  made  possible  by  the  respiratory 
ferments  which  are  produced  by  the  cell  and  exert  their  action  as 
soon  as  the  foodstuffs  have  been  sufficiently  simplified  by  the  ferments 
of  the  digestive  type.  The  former,  therefore,  are  organic  catalyzing 
agents  which  may  be  arranged  in  the  following  sequence: 

1.  Oxidases,  produce  their  action  with  the  help  of  free  oxygen. 

2.  Peroxidases,  hasten  the  formation  and  action  of  the  peroxids,  i.e.,  of  those 
easily  oxidizable  substances  which  take  up  molecular  oxygen  to  form  peroxids. 
These  organic  peroxids  produce  the  same  effects  as  hydrogen  peroxid,  from  which 
atomic  or  active  oxygen  is  removed  as  follows:  H2O2  =  H2O  +  O.  At  the 
present  time,  however,  no  evidence  is  at  hand  to  prove  that  hydrogen  peroxid 
is  actually  formed  in  the  tissues,  although  it  seems  that  it  is  produced  in  the  green 
leaves  of  plants  in  the  course  of  their  assimilation  of  carbon. 

3.  Perhydridase,  hastens  the  reduction  of  the  water-molecule  by  aldehyds. 
This  ferment,  therefore,  regulates  the  hydrolytic  cleavage  and  liberates  the  oxygen 
of  the  water. 

4.  Catalase,  changes  hydroperoxid  into  molecular  oxygen  and  water.  This 
substance  is  very  prone  to  be  formed  in  the  course  of  these  processes  either  in  a 
direct  way  or  from  peroxids.  It  would  eventually  destroy  life.  Consequently, 
this  ferment  really  serves  as  a  protection  to  the  cell,  because  it  causes  its  removal. 

The  power  of  the  cell  to  regulate  the  intensity  of  its  oxidations  is 
dependent  upon  its  faculty  of  producing  ferments  of  the  preceding 
types.  Secondly,  it  is  also  evident  that  the  action  of  the  cells  is 
specific,  because  several  of  these  ferments  affect  the  oxidation  of  only 
particular  substances.  For  this  reason,  special  names  have  been 
applied  to  them,  such  as  xanthinoxidase,  tyrosinase,  etc.  The  former, 
33 


514  RESPIRATION 

for  example,  accomplishes  the  oxidation  of  hypoxanthin  and  xanthin 
to  uric  acid,  while  the  latter  regulates  the  oxidation  of  tyrosin.  In 
this  connection,  mention  should  also  be  made  of  the  fact  that  oxidizing 
ferments,  or  oxidases,  are  widely  distributed  through  the  vegetable 
tissues.  Thus,  guaiaconic  acid  may  be  oxidized  by  the  latter  in  the 
presence  of  atmospheric  oxygen,  and  peroxid  of  hydrogen  is  not  needed 
by  them  to  color  guaiacum  blue.  Quite  similarly,  many  fungi  contain 
a  ferment  known  as  tyrosinase  which,  when  added  to  solutions  of 
tjn^osin  in  the  presence  of  air,  oxidizes  the  tyrosin  into  a  brown  pig- 
ment. The  brown  discolorations  upon  the  cut  surfaces  of  apples  and 
potatoes  are  attributed  to  the  oxidation  of  a  chromogen  by  the  oxygen 
of  the  air  under  the  influence  of  an  oxidase. 


CHAPTER  XLI 


THE  RESPIRATORY  INTERCHANGE  UNDER  DIFFERENT 

CONDITIONS 

The  Respiratory  Quotient. — The  quantity  of  air  respired  in  a  day 
amounts  to  about  11,000  liters.  In  a  man  weighing  70  kg.,  this  amount 
of  air  is  brought  into  relation  with  a  diffusion  surface  measuring  about 
90  sq.  m.,  so  that  1  kg.  of  substance  possesses  a  breathing  surface  of 
1.28  sq.  m.  A  person  of  this  weight  produces  under  ordinary  condi- 
tions about  250  c.c.  of  carbon  dioxid  for  each  kilogram  of  weight  in 
an  hour,  or  428  liters  in  the  course  of  a  day.  During  absolute  rest  or 
sleep  the  CO2  production  is  of  course  greatly  diminished,  amounting 
to  only  160  c.c.  in  an  hour.  Excessive  muscular  exercise,  on  the  other 
hand,  increases  it  considerably,  to  possibly  1200  c.c.  in  an  hour.  Fur- 
thermore, it  may  justly  be  assumed  that  the  production  of  85  c.c.  of 
carbon  dioxid  necessitates  the  absorption  of  100  c.c.  of  oxygen.  The 
relation  between  the  quantities  of  0  absorbed  and  GO2  liberated  dur- 
ing a  given  period  of  time  is  designated  as  the  respiratory^  quotient.^ 
Since  the  air  during  its  sojourn  in  the  lungs  loses  4.78  volume  per 
cent,  of  0  and  acquires  4.34  volume  per  cent,  of  CO2,  the  respiratory 

quotient  is:  -7c-  j^  =  0.901.     This  value,  however,  is  subject  to 
U     4.7o 

fluctuations,  because  the  amount  of  ox^^gen  required  to  oxidize  the 

carbon  seldom  remains  the  same  for  long  periods  of  time.     It  is  under 

the  constant  influence  of  such  factors  as:  species,  diet,  age,  temperature, 

muscular  activity  and  the  composition  of  the  inspired  air. 

The  respiratory  quotient  of  warm-blooded  animals  is  larger  (0.7  to  1.0)  than 
that  of  cold-blooded  animals  (0.65  to  0.75),  because  the  latter  consume  less  oxygen 
for  each  kilo  of  body-weight  than  the  former.     The  frog,  for  example,  possesses 

1  Zuntz,  Hermann's  Handb.  der  Physiol.,  iv,  90. 


RESPIRATORY  INTERCHANGE  UNDER  DIFFERENT  CONDITIONS  515 

an  oxygen  rcqulrcniont  of  only  0.07  i)cr  kilo  of  weight,  which  is  from  6  to  18  times 
smaller  than  that  of  dilTerent  species  of  warm-hlooded  animals.  When  considered 
in  a  relative  way,  it  also  holds  true  that  the  smaller  animals  display  a  mon;  intense 
respiratory  interchange  than  the  larger.  This  fact  may  readily  he  deduced  from 
the  following  compilation,  containing  the  oxygen  consumption  for  each  kilo  of 
weight:  in  the  horse  0.4;i7,  calf  0.48,  sheep  0.499,  ox  0.55,  rahl)it  0.92,  and  cat  1.00. 
This  rule  may  also  be  aj)plied  to  animals  of  the  same  species,  because  the  body- 
surface  of  the  smaller  ones  is  more  extensive  in  relation  to  their  l)ody-weight  than 
that  of  the  larger.  This  implies  that  the  loss  of  heat  is  j)roportionately  much  greater 
in  the  smaller  animals  and  mu.st  be  compensated  for  l)y  an  increase  in  their  metab- 
olism. This  in  turn  necessitates  a  greater  consumption  of  O  and  production  of 
C02.  Thus,  while  an  animal  weighing  2.1  kg.  gives  off  1.02  g.  of  CO^  for  each 
kilogram  of  weight  in  an  hour,  one  weighing  3.1  kg.   yields  only  1.96  g.  in  all. 

The  respiratory  quotient  is  higher  in  herbivora  (0.9  to  1.0)  than  in  camivora 
(0.7  to  0.8)  or  omnivora  (0.8  to  0.9).  These  differences  find  their  cause  in  the 
character  of  the  fno<t,  because  the  formation  of  CO2  from  carbohydrates,  upon 
which  herbivora  feed,  requires  the  use  of  all  the  O  for  the  reduction  of  the  molecules, 
while  the  H  has  already  acquired  an  amount  of  O  sufficient  to  satisfy  it.  During 
the  disintegration  of  the  fats  and  proteids,  on  the  other  hand,  a  portion  of  the  O 
is  employed  for  the  oxidation  of  the  H  to  form  H2O.  For  this  reason,  the  quotient 
is  lowered  by  a  diet  rich  in  proteid  material,  and  heightened  by  vegetable  foods. 
It  mu.st  approximate  unity  (1.0)  as  soon  as  a  sufficient  amount  of  carbohydrates 
has  been  ingested.    *For  example,  since  6  molecules  of  O  oxidize  1  molecule  of 

grape  sugar   (CeHioOe  =  6CO2  +  6H2O),  the  quotient  must  be  -/rpr-^  =  1.     In 

DU2 
the  case  of  the  fats  which  require  a  much  greater  number  of  molecules  of  O,  the 
quotient  must,  of  course,  become  smaller.     Olein,  for  example,  needs  80  molecules 
of  O  to  reduce  its  molecules,  as  follows: 

C3H5(Ci8H3302)3  =  57CO2  +  52H2O;  hence,  the  quotient  must  be  ^^^  = 

0UU2 
0.712. 

Inasmuch  as  the  proteins  vary  considerably  in  their  composition  and  are  not 
oxidized  in  their  entirety  in  the  body,  their  quotient  can  only  be  arrived  at  by 
calculation.  Thus,  it  has  been  estimated  that  this  value  in  the  case  of  albumin 
varies  between  0.75  and  0.81,  in  accordance  with  the  degree  of  disintegration  of 
the  substance.  During  periods  of  starvation  the  quotient  remains  below  normal, 
because  all  the  available  carbohydrates  have  been  utilized  and  the  body  subsists  on 
its  own  proteids  and  fats.  The  production  of  CO2  then  falls  off  at  a  greater  rate 
than  the  consumption  of  O.  In  diabetic  patients,  whose  consumption  of  carbo- 
hydrates is  at  a  minimum,  the  respiratory  quotient  is  very  low,  namely,  0.6  to  0.7. 
Hence,  it  will  be  seen  that  the  respiratory  quotient  at  any  given  moment  is  depend- 
ent upon  the  nature  of  the  substances  undergoing  oxidation.  Atwater  has  fur- 
nished   the   following   table: 

Starch 1.0 

Cane  sugar 1.0 

Glucose 1.0 

Animal  fat 0.711 

Protein 0.809 

In  hibernating  animals  the  quotient  becomes  very  small  (0.25),  because  the 
output  of  CO2  and  the  consumption  of  O  are  enormously  reduced,  but  the  former 
in  a  greater  measure  than  the  latter.  The  CO2  output  is  also  diminished  during 
sleep  and  more  so  than  the  intake  of  O.  The  quotient,  therefore,  becomes  smaller 
than  normal.  Brief  muscular  exercise,  on  the  other  hand,  increases  it  immediately, 
because  a  considerable  quantity  of  carbon  dioxid  is  then  washed  out  of  the  active 
tissues.  During  longer  periods  of  muscular  activity  the  quotient  remains  prac- 
tically the  same,  in  spite  of  the  fact  that  greater  amounts  of  CO2  and  O  are  worked 


516  RESPIRATION 

over.  On  a  mixed  diet,  however,  their  relationship  remains  practically  unaltered. 
The  ingestion  of  different  foodstuffs  changes  matters  considerably.  Thus,  the 
quotient  rises  to  1,  if  the  muscular  work  is  performed  exclusively  at  the  expense 
of  the  carbohydrate  material.  This  is  rarely  the  case,  although  muscular  work 
depends  chiefly  upon  the  carbohydrates,  because  these  bodies  are  more  immediately 
available  and  may  also  be  slowly  replenLshed  from  the  proteins.  The  fats  may  also 
be  drawn  upon,  but  since  there  is  no  evidence  at  hand  to  show  that  these  substances 
are  first  converted  into  carbohydrates,  it  must  be  concluded  that  the  muscles 
are  capable  of  utilizing  them  as  such.  Obviously,  therefore,  the  respiratory  quo- 
tient serves  as  a  reliable  index  of  the  oxidations  only  if  the  determinations  establish- 
ing its  value  have  been  extended  over  a  long  period  of  time.  Short  experiments 
may  lead  to  absolutely  erroneous  results  on  account  of  the  occurrence  of  accidental 
variations,  such  as  occasional  muscular  contractions  and  voluntary  changes  in  the 
depth  of  the  respiratory  movements.  ^  Even  the  mere  ingestion  of  food  may 
increase  the  gaseous  exchange,  because  it  augments  the  mechanical  and  secretory 
activities  of  the  alimentary  canal.  ^  None  of  these  influences  possess  a  permanent 
metabolic  value. 

Sex  and  age  influence  the  quotient  through  the  general  metabolism.  In  males 
the  average  CO2  output  is  greater  than  in  females,  but  this  general  difference 
between  the  sexes  is  not  in  evidence  if  persons  of  the  same  bodj'-weight  are  com- 
pared. The  influence  of  age  manifests  itself  by  the  low  value  of  the  quotient  in 
children  as  compared  with  that  of  adults.  Not  only  is  the  gaseous  interchange  in 
proportion  to  the  weight  greater  in  the  former,  but  more  O  is  being  absorbed  by 
them  in  comparison  with  the  COo  given  off.  Obviou.sly,  therefore,  the  child 
possesses  a  more  intense  metaliolism,  presumably  on  account  of  the  fact  that  its 
surface  in  proportion  to  its  weight  is  larger  than  that  of  the  adult,  thereby  entailing 
a  greater  loss  of  heat.  Aside  from  this  factor,  age  also  influences  the  respiratory 
interchange  because  the  tissues  gradually  become  less  active.  For  the  same  reason, 
the  respiratory  activity  is  greater  in  the  robust  than  in  the  weak  or  sick. 

Increases  in  the  external  temperature  tend  to  heighten  the  gaseous  interchange 
and  hence,  to  increase  the  quotient.  In  cold-blooded  animals,  in  particular,  the 
CO2  output  decreases  as  the  temperature  of  the  medium  falls  and  increases  as  the 
latter  rises.  In  warm-blooded  animals,  on  the  other  hand,  cold  within  physiolog- 
ical limits  has  a  tendency  to  stimulate  the  consumption  of  O  as  well  as  the  produc- 
tion of  COo.  Involuntary  muscular  tremors  (shivering)  increase  the  respiratory 
activity,  the  oxygen  intake  as  well  as  the  CO2  output  becoming  greater.  ^  "SMien 
the  body  temperature  rises,  as  in  fever,  the  respiratory  quotient  remains  at  first 
practically  the  same,  although  the  volumes  of  O  absorbed  and  CO-:  produced  are 
increased. 

The  rate  and  depth  of  the  respiratory  movements  do  not  appreciably  change  the 
relationship  of  the  O  and  CO2,  although,  to  begin  with,  the  more  ample  ventilation 
of  the  lungs  tends  to  heighten  the  CO2  output.  If  the  respiratory  amplitude  re- 
mains the  same  while  its  rate  is  increased,  the  volume  of  air  respired,  as  well  as  the 
absolute  quantity  of  CO2  discharged,  is  increased,  but  the  amount  of  CO2  in  com- 
parison with  the  total  volume  of  air  becomes  less.  Very  similar  results  are 
obtained  if  the  depth  of  respiration  is  increased  while  the  frequency  is  permitted 
to  remain  the  same.  Slow  and  deep  respirations,  of  course,  give  rise  to  a  greater 
discharge  of  CO^. 

The  composition  of  the  air  may  be  changed  considerably  before  the  gaseous 
interchange  is  markedly  altered,  because  a  variation  in  the  partial  pressure  of  the 
two  principal  gases  is  generally  compensated  for  by  changes  in  the  activity  of  the 
body  as  well  as  in  the  gas  content  of  the  blood.  This  compensation,  however,  has 
its  limits,  so  that  any  extraordinary  alteration  in  the  partial  pressures  of  the  gases 

1  Benedict  and  Cathcart,  Muse,  work,  etc.,  Carnegie  Institution  of  Washington, 
1913. 

2  Zuntz  and  Mehring,  Pflliger's  Archiv,  xxxii,  1883.  173. 

3  Speck,  Deutsch.  Arch,  fur  klin.  Med.,  xx.xiii,  1889,  375. 


RESPIRATORY  INTERCHANGE  UNDER  DIFFERENT  CONDITIONS  517 

of  the  atmospheric  air  must  finally  lead  to  a  serious  disturbance  of  the  normal 
metabolism.  The  conditions  to  be  dealt  with  at  thLs  time  are  a  decreased  and 
increased  supply  of  oxygen  and  an  increased  supply  of  carbon  dioxid.  In  all  these 
cases  we  are  concerned  with  changes  in  the  volume  per  cent,  of  the  gases. 

A  (limiindion  in  the  partial  pressure  of  the  oxygen  of  the  air  must  necessarily 
induce  a  similar  change  in  the  pressure  of  this  gas  in  the  alveoli.  But  inasmuch  as 
the  intensity  of  the  pulmonary  ventilation  and  the  magnitude  of  the  oxygen  con- 
sumption vary  almost  from  moment  to  moment,  a  direct  relationship  cannot 
exist  between  these  factors,  and  hence,  it  is  more  correct  to  speak  of  the  tension  of 
this  gas  in  the  alveoli  than  of  that  in  the  surrounding  air.  While  the  lower  limit 
of  the  former,  which  may  be  endured  without  danger  to  life,  differs  somewhat  in 
different  persons,  it  may  be  adjudged  at  30-3.5  mm.  Hg.  This  value,  of  course, 
holds  true  only  under  a  normal  atmospheric  pressure  and  corresponds  to  an  oxj-gen 
content  of  the  alveolar  air  of  4.5  per  cent.  Consequently,  provided  that  500  c.c. 
of  air  are  respired  17  times  in  a  minute,  an  altitude  of  5000  m.  may  be  attained 
before  the  oxygen  tension  in  the  alveoli  reaches  this  low  level.  ^  Any  difficulty 
arising  therefrom,  may  be  remedied  immediately  by  increasing  the  amplitude  of 
the  respiratory  movements.  This  change  augments  the  alveolar  tension  and  en- 
ables the  individual  safely  to  ascend  even  to  somewhat  higher  altitudes  if  he  reduces 
his  muscular  activity  to  a  minimum.  Paul  Bert-  places  the  lower  limit  of  the 
oxygen  pressure  of  the  outside  air  at  50  mm.  Hg,  which  corresponds  to  an  oxj-gen 
content  of  6  to  7  per  cent.  At  this  time,  the  total  atmospheric  pressure  amounts 
to  250  mm.  Hg.  An  animal  which  is  exposed  to  still  lower  tensions  develops  symp- 
toms of  dyspnea  and  convulsions  which  generally  terminate  fatally.  An  oxygen 
content  of  12  per  cent,  is  usually  endured  without  changing  the  quality  of  the 
respiratory  movements,  although  the  deficiency  in  oxygen  may  be  quite  apparent 
from  the  bluish  color  of  the  face. 

In  explaining  this  phenomenon  it  is  commonly  believed  that  an  alveolar  tension 
of  the  oxygen  of  about  30  mm.  Hg  causes  the  ox\-hemoglobin  to  be  dissociated 
so  rapidly  that  the  blood  is  no  longer  in  a  position  to  aerate  the  tissues  properly. 
Hence,  we  are  dealing  here  with  a  real  deficiency  in  the  oxygen  supply  which  is 
commonly  designated  as  anoxemia.  This  explanation  may  also  be  expressed  as 
follows:  We  know  that  for  physical  reasons  the  system  cannot  absorb  the  oxygen 
under  a  lower  tension  than  the  one  just  given.  Consequently,  the  350  c.c.  of 
oxygen  which  each  kilogram  of  substance  requires  in  an  hour  can  only  be  obtained 
with  a  differential  pressure  of  29  mm.  Hg  or  more.  If  the  pressure  falls  below  this 
value,  the  driving  force  behind  the  atoms  of  oxygen  becomes  so  slight  that  they 
cannot  traverse  the  alveolar  lining  to  enter  the  blood. 

An  increase  in  the  partial  pressure  of  the  oxygen  in  the  alveoli  can  be  attained 
either  by  the  inhalation  of  a  mixture  of  gases  which  is  rich  in  oxj-gen,  or  by  the 
inhalation  of  pure  oxygen  under  atmospheric  pressure.  But  even  if  this  gas  is 
supplied  in  a  pure  form,  so  that  its  pressure  is  increased  five  times,  namely,  from 
152  mm.  to  760  mm.  Hg,  no  considerable  variation  in  the  consumption  of  oxygen 
and  the  output  of  carbon  dioxid  results;  provided,  of  course,  that  the  experiment  is 
not  continued  for  an  unusually  long  time.  This  fact  tends  to  show  that  the  o.xida- 
tions  in  our  tissues  cannot  be  affected  in  a  favorable  manner  by  this  means  so  long 
as  physiological  conditions  prevail.  It  also  proves  that  the  atmospheric  air 
contains  an  amount  of  oxygen  which  is  more  than  sufficient  to  satisfy  our  needs. 
Any  variation  in  our  requirements  is  immediately  adjusted  by  changing  the  respira- 
tory rate  and  amplitude.  But  while  ordinarily  no  advantage  can  be  derived 
from  breathing  pure  oxygen,  this  procedure  may  prove  beneficial  in  those  diseases 
which  are  associated  with  pulmonary  infiltrations  and  a  poor  aeration  of  the  tissues. 
In  accordance  with  the  foregoing  discussion,  it  must  be  clear  that  all  we  can  hope  to 
accomplish  by  this  means  is  to  increase  the  driving  force  behind  the  atoms  of  oxygen, 

1  Loewy,  Respiration  und  Zirkulation  bei  Ander.  des  Sauerstoffgehalts  der 
Luft,  Berlin,  1895. 

*  La  pression  barometrique,  Paris,  1878. 


518  BESPIRATION 

and  to  impart  to  them  a  greater  penetrating  power.  In  this  way,  at  least  a  partial 
aeration  of  the  tissues  may  be  retained  for  some  time  after  the  respiratory  move- 
ments have  become  madequate,  or  after  the  alveolar  spaces  have  become  blocked 
by  exudated  material  (pneumonia).  Especially  beneficial  results  are  obtained 
in  certain  heart  diseases,  in  which  the  supply  of  oxygen  has  become  insufficient  on 
account  of  the  impairment  of  the  circulation.  The  oxygen  seems  to  exert  a  stimu- 
lating influence  upon  the  musculature  of  the  heart  m  consequence  of  which  its 
contractions  become  more  forceful. 

If  the  oxygen  is  inhaled  under  a  pressure  of  from  3  to  4  atmospheres,  it  acts  as 
a  poison,  death  resulting  in  the  course  of  a  short  time  from  respiratory  depression, 
loss  of  heat  and  a  general  intoxication.  The  same  effect  may  be  produced  by  the 
continued  inhalation  of  ordinary  air  under  a  pressure  of  from  15  to  20  atmospheres. 
It  has  also  been  shown  that  the  development  of  the  eggs  of  insects  is  greatly  re- 
tarded if  exposed  to  an  oxygen  pressure  of  less  than  one  atmosphere.  Fish  are 
killed  when  the  oxygen  content  of  the  water  is  raised  so  that  100  c.c.  contain  more 
than  10  volumes  of  dissolved  oxygen.  Quite  similarly,  it  was  found  by  Smith ^ 
that  mice  which  had  been  exposed  for  several  hours  to  an  oxygen  pressure  of  2 
atmospheres  acquired  a  subnormal  content  in  oxygen.     These  animals  then  exhib- 


FiG.  258. — Effect  of  CO2  on  Respiratory  Mo\^ments  of  Rabbit.     {Scott.) 
During  the  first  period  indicated  on  the  signal  line  the  animal  breathed  9.6  per  cent. 

CO2  in  air,  and  during  the  second  period  10  per  cent.  CO2  with  33  per  cent,  oxygen. 

Time  tracing  =  2  seconds. 

ited  inflammatory  changes  of  the  lining  cells  of  the  alveoli,  similar  to  those  ob- 
served in  pneumonia.  A  longer  exposure  to  this  gas  proved  fatal  in  a  few  days. 
Facts  such  as  these  unmistakably  prove  that  the  administration  of  oxygen  is  not 
at  all  without  danger. 

A  slight  increase  in  the  partial  pressure  of  the  carhon  dioxid  (to  5  per  cent.)  is 
reacted  against  as  a  rule  by  an  increase  in  the  respiratory  rate  and  amplitude 
(hyperpnea),  but  the  intensity  of  the  oxidations  is  not  materially  changed. ^  In 
those  cases  in  which  a  greater  output  of  carbon  dioxid  has  actually  been  observed, 
the  change  seems  to  be  due  to  the  greater  activity  of  the  muscles  of  respiration.  If 
the  carbon  dioxid  in  the  inspired  air  is  increased  to  8  or  10  per  cent.,  dyspnea  results; 
the  output  of  carbon  dioxid  is  diminished  and  later  on  also  the  intake  of  oxygen. 
A  further  increase  in  the  partial  pressure  of  this  gas  to  15  per  cent,  leads  to  an 
augmentation  of  these  conditions  until,  at  concentrations  of  from  30  to  40  per  cent., 
a  respiratory  depression  sets  in  which  is  soon  followed  by  the  death  of  the  animal. 
At  first,  therefore,  the  tendency  is  to  increase  the  ventilation  in  the  alveoli  by 
hyper  efforts  at  respiration  so  as  to  maintain  the  tension  of  this  gas  in  the  blood. 
This  change  is  accompanied  by  a  rise  in  blood  pressure  which  is  caused  in  part  by 
a  greater  cardiac  output  and  in  part  by  a  constriction  of  the  blood-vessels.  Later 
on,  however,  as  the  tension  of  the  carbon  dioxid  is  increased  to  15  per  cent.,  the 

1  Jour,  of  Physiol.,  xxii,  1898,  307. 

^  Speck,  Menschl.  Atmung.,  Leipzig,  1892. 


RESPIRATORY  INTERCHANGE  UNDER  DIFFERENT  CONDITIONS  519 

dyspnea  gradually  becomes  more  evident  until  it  eventually  gives  way  to  a  respira- 
tory and  circulatory  depression  similar  to  tliat  observed  in  deep  narcosis  (Fig.  259). 

Changes  in  Barometric  Pressure. — It  is  also  feasible  to  chan^;(i  the 
pressures  of  the  gases  by  altering  the  barometric  pressure.  This  can 
be  done  either  by  compressing  the  air  surrounding  us,  or  by  changing 
our  altitude.  Thus,  a  deficiency  in  oxygen  may  be  produced  either 
by  placing  an  animal  into  a  chamber  in  which  the  oxyget'  tension  is 
low  or  by  bringing  it  to  a  higher  altitude.  As  is  indicated  in  the  suc- 
ceeding table,  the  pressure  decreases  the  more,  the  higher  the  altitude. 


Fig.  259. — Record  of  the  Carotid  Blood-pressure  During  Dyspnea  (Dog). 
At  L  the  tracheal  tube  was  held  shut  until  the  blood -pressure  began  to  drop. 


Elevation  above  sea  level, 
m. 

Barometric  pressure, 
mm.  Hg 

Per  cent,  of  an 
atmosphere 

0 

760 

100 

1000 

670 

88 

2000 

693 

78 

3000 

524 

69 

4000 

463 

61 

5000 

410 

54 

6000 

357 

47 

7000 

320 

42 

Sojourns  in  rarefied  air  give  rise  to  a  complex  of  symptoms  which 
are  grouped  under  the  term  of  mountain  sickness.  A  person  affected 
in  this  way  suffers  from  headache,  nausea,  vertigo,  hemorrhages  and 
a  general  mental  and  bodily  apathy.  It  is  true,  however,  that  the 
altitude  at  which  these  symptoms  appear  is  not  the  same  for  all 
individuals,  because  a  process  of  adaptation  is  frequently  brought  into 
play  which  allows  the  continuance  of  normal  function  even  at  higher 


520  RESPIRATION 

altitudes.  Most  generally,  however,  an  elevation  of  about  4000  m. 
suffices  to  produce  definite  discomforts  and  especially  if  the  consump- 
tion of  oxygen  has  been  markedly  increased  on  account  of  the  muscular 
exertions  incurred  during  climbing.  At  a  height  of  5000  m.,  at  which 
the  pressure  of  the  air  is  reduced  to  about  one-half  and  the  oxygen 
tension  to  about  11  per  cent,  of  an  atmosphere,  scarcely  anybody 
escapes  the  sensations  of  fatigue  and  respiratory  oppression.  Neither 
is  it  possible  to  obviate  these  difficulties  by  ascending  to  these  heights 
in  a  balloon,  because  even  in  the  absence  of  all  unnecessary  muscular 
activity,  the  body  is  in  need  of  more  oxygen  owing  to  an  increased 
action  of  the  heart  and  a  compensatory  augmentation  of  the  cellular 
oxidations.  More  favorable  conditions,  however,  may  be  established 
during  balloon  ascensions,  and  hence,  somewhat  higher  altitudes  may 
be  attained  in  this  way.  Altitudes  of  7000-8000  m.  and  over  may  be 
reached  by  resorting  to  inhalations  of  pure  oxygen,  but  even  this  arti- 
ficial means  does  not  afford  an  absolute  protection  against  the  develop- 
ment of  dangerous  conditions.  This  is  shown  by  the  experiences 
which  Tissandier^  had  while  ascending  in  a  balloon  to  a  height  of 
8600  m.  At  an  altitude  of  7500  m.  he  and  his  two  companions  became 
so  weak  that  they  could  not  make  effective  use  of  the  oxygen  bags. 
All  three  persons  finally  lost  consciousness  but  without  having  pre- 
viously experienced  a  decided  dyspnea.  Tissandier  was  the  only 
survivor. 

Henderson^  and  his  collaborators  have  produced  acute  effects  of 
oxygen  deficiency  at  sea-level  by  breathing  into  an  apparatus  con- 
sisting of  a  spirometer  and  a  canister  containing  alkali.  The  exhaled 
carbon  dioxid  is  absorbed  by  the  alkali,  while  the  oxygen  is  gradu- 
ally diminished  by  the  continual  rebreathing.  The  increase  in  the 
frequency  of  the  heart  is  slight  at  first,  only  about  one  to  three  beats, 
but  a  marked  acceleration  sets  in  when  the  oxygen  has  fallen  to  be- 
tween 13  and  9  per  cent.  (14,500  to  22,000  feet  of  altitude).  In  men 
who  do  not  tolerate  low  percentages  of  oxygen  an  increase  of  from 
40  to  70  beats  was  not  uncommon.  The  systolic  blood  pressure  re- 
mains about  the  same  until  the  oxygen  has  been  lowered  to  between 
14  and  9  per  cent.,  when  it  may  rise  15  to  20  mm.  Hg  above  normal. 
The  diastolic  pressure  remains  fairly  normal,  but  falls  somewhat 
after  the  oxygen  has  been  reduced  to  9.5  per  cent,  or  less.  The  best 
type  of  men  may  tolerate  as  low  an  oxygen  content  as  G  per  cent., 
which  corresponds  to  an  altitude  of  close  to  30,000  feet.  The  hemo- 
globin showed  a  well  defined  increase  in  at  least  25  per  cent,  of  all 
the  men.  No  cardio-  vascular  lesions  could  be  noted  in  men  in 
"optimum"  condition;  others,  on  the  other  hand,  developed  mur- 
murs and  hypertrophic  conditions. 

In  accordance  with  Bert,  it  is  generally  held  that  the  disturbances 
just  described,  are  due  to  a  failure  of  the  diffusion  pressure  which 

1  La  nature,  1875,  337. 

'^  Medical  Studies  in  Aviation,  Jour.  Am.  Med.  .Assoc,  Ixxi,  1918. 


RESPIKATOllY   IXTEKCHANGE  UNDER  DIFFERENT  CONDITIONS  521 

quickly  induces  a  lack  of  oxygon  in  the  system,  commonly  called 
anoxemia.  This  view  has  foanil  exiierimental  j)roof  in  the  work  of 
Ziint  z  and  others,  who  luive  shown  that  the  oxyj^en  tc^nsion  in  the  alveoli 
is  diminished  at  high  altitudes.  Upon  Monte  Rosa,  for  example,  the 
different  members  of  his  party  showed  tensions  of  only  37-57  mm.  Hg 
and  all  suffered  from  mountain  sickness.  In  this  connection  attention 
should  ])riefly  be  called  to  the  fact  that  the  number  of  the  erythrocytes 
increases  at  high  altitudes,  but  clearly, even  this  change  must  eventually 
fail  in  its  purpose  for  the  reason  that  the  tension  of  this  gas  finally 
reaches  so  low  a  level  that  it  cannot  enter  in  sufficiently  large  qvian- 
tities.  The  hemogloljin  remains  below  its  point  of  saturation.  As  a 
result  of  this  scarcity  of  oxygen,  the  heart  muscle  weakens  and  even- 
tually fails  to  sustain  the  circulation.  The  nervous  tissue  is  then 
unable  to  effect  a  proper  coordination  of  the  muscular  movements. 
Provided,  however,  that  a  certain  limit  has  not  been  exceeded,  these 
symptoms  disappear  in  the  course  of  time  and  the  individual  finally 
acquires  a  muscular  force  as  great  as  that  previously  shown  by  him 
upon  the  plains.  This  adaptation  is  dependent  upon  the  production 
of  acid  substances,  especially  lactic  acid  and  carbon  dioxid,  which 
exert  a  stimulating  action  upon  the  respiratory  center  and  augment 
the  ventilation  in  the  lungs. 

Mosso^  has  submitted  a  somewhat  different  explanation  which  is 
based  upon  a  diminution  in  the  carbon  dioxid  tension  of  the  blood, 
constituting  the  condition  of  acapnia:  The  claim  is  made  that 
mountain  sickness  is  associated  with  an  excessive  loss  of  carbon  dioxid 
in  consequence  of  which  the  tissues  themselves  are  impoverished.  We 
know,  however,  that  acapnia  may  be  present  in  individuals  without 
that  the  disorders  just  mentioned  develop,  and  besides,  this  condition 
may  be  absent  during  the  most  acute  stage  of  mountain  sickness. 
It  also  happens  at  times  that  these  symptoms  appear  sometime  after 
the  individual  has  again  reached  the  plains.  These  facts  tend  to  show 
that  the  real  difficulty  is  more  deeply  seated  and  must  be  sought  for 
in  a  disorder  of  the  tissue  oxidations. 

Higher  barometric  pressures  are  encountered  in  submarine  work, 
such  as  is  required  during  the  building  of  tunnels  and  caissons.  It  has 
previously  been  mentioned  that  pressures  of  5  to  6  atmospheres  cannot 
be  endured  for  any  length  of  time  without  serious  consequences  and 
that  a  pressure  of  15  atmospheres  brings  on  convulsions  and  death. 
But,  since  a  depth  of  10  m.  corresponds  to  an  increase  in  pressure  of 
only  1  atmosphere,  the  human  body  will  rarely  be  called  upon  to  endure 
a  pressure  of  more  than  2  or  3  atmospheres.  In  descending  to  this 
depth  it  is  imperative  to  proceed  slowly,  and  to  permit  the  sj'stem  to 
become  adapted  first  to  intermediate  degrees  of  pressure  before  the 
chamber  of  greatest  pressure  is  entered.  Quite  similarly,  it  is  abso- 
lutely necessary  to  proceed  slowly  with  the  decompression,  because 
any  abrupt  cessation  of  the  pressure  is  prone  to  produce  a  complex  of 
^  Der  Mensch  auf  den  Hochalpen,  Leipzig,  1899. 


\* 


522  KESPIRATION 

symptoms  which  constitute  the  so-called  caisson  disease,  ^  or,  as  the  work- 
men call  it,  the  "bends."  The  muscles  and  joints  become  painful  and  a 
degree  of  dyspnea  develops  which  leads  to  cyanosis,  congestion, 
vertigo  and  unconsciousness.  In  many  cases  certain  groups  of  mus- 
cles become  paralyzed,  giving  rise  to  the  condition  commonly  de- 
scribed as  "diver's  palsy."  These  symptoms  are  attributed  as  a 
rule  to  an  evolution  of  nitrogen.  Obviously,  the  absorption  of  this 
gas  by  the  tissues  increases  with  the  pressure,  but  if  the  pressure  is 
then  suddenly  released,  the  rapidly  escaping  bubbles  of  this  inert  gas 
collect  in  large  numbers  in  the  capillaries  and  cause  a  blocking  of  the 
blood-flow  and  a  loss  of  function  of  the  parts  situated  distally  to  the 
obstruction.  In  fact,  it  is  conceivable  that  the  rapid  evolution  of  this 
gas  may  lead  to  an  actual  destruction  of  the  soft  nervous  structures 
and  a  loss  of  function  of  the  structures  innervated  by  them. 

The  Gaseous  Composition  of  the  Blood  under  Different  Conditions. 
Eupnea. — If  the  quantities  of  0  and  CO2  in  the  blood  vary  within 


Fig.  260. — Stethographic  Record  of  the  Respiratory  Movements. 
E,  eupnea;  A,  apnea  produced  by  taking  three  or  four  deep  breaths. 

normal  limits,  the  animal  is  said  to  be  in  the  state  of  eupnea.  The 
respiratory  movements  exhibit  during  this  period  a  normal  amplitude 
and  frequency. 

Apnea. — An  animal  may  be  placed  in  the  condition  of  apnea 
in  two  ways,  namely,  by  increasing  the  frequency  of  its  respiratory 
movements  or  by  permitting  it  to  breathe  pure  oxygen.  It  is  a  matter 
of  common  experience  that  the  taking  of  two  or  three  deep  breaths  in 
rapid  succession  forces  us  to  suspend  our  respiratory  activity  for  a 
short  period  of  time  (Fig.  260).  Quite  similarly,  the  quickly  repeated 
inflation  of  the  lungs  of  a  tracheotomized  animal  causes  it  to  cease  its 
respiratory  movements  temporarily.  The  inhalation  of  pure  oxygen 
gives  rise  to  the  same  effect.  As  far  as  the  character  of  the  respiratory 
motions  is  concerned,  apnea  signifies  a  temporary  cessation  of  these 
movements.  With  reference  to  the  condition  of  the  blood,  several 
views  have  been  advanced.  Thus,  it  has  been  thought  that  this  respira- 
tory inhibition  is  dependent  upon  an  overoxygenation  of  the  blood, 

1  Hill,  Caisson  Sickness,  London,  1912. 


RESPIRATORY  INTERCHANGE  UNDER  DIFFERENT  CONDITIONS  523 

this  inhibition  lasting  until  the  extra  amount  of  oxygon  has  again  been 
used  up.  Head/  however,  has  shown  that  this  effect  may  also  be 
obtained  by  inllating  the  lungs  with  piu'e  hydrog<'n,  altliough  it  is  true 
that  the  apneic  cessation  of  res])iration  is  then  briefer  in  its  duration 
and  may,  in  fact,  be  abolished  altogether.  Besides,  it  should  be  men- 
tioned that  the  contention  of  Ewald,  that  in  apnea  the  blood  is  actually 
oversaturated  with  oxygen,  has  been  disproved  by  Hopp(vSeyler.2 
It  seems,  therefore,  that  some  other  factor,  besides  the  oxygen,  must 
be  responsible  for  this  phenomenon.  It  has  been  suggested  that  the 
repeated  distention  of  the  lungs  acts  as  an  excitant  to  the  receptors 
of  the  vagi  nerves,  in  consequence  of  which  impulses  are  generated 
which  reficxly  inhibit  the  inspiratory  discharges  from  th(;  respiratory 
center.*  A  more  plausible  explanation,  however,  is  the  one  offered  by 
Mosso,^  which  states  that  any  excessive  ventilation  of  the  hmgs  induces 
a  scarcity  of  carbon  dioxid  (acapnia)  which  eventually  leads  to  a  con- 
dition of  subnormal  stimulation  of  the  respiratory  center.  The  re- 
spiratory actions  then  cease  until  the  accumulation  of  carbon  dioxid 
in  the  blood  has  again  been  raised  to  normal.  That  this  is  so  may  be 
gathered  from  the  fact  that  augmentations  of  the  respiratory  move- 
ments fail  absolutely  to  produce  the  apneic  standstill  if  the  carbon 
dioxid  content  of  the  inspired  air  is  retained  at  4.5  per  cent.  In  order 
to  account  for  the  different  discrepancies  just  enumerated,  it  has  been 
suggested  to  recognize  three  types  of  apneas,  namely: 

Apnea  vera,  which  is  due  to  the  lowering  of  the  CO2  content, 

Apnea  vagi,  which  is  caused  by  the  stimulation  of  the  inhibitor  fibers  of  the 

vagi  nerves,  and 

Apnea  spuria,  which  is  dependent  upon  stimulations  from  other  parts  of  the 

body. 

As  an  example  of  the  first  type  might  be  mentioned  the  apnea  fetalis, 
i.e.,  the  permanent  inhibition  of  the  respiratory  activity  of  the  young 
while  in  the  uterus.  As  an  example  of  the  second  type  may  serve  the 
rather  temporary  inhibition  following  the  distention  of  the  lungs  by 
air  or  inert  gases,  and  as  an  example  of  the  third  type,  the  cessation 
of  respiration  exhibited  by  diving  animals  as  soon  as  their  nares  or 
beaks  are  brought  in  contact  with  water. 

A  very  peculiar  type  of  respiration  is  frequently  observed  during 
such  pathological  states  as  arteriosclerosis,  uremic  coma,  anemia, 
increased  intracranial  pressure  and  lesions  of  the  central  nervous 
system.  The  respiratory  movements  then  occur  in  groups  which  are 
separated  from  one  another  by  apneic  pauses.  This  condition  of 
periodic  breathing  is  commonly  designated  as  Cheyne-Stokes  respira- 
tion (Fig.  261).  The  periodicitj^  of  these  movements,  however,  is  not 
the  same  in  all  cases;  but  whether  only  ten  or  forty  of  them  appear 

1  Jour,  of  Physiol.,  x,  1889,  1. 

2  Zeitschrift  fur  physiol.  Chemie,  iii,  1879,  105. 

3  Miescher-Rusch,  Wiener  Akad.,  Ixxxv,  1882,  101. 

4  Arch.  ital.  de  biol.,  xl,  1903. 


524 


RESPIRATION 


together,  the^jEirst  respirations  of  each  group  always  begin  small  and 
gradually  increase  in  amplitude  until  their  maximum  has  been  reached. 
Subsequent  to  this  point  they  again  decrease  slowly  to  complete  stop- 
page. The  intervening  respiratory  standstills  may  last  only  a  few 
seconds  or  a  longer  time,  say,  30-40  seconds.  As  Eyster^  has  shown, 
these  variations  in  the  respirations  are  accompanied  by  rhythmic 
changes  in  the  blood  pressure,  a  rise  occurring  most  generally  toward 
the  end  of  the  apneic  phase,  at  which  time  the  oxygen  tension  of 
the  alveolar  air  is  greatly  diminished.  The  succeeding  respirations, 
therefore,  would  be  incited  by  a  lack  in  oxygen.  Pembrey,'^  on  the 
other  hand,  advocates  the  view  that  the  apneic  phase  is  caused  by  a 
diminution  in  the  carbon  dioxid  tension  which  leaves  the  respiratory 
center  temporarily  without  its  normal  stimulus.  At  all  events,  it  is 
possible  to  remove  this  condition  for  a  time  by  the  administration  of 
either  oxygen  or  carbon  dioxid.     The  former  tends  to  heighten  the 


Fig.  261. — Tracing  Showing  the  Cheyne-Stokes  Form  of  Respiration.     (Hill.) 


irritability  of  the  respiratory  center,  whereas  the  latter  stimulates  it 
until  it  again  discharges  its  impulses. 

A  similar  type  of  respiration  is  frequently  observed  during  sleep 
and  in  meningitis,  in  which  disease  it  constitutes  an  unfavorable 
prognostic  sign.  It  is  known  as  Biot  's  respiration  and  consists  of 
rapid  short  breathing  which  is  interrupted  by  pauses  lasting  from 
several  seconds  to  half  a  minute. 

Htj'per'pnea. — This  condition  is  characterized  by  a  moderate  in- 
crease in  the  respiratory  rate  and  amplitude.  It  is  attributed  as  a 
rule  to  a  diminution  of  the  oxygen  and  an  increase  of  the  carbon  dioxid 
occurring  in  the  course  of  heightened  muscular  activity.  Besides  the 
carbon  dioxid,  it  is  entirely  probable  that  other  fatigue  substances  are 
present  which  act  as  powerful  exciting  agents  of  the  respiratory  center. 
It  is  also  possible  to  augment  the  respiratory  activity  in  an  indirect 
manner  by  stimulating  the  receptors  for  touch,  pain  and  temperature. 
A  reaction  of  this  kind  is  usually  experienced  upon  tactile  impressions, 
as  well  as  upon  the  immersion  of  the  body  in  water  of  32°  C.  or  in 
water  charged  with  carbonic  acid  gas.     It  can  also  be  produced  by 

1  Jour,  of  Exp.  Med.,  viii,  1906,  565. 

2  Jour,  of  Path,  and  Bact.,  xii,  1908,  258. 


RESPIRATORY  INTERCHANGE  UNDER  DIFFERENT  CONDITIONS  525 

exposing;  an  animal  to  a  high  tompcratiiro  or  by  heating  its  l)loo(l 
directly  as  it  traverses  the  carotid  artery.^  These  typ(^s  of  hyperpnea, 
howcn-er,  are  not  de])endent  upon  the  gaseous  coini>osition  of  the  blood 
and  should,  therefore,  be  classihed  as  ordinary  reilex  reactions. 

Dyspnea. — If  prolonged,  the  condition  of  hyperpnea  gradually 
passes  over  into  the  condition  of  dyspnea,  the  essential  characteristic 
of  which  is  labored  breathing.  Its  cause  lies  either  in  a  defici(uicy  of 
oxygen  or  in  an  excess  of  carbon  dioxid;  most  generally,  however, 
these  two  factors  act  in  unison.  In  accordance  with  this  statement, 
it  must  be  evident  that  an  animal  may  be  rendered  dyspneic  in  two 
ways,  viz.,  by  interfering  with  its  respiratory  activity  in  a  mechanicuil 
way  or  by  altering  the  composition  of  the  inspired  air.  Among  the 
former  occurrences  might  be  mentioned  the  partial  occlusion  of  the 
respiratory  passage  by  foreign  bodies  or  by  pressure  from  without. 
In  a  chemical  way,  dyspnea  may  be  produced  either  by  lessening  the 
tension  of  the  oxygen  or  by  increasing  the  tension  of  the  carbon  dioxid. 
The  former  is  designated  as  O  =  dyspnea,  and  the  latter  as  COo  = 
dyspnea.  An  animal  may  also  be  rendered  dyspneic  by  permitting 
it  to  breathe  an  indifferent  gas,  such  as  pure  nitrogen  or  hydrogen. 
Curiously  enough,  the  dyspnea  then  ensuing  cannot  be  prevented  by 
lessening  the  carbon  dioxid  tension  of  the  blood,  which  would  natu- 
rally diminish  the  excitation  of  the  respiratory  center.  It  is  also 
possible  to  render  an  animal  dyspneic  by  permitting  it  to  inhale  an 
increased  amount  of  carbon  dioxid.  In  this  case,  the  oxygen  cannot 
be  the  deciding  factor,  because  the  occurrence  of  this  dyspnea  cannot 
be  prevented  by  simultaneously  raising  the  tension  of  this  gas.  De- 
ficiencies in  oxygen,  which  finally  give  rise  to  dyspnea,  may  be  pro- 
duced by  bleeding,  by  the  fixation  of  the  hemoglobin  by  carbon  mon- 
oxid,  by  hemolysis  of  the  red  corpuscles,  and  by  any  impairment  of 
the  cardiovascular  system  tending  to  lessen  the  vascularity  of  the 
tissues. 

While  the  general  picture  of  dyspnea  always  remains  the  same, 
certain  differences  may  nevertheless  be  noted  which  allow  us  to  differ- 
entiate the  O  =  dyspnea  from  the  CO2  =  dyspnea.  The  former 
usually  runs  a  longer  course  and  finally  leads  to  marked  motor  disturb- 
ances. The  latter,  on  the  other  hand,  immediately  assumes  a  more 
depressive  and  more  narcotizing  character.  Moreover,  during  the 
former  the  respirations  are  prone  to  be  rather  frequent  and  display  a 
forced  inspiratory  character,  whereas  during  the  latter  they  are  slow 
and  of  a  pronounced  expiratory  type. 

Asphyxia. — This  condition  represents  the  final  state  of  dyspnea,  a 
state  of  functional  exhaustion  and  collapse.  It  signifies  that  the 
deprivation  of  oxygen  has  been  completed.  The  powerful  respiratory 
movements  ordinarily  observed  during  the  later  stages  of  dyspnea, 

'  Fick  and  Goldstein,  Verhandl.  nlath.-natuI•^v.  Ges.,  Wurzburg,  ii,  156.  The 
term  polypnea  has  been  applied  to  this  form  of  hyperpnea  by  Richet,  Compt. 
rend.,  xcix,    1884,   279. 


526  RESPIR-^TION 

presently  give  way  to  infrequent  convulsive  efforts  and  these  in  turn 
to  slow  and  shallow  respirations  and  finally  to  mere  spasmodic  twitches. 
At  this  time,  the  pupils  are  markedly  dilated,  the  reflexes  are  extinct, 
the  integument  is  cyanosed,  and  the  extremities  stiffened.  The  urine 
and  feces  are  voided  generally  before  the  heart  has  ceased  to  beat. 
The  blood  pressure  rises  during  the  early  stage  of  dyspnea,  but  falls 
gradually  as  soon  as  the  respiratory  and  cardiac  depression  has  set  in. 
Inasmuch  as  the  heart  usually  continues  to  beat  for  several  minutes 
after  the  cessation  of  respiration,  it  is  still  possible  at  this  time  to 
resuscitate  the  animal. 

Ventilation. — The  problem  of  ventilation  Is  essentially  a  physio- 
logical one  and  has  to  do  primarily  with  the  chemical  properties  of  the 
respirator^'  air,  and  secondarily  with  its  temperature  and  its  content 
in  water  vapor.  Consequently,  ventilation  pro^■ides  not  only  for  a 
continuous  supply  of  pure  air  in  place  of  that  ^'itiated  with  the  products 
of  metaboKsm.  but  also  of  air  possessing  a  stimulating  temperature  and 
a  content  in  aqueous  vapor  in  keeping  with  the  physiological  require- 
ments of  the  body.  An  undue  emphasis,  however,  should  not  be  placed 
upon  any  one  of  these  factors  at  the  expense  of  the  others. 

Ventilation  does  not  purpose  to  bring  outdoor  conditions  indoors, 
but  simply  to  make  indoor  conditions  fit  for  indoor  life.  As  far  as  the 
composition  of  the  air  is  concerned,  we  know  that  an  adult  person  in- 
spires about  500  c.c.  of  air  seventeen  times  in  a  minute  and  that  his 
output  of  CO2  at  rest  amounts  to  17  liters,  or  to  0.68  cubic  feet  in  an 
hour.  During  gentle  exertion  this  value  rises  to  0.9  and  during  actual 
work  to  1.8  cubic  feet  per  hour.  Assuming  then  that  the  normal 
amoimt  of  COo  is  0.03  per  cent.,  the  percentage  of  this  gas  in  1000 
cubic  feet  (28,000  Hters)  of  air  will  be  increased  to  about  0.1  percent, 
in  the  com*se  of  an  hour.  Obviously,  therefore,  the  amount  of  fresh 
air  required  per  hour  to  keep  the  CO2  at  0.06  per  cent.,  is  0.03  :  0.6  :: 
100  -.xoTX  =  2000  cubic  feet.  If  the  normal  amount  of  CO2  is  reckoned 
at  0.04  per  cent.,  3000  cubic  feet  must  actually  be  pro\'ided  for,  but 
naturally,  this  amount  may  be  supplied  in  three  lots  of  1000  cubic 
feet  each.  Furthermore,  an  allowance  must  be  made  for  the  weight 
of  the  person,  because  a  woman  of  120  pounds  exhales  only  0.6  cubic 
feet  of  COo  in  an  hour  and  a  child  of  80  pounds  only  0.4  cubic  feet.  It 
is  also  essential  to  take  account  of  the  type  of  work  to  be  performed  by 
these  indi\'iduals. 

In  regard  to  O2,  little  need  be  .said,  because  even  in  the  worst  ven- 
tilated spaces  the  air  seldom  approaches  a  basis  of  15  volumes  per  cent., 
at  which  respiration  can  still  go  on  undisturbedly.  Hence,  we  are 
chiefly  concerned  at  this  time  with  the  CO2  content  of  the  respired  air, 
but  its  value  should  serv^e  merely  as  a  working  unit  to  indicate  the 
degree  of  \'itiation  of  the  air,  because  even  in  the  worst  ventilated  rooms 
it  is  rarely  present  in  amounts  sufficient  to  exert  a  pernicious  influence. 
Ordinar}^  increases  are  endured  for  some  time  without  discomfort, 
provided  that  the  temperature  and  the  humidity  of  the  air  remain 


RESPIILVTORY  INTERCHANGE  UNDER  DIFFERENT  CONDITIONS  527 

low.  Toward  larfi;or  amounts  of  CO...,  tho  systom  vory  readily  roacts 
by  a  greater  respiratory  ratc^  and  anii)litude  and  ot.luM-  (;lKinjj!;(!s.  Thus, 
if  it  is  said  that  the  air  of  a  nxjni,  in  wiiich  more  tliaii  0.07  vohimo 
per  cent,  of  CO2  is  ])resont,  feels  distinctly  close  and  uncomfortable. 
This  sensation  should  not  be  referred  to  a  deficiency  of  O  nor  to  a  super- 
fluity of  CO2,  but  rather  to  its  t(nnperature,  its  himiidity,  and  its  con- 
tent in  volatile  odorous  substances  and  dust. 

In  poorly  ventilated  rooms  the  COo  may  reach  0.30  volume  per 
cent.,  and  in  crowded  lecture  halls  0.80  volume  per  cent.,  but  the  dis- 
comfort experienced  in  places  of  this  kind  may  be  lessened  consider- 
ably either  by  lowering  the  tempcn-atiwe  and  the  humidity  of  the  air  or 
by  fanning  it.  Even  in  rooms  in  which  the  CO2  content  is  1.0  or  2.0 
per  cent.,  no  discomforts  are  experienced  so  long  as  the  aqueous  vapor 
and  the  temperature  are  kept  low,  but  these  facts  are  not  cited  to 
minimize  the  importance  of  the  composition  of  the  air,  but  solely  to 
show  that  the  other  two  factors  play  an  important  part.  In  a  general 
waj^  it  may  be  stated  that  optimum  conditions  prevail  when  the  tem- 
perature of  the  room  is  between  65°  and  68°  C,  and  when  the  moisture 
equals  50  to  75  per  cent,  relative  humidity.  The  air  itself  should  not 
contain  more  than  0.06  per  cent,  of  CO2  and  should  be  as  free  as  pos- 
sible from  bacteria,  gaseous  admixtures  and  dust.  If  it  contains 
more  than  this  amount,  artificial  means  should  be  resorted  to  to  renew 
it  with  a  frequency  which  is  to  be  determined  by  calculation  from  the 
proportion  of  CO2  per  volume  of  air. 

It  seems,  therefore,  that  the  injurious  consequences  of  living  in 
poorly  ventilated  quarters  are  cavised,  at  least  to  some  extent,  by  the 
physical  qualities  of  the  respired  air,  but  precisely  in  what  respect  a 
hot  and  humid  atmosphere  proves  harmful,  has  not  been  fully  deter- 
mined. Hermanns^  has  found  that  the  temperature  of  persons  living 
in  very  restricted  quarters,  rises  considerably,  and  furthermore,  the 
results  of  the  New  York  State  Commission  on  Ventilation^  indicate 
that  a  high  temperature  and  high  humidity  give  rise  to  an  elevation 
of  the  systolic  and  diastolic  pressures,  as  well  as  to  a  diminution  of  the 
vascular  tonus  and  a  lowering  of  the  resistance  of  the  body  against 
bacterial  infections.  The  general  disinclination  to  exercise  experienced 
at  this  time,  seems  to  have  a  deeply  seated  cause,  because  the  muscles 
themselves  are  incapable  of  performing  a  normal  amount  of  work. 
Lee  and  Scott^  have  shown,  that  a  loss  of  blood  sugar  results  at  this 
time  which  under  extreme  conditions  may  equal  5  per  cent,  of  normal. 

^  Archiv  fiir  Hj^giene,  i,  1883,  1. 

2  Lee,  Science,  N.  S.,  xliv,  1916,  183. 

3  Am.  Jour,  of  Physiol.,  xl,  1916,  486. 


528 


RESPIRATION 


CHAPTER  XLII 
THE  NERVOUS  REGULATION  OF  RESPIRATION 

The  Respiratory  Center  and  Its  Nervous  Connections. — The  nerv- 
ous mechanism  concerned  in  respiration,  consists  of  a  center  and 
different  efferent  and  afferent  conducting  paths.  On  the  efferent  side 
the  nerve  paths  always  remain  the  same,  because  the  same  muscles 
are  constantly  at  work  expanding  the  lung  and  producing  related  motor 
effects.  The  impulses  generated  in  the  respiratory  center,  reach  these 
different  effectors  by  way  of  their  respective  nerves,  and  hence,  the 
efferent  half  of  the  respiratory  arc  is  formed  by  the  different  nerves 
innervating  •  the  muscles  ordinarily  concerned  in 
respiration.  On  the  afferent  side,  on  the  other 
hand,  conditions  are  not  so  simple,  because  the 
character  of  the  respiratory  movements  is  subject 
to  variations  in  consequence  of  a  very  large  number 
of  sensory  impressions.  Practically  any  one  of 
the  receptors,  internal  as  well  as  external,  may  be 
the  recipient  of  impressions  which  are  eventually 
relayed  to  the  respiratoiy  center,  where  they  incite 
an  alteration  in  the  rate  and  depth  of  the  respira- 
tions. In  accordance  with  this  brief  preliminary 
statement,  it  should  be  evident  that  the  destruction 
of  the  efferent  paths  must  entail  an  immediate 
arrest  of  the  respiratory  movements,  because  the 
impulses  generated  by  the  respiratory  center,  are 
then  no  longer  able  to  reach  the  respiratory  mus- 
cles. An  arrest  of  respiration  must  also  follow  the 
destruction  of  the  center  itself,  for  the  reason  that 
the  stimuli  upon  which  the  contraction  of  these 
muscles  depends,  then  fail  to  materialize.  Con- 
trary to  these  results,  the  division  of  the  afferent 
path  does  not  stop  the  respiratory  movements, 
because  it  does  not  destroy  the  rhythmic  discharges  from  the  center. 
It  is  to  be  noted,  however,  that  the  movements  are  then  wholly  de- 
pendent upon  the  automatic  activity  of  the  center  and  can  no  longer 
be  varied  by  afferent  impulses  arising  in  other  parts  of  the  body. 

The  Location  of  the  Respiratory  Center. — In  accordance  with  the 
experiments  of  Lorry, ^  Le  Gallois^  and  riourens,^  the  respiratory  cen- 
ter is  situated  in  the  medulla  oblongata  at  the  level  of  the  apex  of  the 
calamus   scriptorius.     More  recent  experiments  by   Volkmann   and 

1  Memoires  pres.  a  I'acad.  des  Sciences,  i,  iii,  366. 
^  Exper.  sur  la  principe  de  la  vie,  Paris,  1812. 
^  Rech.  exp.  sur  la  systeme  nerveaux,  Paris,  1824. 


Fig.  262.— The 
Nervous  Regulation 
OF  Respiration. 

C,  respiratory 
center  is  under  the 
control  of  afferent 
impulses  (A)  from 
different  receptors 
(R).  On  the  efferent 
side  (E)  it  is  in  con- 
nection with  the  dif- 
ferent muscles  of  res- 
piration (M). 


THE    NERVOUS    REGULATION    OF    RESPIRATION  529 

others  have  shown  that  it  is  possible  to  make  a  median  incision  through 
tliis  structure  witliout  destroyinfj;  the  respiratory  movciments.  For  tliis 
reason,  the  centtn-  is  said  to  he  l)ihiteral,  eacli  half  l)(>inp;  cspc^cially 
concerned  with  the  nuisck^s  situated  on  the  corres])onding  side  of  the 
thorax.  In  this  connection  brief  reference  should  also  be  made  to  the 
fact  that  injuries  to  the  cerebral  cortex  (hemiplegia)  most  generally 
leave  the  respiratory  musculature  unafTected.  This  is  especially  true 
of  the  diaphragm  and  the  intorcostals.  It  seems,  therefore,  that  these 
muscles,  besides  being  governed  by  lower  centers,  possess  a  bilat- 
eral representation  in  the  motor  cortex  of  the  cerebrum.  Conse- 
quently, the  destruction  of  one  motor  area  cannot  possibly  produce 
a  paralysis  of  the  respiratory  muscles,  although  it  gives  rise  to  a  uni- 
lateral paralysis  of  the  other  skeletal  muscles. 

It  might  also  be  stated  that  several  authors  have  not  felt  inclined 
to  accept  this  rather  sharp  localization  of  Flourens.  Gierke,  ^  for  ex- 
ample, regards  the  tractus  solitarius  as  an  important  part  of  this  cen- 
ter, wliile  Mislawsky-  holds  a  similar  view  regarding  a  stretch  of  gray 
matter  in  the  vicinity  of  the  hypoglossal  nucleus.  To  be  brief,  it 
seems  that  the  respiratory  center  is  not  confined  to  a  point-like  zone 
of  bulbar  gray  matter,  but  occupies  a  more  extensive  area,  inclusive  of 
its  connections  with  other  bulbar  centers  and  the  nuclei  of  important 
cranial  nerves.  With  Gad,^  it  may  be  assumed  that  really  the  entire 
formatio  reticularis  enters  into  the  formation  of  the  bilaterally  coordi- 
nated center  of  respiration. 

A  very  general  localization  of  this  center  may  be  effected  in  the 
following  way:  A  deeply  anesthetized  animal  is  connected  with  a 
stethographic  arrangement  for  recording  the  respiratory  movements. 
A  section  is  then  made  transversely  through  the  region  of  the  pons. 
Inasmuch  as  the  respiratory  motions  continue  after  this  cut  has  been 
made,  it  is  evident  that  the  center  is  situated  in  the  bulb  or  spinal 
cord.  A  second  cross-section  is  then  made  below  the  lower  root  of  the 
phrenic  nerve,  at  about  the  level  of  the  sixth  cervical  vertebra.  Since 
the  respiratory  movements  do  not  cease  even  now,  it  is  obvious  that 
the  main  center  is  situated  above  the  level  of  the  second  cut,  i.e.,  either 
in  the  medulla  or  upper  cervical  cord.  The  latter  point  may  now  be 
decided  by  piercing  the  lower  region  of  the  bulb,  when  the  respiratory 
motions  will  cease  immediately. 

This  result  may  also  be  obtained  by  dividing  the  spinal  cord  be- 
tween the  main  center  and  the  nuclei  of  the  phrenic  nerves  situated 
opposite  the  fourth  and  fifth  cervical  vertebrae.  In  this  case,  however, 
the  respiratory  standstill  is  not  caused  by  the  destruction  of  the 
center,  but  solely  on  account  of  its  separation  from  its  principal  motor 
apparatus,  consisting  of  the  phrenic  nuclei  and  phrenic  nerves  innervat- 
ing the  diaphragm.     Inasmuch  as  this  muscle  is  absolutely  essential 

1  Archiv  fiir  Anat.  und  Physiol.,  1893,  583. 

2  Zentralbl.  fiir  die  med.  Wissensch.,  1885,  465. 

3  Archiv  fiir  Anat.  und  Physiol.,  1893,  75. 
34 


530  RESPIRATION 

to  respiration,  its  isolation  and  subsequent  paralysis  would  make  life 
practically  impossible.  This  is  especially  true  of  young  animals. 
For  this  reason,  it  has  been  advocated  to  regard  the  various  nuclei  of 
the  nerves  innervating  the  different  muscles  of  respiration,  as  secondary 
or  tributary  centers  to  the  main  or  medullar}^  center  of  respiration. 
It  does,  however,  seem  scarcely  necessary  or  helpful  to  look  at  the 
respiratory  mechanism  in  this  way,  because  in  reality  these  different 
nuclei  form  nothing  more  than  mere  stations  upon  the  efferent  path  and 
do  not  possess  automatic  power.  The  fact  that  the  respiratory^  center 
is  situated  in  the  medulla,  may  also  be  proved  by  injuring  this  sti-ucture 
directly,  as  may  be  done  by  introducing  a  pointed  instrument  between 
the  adjoining  dorsal  borders  of  the  atlas  and  axis.  This  constitutes 
the  act  of  pithing,  a  procedure  which  leads  to  an  almost  instantaneous 
stoppage  of  respiration  and  a  loss  of  the  vascular  tonus  on  account  of 
the  destiTiction  of  the  vasomotor  center.  The  cardiac  center  is  also 
involved,  although  the  heart  itself  continues  to  beat  for  a  brief  period 
of  time.  Very  similar  conditions  may  be  produced  by  sharply  bending 
the  head  upon  the  trunk,  in  which  case  the  odontoid  process  of  the  axis 
may  lacerate  the  bulbar  tissue. 

The  Cause  of  the  Activity  of  the  Respiratory  Center. — The  foregoing 
discussion  has  shown  that  the  respiratoiy  motions  are  incited  at  regu- 
lar intervals  by  impulses  sent  out  by  the  center.  The  question  which 
now  presents  itself  is  this:  Does  this  center  possess  the  power  of 
discharging  these  rhj^hmic  impulses  in  consequence  of  an  inherent 
property  of  its  constituents,  or  does  its  activity  depend  upon  afferent 
impulses  conveyed  to  it  from  other  parts  of  the  body?  In  brief,  there- 
fore, it  would  be  necessary  to  ascertain  whether  the  cells  of  the  respira- 
tory center  possess  an  automatic  power,  such  as  is  exhibited  by  the 
components  of  the  cardiac  center,  or  whether  they  are  activated  solely 
in  a  reflex  way. 

It  must  be  conceded  that  the  former  view  is  the  correct  one,  i.e., 
the  rhythm  is  inherent  in  these  nerve  cells  and  is  not  generated  in  a 
reflex  manner.  This  conclusion  is  based  upon  the  fact  that  the  center 
may  be  completely  isolated  from  the  rest  of  the  body  by  the  division 
of  its  afferent  connections  without  producing  an  absolute  cessation  of 
the  respiratory  movements.  An  experiment  of  this  kind  necessitates 
the  division  of  the  brain  stem  above  the  medulla  and  the  severance  of 
the  vagi  and  glossopharj^ngeal  nerves.  In  addition,  the  spinal  cord 
must  be  cut  across  below  the  nuclei  of  the  phrenic  nerves,^  and  must 
also  be  rendered  impermeable  to  sensory  impulses  by  dividing  the  pos- 
terior roots  in  its  cervical  portion.  But  even  now  the  objection  might 
be  raised  that  the  center  cannot  be  considered  as  being  completely 
isolated  as  long  as  it  remains  in  connection  with  such  efferent  nerves 
as  the  phrenics,  the  probabihty  being  that  these  nerves  also  conduct 
in  a  centripetal  direction.  This  contention  has  been  disproved  in 
the  following  way.  Having  thoroughly  curarized  an  animal  in  order 
1  Loewy,  Pfliiger's  Archiv,  xlii,  1889,  245. 


THE    NERVOUS    REGULATION    OF    RESPIRATION  531 

to  paralyze  its  skeletal  miisciilatTire/  the  phrenic  nerves  were  cut  and 
their  central  ends  connect<Ml  with  a  galvanometer.  It  was  foiinrl  that 
these  nerves  continiunl  to  conduct  action  currents  in  a  ccmtrifiifral 
direction,  clearly  indicating  thereby  a  rhythmic  activity  on  the  part 
of  the  respiratory  center.  The  chemicophysical  causes  underlying;  this 
automatism  are  wholly  unknown,  i.e.,  we  have  almost  no  conception 
regarding  the  manner  in  which  the  metabolic  activity  of  neuroplasm 
can  give  rise  to  a  nervous  action  of  this  kind. 

When  speaking  of  the  respiratoiy  center,  we  frequently  lose  sight 
of  the  fact  that  this  structure  has  to  fulfill  a  double  function,  because 
it  activates  not  only  the  muscles  of  inspiration  but  also  those  of 
expiration.  To  be  sure,  under  normal  conditions  only  the  former  are 
brought  into  play,  while  the  latter  remain  passive,  but  conditions  may 
arise  at  any  time  which  make  it  imperative  to  increase  the  pulmo- 
nary ventilation  by  an  active  participation  of  the  expiratory  muscles. 
It  may  be  assumed,  therefore,  that  the  respiratory  center  consists 
in  reality  of  two  parts,  namely,  of  an  inspiratory  and  an  expiratory. 
It  is  conceivable  that  the  function  of  this  entire  aggregation  of  nerve 
cells  is  distributed  in  such  a  way  that  the  control  of  the  inspiratory 
muscles  is  apportioned  to  some  of  them,  while  others  are  concerned 
exclusively  with  the  expiratory  process.  This  view  may  be  justified 
by  certain  experimental  evidence,  in  spite  of  the  fact  that  the  separate 
existence  of  an  expiratory  center  has  not  been  proven.  At  all  events, 
it  is  evident  that  the  activity  of  these  cells  does  not  conflict  with  the 
function  of  those  controlling  the  inspiratory  mechanism;  in  fact,  it  is 
really  subordinated  to  that  of  the  latter.  Thus,  active  expiratory  ef- 
forts are  invariably  made  when  the  venosity  of  the  blood  is  increased, 
the  purpose  of  these  being  to  aid  the  inspiratory  mechanism  in  remedy- 
ing this  condition.  In  a  volitional  way,  the  expiratory  mechanism  is 
brought  into  play  during  the  acts  of  micturition,  defecation,  parturi- 
tion, coughing  and  sneezing,  and  in  all  these  instances  the  inspiratory 
mechanism  is  made  to  conform  absolutely  to  the  expiratory.  Such  an 
interaction  gives  rise  to  the  so-called  "  abdominal  press,"  which  plays 
an  important  part  in  the  expulsion  of  the  feces  and  urine. 

The  Regulation  of  the  Activity  of  the  Respiratory  Center. — Since 
it  has  been  shown  that  the  power  of  automaticity  is  restricted  to  the 
respiratory  center,  it  should  now  be  evident  that  the  inspiratory 
movements  must  cease  whenever  the  muscles  expanding  the  thorax 
are  separated  from  it.  It  will  be  seen,  therefore,  that  the  respiratory 
mechanism  differs  somewhat  from  that  controlling  the  activity  of  the 
heart,  because  while  the  latter  organ  is  also  regulated  by  an  automatic 
center,  it  possesses  the  power  of  continuing  its  contractions  even  after  it 
has  been  separated  from  the  central  nervous  system.  Thus,  unlike  the 
respiratory  muscles,  the  heart  is  capable  of  developing  an  automaticity 
of  its  own.  Keeping  these  facts  clearly  in  mind,  the  further  statement 
may  now  be  made  that  the  automaticity  of  the  respiratory  center  may 
1  Winterstein,  Pfiuger's^Archiv,  cxxxviii,  1911,  159. 


532  RESPIRATION 

be  varied  at  any  time  by  conditions  arising  elsewhere  in  the  body. 
Moreover,  these  conditions  may  affect  its  activity  in  two  ways,  namely, 
by  means  of  the  gaseous  constituents  of  the  blood  as  it  passes  by  its 
cellular  components  and  secondly,  by  impulses  conducted  to  it  from 
other  parts  of  the  body. 

The  chemical  regulation  of  respiration  has  a  nutritive  basis,  because 
it  is  a  well-known  fact  that  an  increased  venosity  of  the  blood  supplying 
the  center  immediately  leads  to  an  augmentation  of  the  respiratory 
movements.  Conversely,  a  greater  aeration  of  the  blood  gives  rise  to  a 
lessened  respiratory  frequency  and  amplitude.  It  is  readily  possible 
to  change  a  dyspneic  type  of  breathing  into  an  apneic  type,  and 
vice  versa.  In  either  case,  the  question  immediately  arises,  whether 
the  oxygen  or  the  carbon  dioxid  is  the  stimulating  agent.  Thus,  it 
may  readily  be  surmised  that  the  respiratory  movements  may  be 
rendered  dyspneic  either  by  decreasing  the  amount  of  the  oxygen 
(Rosenthal),  or  by  increasing  the  quantity  of  the  carbon  dioxid 
(Traube) .  The  evidence,  recently  collected  by  Haldane  and  his  pupils,  ^ 
seems  to  show  that  neither  one  of  these  factors  can  be  ruled  out  abso- 
lutely. It  is  very  obvious,  however,  that  the  center  is  especially  sen- 
sitive to  changes  in  the  carbon  dioxid  content  of  the  blood ;2  in  fact, 
the  stimulating  potency  of  this  gas  is  so  great  that,  under  normal  con- 
ditions, the  oxygen  cannot  play  an  important  part  in  the  regulation 
of  respiration.  It  is  true,  however,  that  these  two  conditions  gener- 
ally go  hand  in  hand,  because  an  increased  production  of  carbon  dioxid 
necessitates  a  greater  intake  of  oxygen. 

In  illustration  of  this  statement,  it  might  be  mentioned  that  a 
decided  augmentation  of  the  respiratory  movements  can  only  be 
attained  if  the  oxygen  pressure  of  the  alveolar  air  is  reduced  from  its 
normal  value  of  20  per  cent,  to  about  13  per  cent,  of  an  atmosphere. 
In  fact,  in  many  instances  the  subject  of  the  experiment  is  absolutely 
unaware  of  any  scarcity  of  oxygen,  although  the  color  of  his  skin  and 
mucous  surfaces  clearly  betrays  a  marked  deficiency  in  oxyhemoglobin. 
Unconsciousness  frequently  sets  in  before  an  augmentation  in  the 
respiratory  rate  has  been  noticed.  Consequently,  the  action  of  the 
oxygen  upon  the  center  seems  to  consist  merely  in  its  preventing  the 
accumulation  of  the  products  of  metabolism  by  quickly  oxidizing  them. 
Whenever  this  gas  is  present  in  insufficient  amounts,  the  cells  soon 
become  overloaded  with  these  waste  products.  This  condition  in- 
creases their  irritability  so  that  the  carbon  dioxid  finally  acquires  a 
greater  potency  as  a  respiratory  stimulant.^ 

Much  more  decisive  results  are  obtained  with  carbon  dioxid, 
because  an  increase  in  the  tension  of  this  gas  in  the  alveolar  air  of  only 
2  per  cent,  suffices  to  increase  the  pulmonary  ventilation  50  per  cent. 
A  rise  of  3  per  cent,  increases  it  126  per  cent,  and  a  rise  of  6  per  cent. 

1  Jour,  of  Physiol.,  xviii,  1895,  442,  and  xxxii,  1905,  225. 

2  Zuntz,  Pfliiser's  Archiv,  xcv,  1903,  192. 

3  Haldane  and  Poulton,  Jour,  of  Physiol.,  xxx-vii,  1908,  390. 


THE    NERVOUS   REGULATION    OF   RESPIRATION  533 

757  per  cent.  Furthermore,  it  is  a  matter  of  common  experience  that 
the  breath  can  be  held  for  only  a  brief  period  of  time,  obviously  be- 
cause the  tension  of  the  carbon  dioxid  in  the  blood  gradually  attains 
so  great  a  stimulating  power  upon  the  respiratory  center  that  it  can 
no  longer  ])e  subdued  })y  volitional  efforts.  A  longer  respiratory  stand- 
still may  be  effected  either  by  taking  several  deep  breaths  beforehand 
or  by  inhaling  pure  oxygen.  These  procedures  are  intended  to  remove 
much  of  the  superfluous  carbon  dioxid  from  the  lungs  and  to  supply 
them  with  enough  oxygen  to  postpone  the  excitatory  influence  of  the 
waste  products.  It  is  evident,  therefore,  that  the  respiratory  center 
is  under  the  direct  influence  of  the  blood  traversing  it.  As  long  as  the 
carbon  dioxid  tension  of  the  latter  remains  normal,  the  respiratory 
movements  retain  their  eupneic  character,  while  any  increase  in  the 
tension  of  this  gas  is  immediately  followed  by  hyperpneic  and  dyspneic 
breathing.  The  tendency  is  to  adjust  the  depth  and  frequency  of  the 
respiratory  movements  in  such  a  way  that  the  pulmonary  ventilation 
is  always  kept  the  same.  Any  changes  in  the  gas  content  of  the 
blood,  whether  brought  about  by  internal  or  external  causes,  affect 
the  center  directly  and  are  immediately  compensated  for  by  increasing 
or  decreasing  its  automatic  activity. 

The  reflex  regulation  of  respiration  is  made  possible  by  a  multitude 
of  afferent  impulses,  which  take  their  origin  in  different  receptors. 
Thus,  it  is  a  matter  of  common  experience  that  the  amplitude  and 
frequency  of  the  respiratory  motions  may  be  varied  not  only  by  sudden 
changes  in  the  intensity  of  the  light  and  unusual  auditory  impacts, 
but  also  by  sensations  of  smell,  taste,  touch,  pain  and  temperature. 
In  addition,  the  automaticity  of  the  respiratory  center  may  be  altered 
by  impulses  conveyed  to  it  from  the  psychic  centers  of  the  cerebiTim. 
The  latter,  therefore,  must  be  classified  in  large  part  as  volitional  dis- 
charges which  reach  this  center  by  way  of  diverse  transcortical  paths. 
To  this  class  also  belong  the  impulses  arising  in  consequence  of  emo- 
tional conditions. 

A  cold  bath  most  generally  produces  a  deepening  and  acceleration 
of  the  respiratory  movements,  while  the  inhalation  of  irritating  emina- 
tions  leads  to  an  almost  instantaneous  respiratory  standstill.  Very- 
similar  modifications  follow  the  excitation  of  the  receptors  situated  in 
the  realm  of  the  splanchnic  and  sexual  organs,  but  it  would  lead  us 
altogether  too  far  to  discuss  these  reactions  in  detail,  and  besides,  their 
analysis  most  generally  presents  no  serious  difficulty.  A  certain  num- 
ber of  them,  however,  merit  special  consideration,  because  they  origi- 
nate along  the  pulmonary  passage  and  influence  respiration  in  a  most 
decisive  manner.  Reference  is  now  had  particularly  to  the  acts  of 
sneezing  and  coughing,  resulting  in  consequence  of  the  excitation  of 
the  lining  membrane  of  the  nasal,  pharyngeal  and  laiyngeal  cavities. 
In  accordance  with  the  innervation  of  these  parts,  it  may  be  surmised 
that  these  reflexes  are  effected  principally  with  the  help  of  the  vagi 
nerves,  which  contain  afferent  as  well  as  efferent  respiratory  fibers. 


534  RESPIRATION 

Keeping  these  facts  clearly  in  mind,  it  is  now  possible  to  assign  a 
definite  cause  to  the  taking  of  the  first  breath.  In  utero,  the  respira- 
tory center  of  the  fetus  is  not  subjected  to  a  stimulation  by  the  carbon 
dioxid,  because  its  blood  and  tissues  are  constantly  kept  in  an  apneic 
condition.  Subsequent  to  the  obliteration  of  the  umbilical  blood- 
vessels, however,  the  carbon  dioxid  accumulates  very  rapidly  and 
finally  incites  the  center  to  send  out  those  impulses  which  give  rise  to 
the  first  respiratory  movement.  This  process  is  materially  hastened 
by  mechanical  and  thermal  stimuli,  because  the  conditions  which  the 
fetus  meets  with  during  and  directly  after  the  period  of  labor  are 
very  different  from  those  to  which  it  has  been  subjected  in  utero.  It 
exchanges  a  practically  indifferent  medium  heated  to  the  temperature 
of  the  body,  with  one  much  cooler  and  teeming  with  mechanical  im- 
pacts of  all  sorts. 

The  Innervation  of  the  Upper  Respiratory  Passage. — With  the 
exception  of  a  small  patch  of  modified  epithelium  forming  the  so-called 
olfactory  area,  all  sensory  impressions  from  the  mucous  membrane  of 
the  nose  are  relegated  to  the  system  of  the  trigeminal  nerve.  In 
accordance  with  the  character  of  the  stimulus,  these  afferent  impulses 
give  rise  either  to  an  acceleration  or  a  retardation  of  the  respiratory 
movements.  In  the  latter  case,  respiration  may  be  arrested  with  the 
chest  in  either  the  inspiratory  or  expiratory  position.  It  need  scarcely 
be  mentioned  that  the  impulses  generated  in  the  nasal  cavity,  are  first 
relayed  to  the  respiratory  center  by  way  of  the  trigeminus  and  are 
then  conveyed  to  the  different  muscles  of  respiration.  These  stimuli 
are  usually  followed  by  an  active  expiration,  the  blast  of  air  being  ex- 
pelled through  the  nasal  cavity,  while  the  oral  cavity  is  temporarily 
shut  off  by  the  closure  of  the  fauces.  This  constitutes  the  act  of 
sneezing,  the  purpose  of  which  is  to  dislodge  the  irritating  body  from 
the  nose. 

A  similar  reflex  mechanism  for  safeguarding  the  respiratory  passage 
is  situated  in  the  pharynx.  The  lining  of  this  cavity  is  innervated 
in  a  sensory  way  by  the  glossopharyngeal  nerves.  Moderate  excita- 
tions occurring  in  the  realm  of  these  nerves  are  immediately  followed 
by  an  inhibition  of  respiration  and  an  active  expiration,  but  in  this 
case  the  posterior  nares  are  closed  and  the  expiratory  blast  of  air  is 
expelled  through  the  oral  cavity.  This  constitutes  the  act  of  coughing. 
These  impulses  from  the  terminals  of  the  glossopharyngeus  are  of 
special  value  during  the  act  of  swallowing,  because  they  lead  to  a 
temporary  arrest  of  the  inspiratory  movement  and  a  closure  of  the 
epiglottis  so  that  the  food  cannot  be  aspirated  into  the  laryngeal  cavity. 
The  path  pursued  by  these  impulses  is  the  same  as  that  outlined  pre- 
viously, i.e.,  they  are  first  relayed  to  the  nucleus  of  this  nerve  and  to 
the  respiratory  center,  whence  they  are  directed  to  the  muscles  of 
respiration. 

On  passing  into  the  cavity  of  the  larynx  another  nerve  is  met  with, 
namely,  the  superior  laryngeal  branch  of  the  vagus  (Fig.  263).     It  is  a 


THE    NERVOUS    REGULATION    OF    RESPIRATION 


535 


matter  of  common  experionco  tluit  the  entrance  of  a  foreign  body  into 
the  larynx  causes  an  immediate  inhibition  of  inspiration  and  a  forced 
expiration,  the  air  beinjij  ejected  in  this  case  through  the  mouth.  It 
need  scarcely  ]>e  repeated  that  the  impulses  generated  in  this  region 
of  the  respiratory  passage,  are  first  conducted  through  the  nuclei  of 
the  vagi  nerves  to  the  respiratory  center, 
whence  the  efferent  discharges  are  di- 
verted to  the  different  muscles  of  respira- 
tion. Obviously,  the  division  of  either 
the  right  or  left  superior  laryngeal  nerve 
must  render  the  corresponding  side 
of  the  larynx  insensitive  to  stimulation. 
Furthermore,  inasmuch  as  this  nerve  is 
the  only  sensory  nerve  of  this  organ,  the 
division  of  both  nerves  must  lead  to  a 
complete  paralysis  of  sensation.  An 
animal  cannot  long  survive  this  proced- 
ure, because  the  gradual  accumulation 
of  foreign  substances  in  the  upper  res- 
piratory passage  finally  involves  the  lung 
tissue  and  gives  rise  to  an  inflammatory 
reaction  which  bears  the  essential  char- 
acteristics of  pneumonia. 

While  discussing  this  subject,  it  might 
be  well  to  mention  that  the  superior 
laryngeal  nerves  are  not  entirely  sensory 
in  their  function,  but  also  embrace  a 
number  of  efferent  fibers  which  innervate 
the  cricothyroid  muscles  (Fig.  263). 
Keeping  these  facts  clearly  in  mind,  it 
will,  therefore,  be  seen  that  the  stimula- 
tion of  the  intact  superior  laryngeal  nerve 
must  produce  impulses  which  (a)  pursue 
an  afferent  course  and  give  rise  to  an  in- 
hibition of  inspiration  and  a  forced  ex- 
piration, and  (6)  pass  in  an  efferent  direc- 
tion to  cause  a  contraction  of  the  corre- 
sponding cricothyroid  muscle.  Accord- 
ingly, the  division  of  this  nerve  must  in- 
duce a  loss  of  sensation  on  the  side  of 

the  injury,  as  well  as  a  paralysis  of  the  corresponding  cricothyroid 
muscle.  The  stimulation  of  the  distal  end  of  the  divided  nerve  then 
gives  a  contraction  of  the  cricothyroid  muscle,  while  the  excitation 
of  its  central  end  elicits  those  sensations  which  ordinarily  produce  an 
inspiratory  standstill  and  forced  expiratory  blasts  of  air. 

The  larynx  also  receives  a  second  nerve  supply  by  way  of  the 
inferior  laryngeal  branches  of  the  vagus  (Fig.  263).     Since  these  nerves 


Fig.  263. — The  Innervation 
OF  THE  Larynx  (Posterior  View; 
One  Side). 

B,  base  of  tongue;  E,  epi- 
glottis; ^4,  arytenoid  muscles; 
CA,  crico-arytenoid  muscle;  T, 
trachea;  F,  vagus  nerve;  SL, 
superior  laryngeal  nerve;  J  and 
O,  its  inner  and  outer  branches; 
JL,  inferior  laryngeal  nerve;  Bt, 
vagal  fibers  innervating  bron- 
chial musculature. 


536  RESPIRATIOX 

are  given  off  in  the  thorax  and  then  return  along  the  trachea  to  enter 
the  inferior  aspect  of  this  organ,  they  are  generally  designated  as  the 
"recurrent"  nerves.  They  are  wholly  motor  in  their  function  and 
innervate  all  the  larj-ngeal  muscles  with  the  exception  of  the  crico- 
thjToids.  OVjviously,  therefore,  the  excitation  of  this  nerve  on 
either  the  right  or  left  side,  must  cause  a  contraction  of  the  muscles  in 
the  corresponding  half  of  the  larynx,  with  the  exception  of  the  one 
just  mentioned.  Accordingly,  the  division  of  one  or  the  other  of  these 
nerves  must  lead  to  a  unilateral  motor  paralysis  of  thxis  organ,  and  the 
division  of  both  nerves,  to  a  bilateral  paralysis.  Inasmuch  as  these 
nerves  conduct  only  in  the  direction  from  the  center  to  the  larynx 
and  are,  therefore,  efferent  in  their  fimction,  the  excitation  of  their 
distal  ends  must  give  rise  to  a  contraction  of  all  the  larv-ngeal  muscles, 
with  the  exception  of  the  cricothjToids.  For  the  same  reason,  the 
stimulation  of  their  central  ends  cannot  influence  the  respiratory 
rate  or  amplitude. 

The  Function  of  the  Vagus  Nerve. — The  preceding  discussion 
f>ertaining  to  the  superior  and  inferior  larvTigeal  branches  of  the  vagus, 
must  lead  us  to  suspect  that  the  cen,'ical  portion  of  the  main  trunk  of 
this  nerve  embraces  afferent  as  well  as  efferent  respiratory  fibers. 


Fig.  264. — Stethogeafhic   Recoed  of   the    Resptratoey    Movements    (Dog;    Afteb 
Division  of  the  Left  (LV)  axd  Right  (RV)  Vagi  Xer^-es. 

This  as.sumption  may  be  tested  experimentally  by  simply  flividing 
one  or  both  nerves  above  or  below  the  points  of  origin  of  their  superior 
larj'ngeal  Vjranches.  In  either  ca.se,  this  procedure  is  followed  almost 
immediately  by  a  reduction  in  the  frequency  and  an  increase  in  the 
depth  of  the  respiratory  movements.  The  individual  movements 
become  pronouncedly  inspiratory  in  their  character,  and  more  so, 
if  both  nerves  have  been  divided.  This  change,  however,  does  not 
necessarily  give  ri.se  to  a  dyspneic  condition  of  the  animal,  because 
the  amount  of  air  fumi.shed  by  these  slow  and  deep  respirations, 
is  practically  the  same  as  that  previously  supplied  by  the  more  fre- 
quent and  shallow  movements.  It  is  true,  however,  that  the  division 
of  both  vagi  nerves  renders  the  animal  incapable  of  adjusting  itself 
to  different  conditions.  Thus,  if  it  is  made  to  inhale  air  containing 
a  large  percentage  of  carbon  dioxid,  it  fails  to  compensate,  owing  to 
its  inabiUty  to  increa.se  its  respiratory  frequency.  Working,  therefore, 
on  so  small  a  margin,  its  pulmonarj^  ventilation  soon  h)ecomes  in- 
adequate for  the  relief  of  the  high  carVjon  dioxid  teasion  of  the  blood. 


THE    NERVOUS    REGULATION    OF    RESPIRATION  537 

In  fiddition,  the  procedure  of  double  vagotomy,  as  the  cHvision  of 
both  vagi  nerves  is  called,  invariably  leads  to  other  conditions  which 
are  absolutely  incompatible  with  normal  function. 

Dogs  are  somewhat  more  resistant  and  frequently  survive  this 
operation  for  many  days,  and  in  some  instances  even  for  an  indefinite 
period  of  time,  whereas  rabbits,  sheep  and  horses  succumb  to  it  in  the 
course  of  a  few  days.  In  addition  to  the  effects  upon  respiration 
and  the  action  of  the  heart,  these  animals  also  exhibit  difficulties 
in  deglutition,  digestion  and  assimilation.  They  lose  weight  constantly 
until  their  lungs  eventually  consolidate  in  consequence  of  a  pneumonic 
affection.  Whether  this  infiltration  of  the  pulmonary  tissue  is  caused 
by  trophic  influences  or  by  the  ingress  of  food  and  bacteria,  owing 
to  the  functional  uselessness  of  the  epiglottis,  has  not  been  definitely 
ascertained. 

The  division  of  these  nerves  should  really  be  effected  by  the  method 
of  freezing  rather  than  by  that  of  cutting,  because  by  this  means  their 
power  of  conduction  may  be  destroyed  without  the  usual  initial 
period  of  excitation.^  This  accounts  for  the  fact  that  the  diminution 
in  the  respiratory  activity  is  commonl}-  initiated  by  a  hyperpneic  type 
of  respiration.  Furthermore,  it  should  be  remembered  that  these 
alterations  in  the  frequency  and  depth  of  the  respiratory  movements 
manifest  themselves  only  if  both  nerves  are  cut  and  that  the  division 
of  only  one  nerve  generally  produces  little  or  no  change.  Aside  from 
the  motor  effects  evoked  with  the  aid  of  the  inferior  laryngeal  nerve, 
the  stimulation  of  the  distal  end  of  the  divided  vagus  leaves  the  general 
character  of  the  respiratory  movements  unchanged.  It  should  be 
noted,  however,  that  this  nerve  also  contains  efferent  fibers  for  the 
musculature  of  the  bronchi  (Fig.  263).  This  has  been  shown  by  Roy 
and  Brown,-  as  well  as  by  Einthoven,'  who  have  found  that  the  excita- 
tion of  either  vagus  produces  a  constriction  of  the  bronchi  of  both 
lungs,  while  the  division  of  either  nerve  eventually  evokes  a  dilatation 
of  these  tubes  on  the  side  of  the  section.  It  may  readity  be  surmised 
that  these  changes  in  the  size  of  the  bronchial  passage  must  lead  to 
variations  in  the  volume  of  the  air  contained  therein.  In  this  con- 
nection it  should  also  be  mentioned  that  the  recurrent  attacks  of 
dyspnea,  characterizing  spasmodic  asthma,  are  believed  to  be  as- 
sociated with  spasms  of  the  bronchial  musculature.  These  are  said 
to  find  their  origin  in  a  neuritic  condition  of  the  vagus  nerve. 

The  excitation  of  the  central  end  of  the  divided  vagus  nerve  with 
a  quickly  interrupted  current  may  be  followed  by  either  a  slowing  or  a 
quickening  of  the  respiratory  movements.  The  precise  character  of  the 
effect  produced  by  this  procedure  depends  upon  the  strength  of  the 
stimulus   and   the   irritability   of   the   respiratory   mechanism.^     To 

1  Gad,  Archlv  fiir  Anat.  und  Physiol.,  1880,  9. 

2  Jour,  of  Physiol.,  vi,  1885,  21. 

3  Pfliiger's  Archiv,  ci,  1892,  367. 

*  Rosenthal,  Archiv  fiir  Anat.  und  Ph3'siol.,  1881,  39. 


538  RESPIRATION 

begin  with,  however,  it  maj-  be  well  to  state  that  currents  of  moderate 
strength  invariably  evoke  a  respiratory  standstill  in  the  inspiratory 
position.  This  phenomenon  is  practically  identical  with  that  observed 
upon  stimulation  of  the  intact  superior  laiyngeal  nerv^e,  or  of  its 
central  end.  Very  weak  stimuli  are  prone  to  develop  expiratory 
tendencies  which  are  usually  accompanied  by  an  inhibition  of  the 
inspiratory  movements.  With  strong  currents  the  results  are  per- 
plexing, although  it  is  quite  e^'ident  that  they  consist  essentially 
in  a  respiratory  cessation  with  the  chest  either  in  the  inspiratory 
or  expirator^^  position.  It  need  scarcely  be  mentioned  that  these 
effects  may  also  be  evoked  by  the  stimulation  of  the  intact  vagus. 

The  Self -regulation  of  Respiration. — The  foregoing  experimental 
data  show  very  clearly  that  the  division  of  the  vagi  nerves  prevents 
certain  stimuli  from  reaching  the  respiraton,'  center  which  originate 
along  the  pulmonary-  passage  and  ordinarily  tend  to  increase  the  activity 
of  these  ganglion  cells.  When  no  longer  under  the  influence  of  these 
afferent  impulses,  the  center  falls  back  upon  its  inherent  automaticity, 
which  gives  rise  to  regular  but  relatively  infrequent  impulses.  In 
the  second  place,  it  must  be  concluded  that  the  vagus  nerve  em- 
braces two  kinds  of  afferent  fibers,  or  rather,  afferent  fibers  which  are 
capable  of  conducting  two  types  of  impulses.  One  of  these  inhibits 
inspiration  and  the  other  expiration.  Accordingly,  it  may  be  con- 
jectured that  the  inliibition  of  the  inspirator^''  muscles  allows  the 
development  of  the  expiratoiy  process,  while  the  inhibition  of  the 
expiratory  muscles  favors  the  occurrence  of  inspiration. 

In  accordance  with  this  exposition  Hering  and  Brener^  have 
formulated  the  hypothesis  that  the  respiratoiy  movements  regulate 
themselves;  i.e.,  every  expiration  incites  an  inspiration  and  every 
inspiration  an  expiration.  The  vagi,  therefore,  are  regarded  as  fonn- 
ing  the  most  important  link  in  a  check-system  which  insures  a  proper 
sequence  and  depth  of  the  successive  respirator}-  movements.  This 
leads  to  a  much  greater  frequency  of  the  respirators'  movements  than, 
could  be  obtained  if  the  center  alone  were  the  controlling  agent.  The 
latter,  as  has  been  shown  above,  possesses  a  slow  rate  of  discharge. 
When  the  lungs  are  expanded,  a  stimulus  is  set  up  in  these  organs 
which  travels  over  the  inspiratoiy  fibers  of  the  vagus  and  eventually 
stops  this  movement,  permitting  expiration  to  set  in.  Quite  similarly, 
the  deflation  of  the  lungs  reflexly  incites  the  subsequent  inspiration. 
Whether  these  intrapulmonic  stimuli  are  chemical  or  mechanical 
in  their  nature  is  a  much  debated  question.  It  seems,  however,  that 
the  mechanical  ones  are  the  most  important.  They  find  their  origin 
in  the  alternate  stretching  of  the  vagal  terminals  which  may  be 
imagined  to  invest  the  bronchial  tubes  in  the  manner  of  caUpers. 
It  should  be  remembered,  however,  that  the  expiratory"  process  is  a 
passive  phenomenon  and  is  not  associated  under  ordinarj'  conditions 
with  a  contraction  of  the  respiratory  muscles,  and  hence,  the  inhibiting 

1  Sitzungsb.  der  Wiener  Akad.  der  Wissensch.,  cviii,  1868,  909. 


THE    NERVOUS    REGULATION    OF   RESPIRATION 


539 


suddenly 
is    called 


artif  resp  app. 


fibers  of  inspiration  would  not  be  brought  into  play  during  quiet 
respiration.  An  activation  of  the  latter,  however,  would  result 
whenever  forced  expirations  are  required  to  effect  a  more  thorougii 
alveolar  ventilation.  This  mechanism,  therefore,  insures  the  perfect 
regulation  of  the  central  discharges  so  that  they  develop  at  perfectly 
precise  intervals,  but  naturally,  it  is  not  concerned  with  the  produc- 
tion of  the  automaticity  of  the  center. 

This  hypothesis  may  be  tested  in  a  simple  way  by 
inflating  or  deflating  the  lungs.  The  first  procedure 
positive  ventilation  and  is  invari- 
ably followed  by  a  relaxation  of  the 
diaphragm  and  a  long  expiratory 
pause,  whereas  the  second,  or  nega- 
tive ventilation,  induces  a  contrac- 
tion of  this  septum.  Besides,  the 
existence  of  inspiratory  and  expira- 
tory fibers  in  the  vagus  is  also  made 
probable  by  the  effects  obtained  on 
stimulation  of  the  intact  vagus  or 
of  its  central  end;  in  fact,  Griitzner^ 
and  Langendorf-  have  proved  that 
the  application  of  a  constant  current 
to  the  vagus  results  in  an  inspiratory 
arrest  when  descending,  and  in  an 
expiratory  standstill  when  ascending. 
In  addition,  it  might  be  stated  that 
the  collapse  of  the  lungs  invariably 
gives  rise  to  a  nerve  impulse  which 
ascends  the  vagus  and  may  be  regis- 
tered by  means  of  the  string  galvano- 
meter. Head,^  moreover,  has  ascer- 
tained that  the  collapse  of  either  lung  produces  much  more  decided 
inspiratory  efforts  than  the  division  of  both  vagi  nerves.  This  he 
succeeded  in  showing  in  the  following  way :  The  left  vagus  of  a  rabbit 
having  been  cut,  the  corresponding  lung  was  inflated  rhythmically 
by  means  of  a  tube  inserted  in  the  left  bronchus  (Fig.  265).  The 
normal  action  of  the  right  lung  was  then  suddenly  interrupted  by 
opening  the  right  pleura.  The  resulting  collapse  of  this  organ  incited 
an  immediate  tonic  contraction  of  the  diaphragm  which  generally 
lasted  for  some  time,  although  the  rhythmic  inflation  of  the  left  organ 
prevented  the  occurrence  of  dyspnea  and  asphyxia. 

1  Pfliiger's  Archiv,  cvii,  1894,  98. 

2  Ibid.,  cix,  1906,  201. 

3  Jour,  of  Physiol.,  x,  1889,  1. 


Fig.  265. — Dl'VGRam  to  Illustrate 
Head's  Experiment  on  the  Effect  of 
Collapse  of  the  Lung. 
R.c,  respiratory  center;  r.v,  l.v,  right 
and  left  vagi.      (Starling.) 


SECTION  XIII 
VOICE  AND  SPEECH 


CHAPTER  XLIII 


THE  GENERAL  ARRANGEMENT  OF  THE  PHONATING 

ORGANS 

The  Larynx. — The  production  of  noises  and  sounds  by  animals  may 

be  accidental  and  intentional.  Thus,  the  wings  of  an  insect  beating 
the  air  at  the  rate  of  about  300  times  in  a  second,  produce  a  noise  which 
is  merely  a  phenomenon  accompanying  muscular  action,  but  animals 
of  this  kind  are  also  in  possession  of  certain  mechanisms  by  means 
of  which  a  simple  communication  between  them  is  made  possible. 
The  latter  end  they  attain  by  the  rubbing  together  of  their  hind- 
legs  or  by  the  approximation  of  their  mandibles.  In  amphibians, 
the  trachea  opens  anteriorly  into  the  small  laryngeal  chamber  which 
is  connected  vAih.  the  cavit}^  of  the  mouth  b}'  a  slit-like  opening  or 
glottis.  At  one  point,  the  mucous  membrane  lining  this  chamber,  is 
folded  into  two  transverse  bands,  the  vocal  cords,  which  are  made  to 
vibrate  by  the  expiratory  blasts  of  air.  In  reptiles,  the  trachea  is  more 
distinctly  outlined  and  is  expanded  anteriorly  to  form  the  larynx  with 
its  cartilaginous  walls  and  transverse  vibrating  cords. 

Curiously  enough,  the  phonating  mechanism  of  the  higher  animals 
differs  only  slightly  from  that  found  in  these  forms.  Its  general 
structural  principle,  as  well  as  that  of  several  of  its  minor  parts,  remains 
the  same.  Contrary  to  this  anatomical  uniformitj^,  the  sounds  of 
these  animals  gradually  attain  a  greater  complexitj-  until  they  acquire 
the  character  of  articulated  sounds.  Thus,  vowels  and  consonants 
may  be  distinguished  in  the  notes  of  birds,  which  animals  have  in 
general  a  much  more  extensive  register  than  the  mammals.  Even- 
tually, the  sounds  are  joined  into  words  and  coordinated  to  give  rise 
to  speech.  In  this  regard,  man  is  sharply  differentiated  from  other 
forms,  because  practically  no  other  animal  is  capable  of  equaling 
his  register  of  sounds  nor  his  faculty  of  sound  coordination.  This 
difference,  however,  is  not  brought  about  bj^  a  relatively  much  greater 
structural  perfection  of  his  motor  apparatus,  but  rather  by  a  more 
exclusive  development  of  the  association  area  governing  this  faculty. 
In  the  lower  forms  the  production  of  sounds  is  largely  a  reflex  phe- 
nomenon. It  becomes  a  complex  coordinated  act  only  in  those  species 
which  are  in  possession  not  only  of  association  centers  but  also  of  a  par- 
ticular center,  having  to  do  solely  with  the  control  of  the  production 
of  sounds.     At  the  present  time,  however,  we  are  chiefly   concerned 

540 


GENERAL  ARRANGEMENT  OF  THE  PHONATING  ORGANS   541 


with  the  motor  organ,  namely,  with  the  larynx  and  its  adjuncts  as  well 
as  with  the  nervous  paths  which  connect  this  organ  with  the  motor 
area  in  the  Ilolandic  area  of  the  corel)ral  cortex.  The  function  of  the 
psychic  center  for  speech  and  the  manner  in  which  afferent  impulses 
are  enabled  to  influence  its  action,  will  be  discussed  later  on  in  connec- 
tion with  the  function  of  the  corohrum  and  allied  parts. 

General    Structure    of    the    Larynx. — This    organ    consists    of    a 
framework  of  cartilages  held   together  by  ligaments  and  acted  upon 


Fig. 


Fig.  266.  Fig.  267. 

266. — Lakyngeal  Cartilages  aijd  Ligaments,  Anterior  Surface. 


1,  hyoid  bone;  2,  2,  3,  3,  greater  and  lesser  cornua;  4,  thyroid  cartilage;  5,  thyrohyoid 
membrane;  6,  thyrohyoid  ligaments;  7,  cartilaginous  nodule;  8,  cricoid  cartilage;  9, 
the  cricothyroid  membrane;   10,   the  cricothyroid  ligaments.   11,  trachea.      (Sappey.) 

Fig.  267. — Lar^'ngeal  Cartilages  and  Ligaments,  Posterior  Surface. 

1,  1,  thyroid  cartilage;  2,  cricoid  cartilage;  3,  3,  arytenoid  cartilages;  3,  4,  crico- 
arytenoid articulations;  5,  5,  cricothyroid  articulations;  6,  union  of  the  cricoid  cartilage 
and  of  the  trachea;  7,  epiglottis;  8,  ligament  uniting  it  to  the  reentering  angle  of  the 
thyroid   cartilage.     (Sappey.) 

by  a  system  of  extrinsic  and  intrinsic  muscles.  The  following  carti- 
lages enter  into  its  formation: 

Single  cartilages  Paired  cartilages 
Thyroid  Arytenoid 

Cricoid  Cornicula   laryngis 

Epiglottis  Cuneiform 

But  even  in  the  case  of  the  single  cartilages,  a  certain  tendency  toward 
bilaterahsm  is  unmistakable,  because  they  are  thickest  and  most 
extensive  at  the  sides  of  the  larynx  and  are  united  in  front  by  merely 
a  narrow  bridge  of  connecting  tissue.  These  cartilages  are  adjusted 
upon  the  anterior  extremity  of  the  trachea  in  such  a  way  that  a  rela- 
tively large  cavity  is  formed  which  is  protected  against  the  pharynx 
by  the  epiglottis.  •  Its  pharyngeal  aperture  is  triangular  in  shape, 
its  base  being  directed  forward  and  its  apex  backward. 


542 


VOICE    AND    SPEECH 


The  larynx  as  a  whole,  as  well  as  the  trachea,  is  movable,  because 
it  is  suspended  from  the  hyoid  bone  by  the  thyrohyoid  muscles.  This 
bone  in  turn  is  affixed  to  the  base  of  the  skuU  and  the  maxillse 
by  a  number  of  muscles,  and  is  therefore  also  freely  movable.  The 
upward  movement  of  the  larynx  is  counteracted  by  the  sternothy- 
rohyoid   muscles   which   unite   this   organ   with   the   sternum.     The 

larynx  may  be  displaced  for  a  dis- 
tance of  several  centimeters,  first 
in  consequence  of  the  muscular 
activity  coincident  wdth  the  act  of 
swallowing  and  secondly,  in  con- 
sequence of  the  adjus,tment  of  the 
laryngeal  parts  for  purposes  of 
phonation.  In  the  former  case,  the 
larynx  is  also  tilted  forward,  in- 
suring a  greater  prominence  of  its 
anterior  border. 

In  longitudinal  section  the 
laryngeal  cavity  exhibits  the  shape 
of  an  hour-glass,  the  true  vocal 
cords  forming  the  line  of  demarca- 
tion between  its  upper  and  lower 
recesses.  Moreover,  while  the  long 
axis  of  its  upper  recess  is  directed 
strongly  backward,  that  of  the  lower 
conforms  more  closely  to  the  general 
course  of  the  trachea.  The  thyroid 
cartilage  forms  the  front  and  sides 
of  the  upper  part  of  the  larynx. 
It  is  composed  of  two  nearly  square 
plates  which  are  placed  vertically 
and  are  united  in  front  by  a  bridge 
which  gives  rise  to  a  prominence, 
known  as  the  pomum  Adami. 
Posteriorly,  they  are  rather  widely 
separated  from  one  another,  the  in- 
tervening space  being  filled  by  soft 
tissues.  The  cricoid  cartilage  forms 
a  heavy  ring  which  completely  sur- 
rounds the  lower  cavity  of  the 
larynx.  It  is  narrow  in  front,  but 
broadens  out  posteriorly  into  a  quadrate  plate.  The  latter  is  narrowed 
above  into  a  pointed  process.  The  arytenoid  cartilages  are  two  ir- 
regular, triangular  plates,  the  bases  of  which  are  placed  transversely 
upon  the  superior  processes  of  the  cricoid.  The  corniculce  laryngis  are 
two  small  cone-shaped  cartilages  which  are  fastened  to  the  upper  pro- 


FiG.  268. — Vertical  Transvehse 
Section  of  the  Laeynx.     (After  Tesiut.) 

1,  posterior  face  of  epiglottis,  with  1', 
its  cushion;  2,  aryteno-epiglottic  fold;  3, 
ventricular  band,  or  false  vocal  cord;  4, 
true  vocal  cord;  5,  central  fossa  of 
Merkel;  6,  ventricle  of  larynx,  with  6', 
its  ascending  pouch;  7,  anterior  portion 
of  cricoid;  8,  section  of  cricoid;  9,  thy- 
roid, cut  surface;  10,  thyrohyoid  mem- 
brane; 11,  thyrohyoid  muscle;  12, 
aryteno-epiglottic  muscle;  13,  thyro- 
arytenoid muscle,  with  13',  its  inner 
division,  contained  in  the  vocal  cord;  14, 
cricothyroid  muscle;  15,  subglottic  por- 
tion of  larynx;  16,  cavity  of  the  trachea. 
(American  Text-book  of  Physiology.) 


GENERAL  ARRANGEMENT  OF  THK  PHONATING  ORGANS   543 

jection  of  the  arytenoids.  The  cuneiform  cartilages  are  placed  within 
the  aryteno-epiglottidean  folds. 

The  Function  of  the  Epiglottis. — The  larynx  is  protected  against 
the  digestive  tract  b}-  a  leaf-like  plate  of  yellow  elastic  cartilage  which 
is  attached  below  by  a  stalk  to  the  thyroid  cartilage.  In  the  adult 
it  usually  assumes  a  nearly  vertical  position,  while  in  children  it  is 
placed  more  slantingly.  It  has  a  double  purpose,  namely,  to  prevent 
the  ingress  of  food  into  the  respiratory  passage  and  to  aid  in  the  modi- 
fication of  the  currents  of  air  during  respiration  and  phonation. 

The  closure  of  the  pharyngolaryngeal  opening,  however,  is  not 
effected  solely  by  the  epiglottis,  because  a  rather  efficient  occlusion 
of  this  orifice  is  also  had  when  this  structure  is  wanting  or  is  imper- 
fectly developed.  Neither  is  it  correct  to  assume  that  those  muscle 
fibers  which  arise  upon  the  thyroid  and  are  inserted  upon  the  epiglottis 
are  sufficiently  powerful  to  sei've  as  sphincters.^  A  third  factor  must 
be  taken  into  consideration,  and  that  is  the  elevation  and  forward  in- 
clination of  the  entire  larynx.  This  movement  gives  rise  to  an  approxi- 
mation with  the  hyoid  bone  so  that  the  tongue,  when  drawn  back  dur- 
ing the  act  of  swallowing,  is  in  the  best  possible  position  to  press  the 
epiglottis  downward  until  it  comes  to  lie  across  the  laryngeal  aperture. 
At  this  very  moment,  the  thyro-epiglottidean  muscle  fibers  contract, 
thereby  tending  to  constrict  this  orifice.  It  is  also  held  that  the 
epiglottis  serves  as  a  sort  of  sounding  board  against  which  the  vibrat- 
ing particles  of  air  are  forced.  Thirdly,  its  partial  closure  upon  the 
forced  expiratory  blasts  gives  rise  to  the  peculiar  fragmented  character 
of  the  current  of  the  air  produced  during  the  act  of  coughing.  When 
acting  upon  the  inspiratory  current  of  air,  its  partial  closure  gives  rise 
to  such  peculiar  modifications  as  are  noted  during  the  act  of  hic- 
coughing. The  fact  that  the  mucous  lining  of  this  structure  is  beset 
with  numerous  taste-buds  and  glands  does  not  possess  a  special 
functional  significance. 

The  True  and  False  Vocal  Cords. — When  looked  at  from  above,  the 
wide  expanse  of  the  laryngeal  cavity  is  seen  to  be  limited  by  two 
membranous  bands,  the  vocal  cords,  which  extend  transversely  across 
its  lumen  in  a  direction  from  before  backward.  The  space  between 
these  bands  is  known  as  the  glottis.  The  size  and  shape  of  the  latter 
vary  with  the  respiratory  movements  and  phonation.  During  in- 
spiration it  becomes  large  and  during  expiration  small.  When  the  vocal 
cords  are  widely  separated,  its  width  measures  about  13.5  mm.  in 
men  and  11.5  mm.  in  women.  During  phonation  it  usually  assumes 
the  shape  of  a  mere  slit,  designated  as  the  chink  of  the  glottis,  or  rima 
glottidis. 

The  true  vocal  cords  arise  in  front  from  the  angle  formed  by  the 
alae  of  the  thryoid  cartilages,  and,  passing  directly  backward,  are  in- 
serted upon  the  vocal  processes  of  the  arytenoid  cartilages.     They 

1  Meltzer,  The  Closure  of  Glottis  During  Deglutition,  Zentralbl.  fiir  Physiol., 
xxvi,  1912. 


544 


VOICE    AND    SPEECH 


vary  in  length  in  men  from  15-20  mm.  (average  18.22  mm.)  and  in 
women  from  10-15  mm.  (average  12.6  mm.).  Their  free  edges  are 
thin  and  tilted  slightly  upward,  while  their  outer  margins  are  straight 
and  are  everywhere  adherent  to  the  wall  of  the  larynx.  The  yellow 
elastic  fibers  composing  their  substance,  are  closely  interwoven  and 
pursue  in  general  a  longitudinal  course.  Of  functional  importance  is 
also  the  fact  that  these  bands  are  covered  with  thin,  flat,  stratified 
epithelium,  while  the  remaining  extent  of  the  larynx  is  lined  with  colum- 
nar, ciliated  epithelium.  The  effective  stroke  of  these  cilia  is  executed 
toward  the  pharynx,  i.e.,  in  the  same  direction  as  that  of  the  cilia 
found  in  the  trachea  and  bronchi. 

The  space  above  the  vocal  cords  is  known  as  the  supraglottic 
cavity.     It  is  bounded  above  by  the  epiglottis.     On  each  side  of  the 


17 
Fig.  269. — The  Laryngoscopic  Image  in  Easy  Breathing.  (Sioerk.) 
1,  Base  of  the  tongue;  2,  median  glosso-epiglottic  ligament;  3,  vallecula;  4,  lateral 
glosso-epiglottic  ligament;  5,  epiglottis;  6,  cushion  of  epiglottis;  7,  cornu  major  of  hyoid 
bone;  8,  ventricular  band,  or  false  vocal  cord;  9,  true  vocal  cord;  opening  of  the  ventricle 
of  Morgagni  seen  between  8  and  9;  10,  folds  of  mucous  membrane;  11,  sinus  pyriformis; 
12,  cartilage  of  Wrisberg;  13,  aryteno-epiglottic  fold;  14,  rima  glottidis;  15,  arytenoid 
cartilage;  16,  cartilage  of  Santorini;  17,  posterior  wall  of  pharynx.  (American  Text- 
book of  Physiology.) 

latter  a  fold  of  mucous  membrane  extends  obliquely  downward  and 
backward,  forming  the  lateral  boundary  of  the  aperture  of  the  larynx, 
and  covering  the  arytenoid  cartilages.  Besides  these  ary epiglottic 
folds,  the  mucosa  of  the  larynx  also  presents  two  transverse  ridges, 
one  on  each  side,  which  are  known  as  the  false  vocal  cords.  These 
relatively  narrow  bands  are  situated  a  short  distance  above  the  true 
vocal  cords  and  are  placed  practically  parallel  to  these,  so  that  a  long 
slit-like  space  is  left  between  them.  The  function  of  these  bands  is  not 
fully  understood,  but  it  has  been  assumed  that  they  serve  to  protect 
the  true  vocal  cords  against  injury  and  excessive  vibration.  In  the 
second  place,  it  is  held  that  they  serve  as  sphincters  of  the  larynx, 
their  approximation  tending  to  render  the  corresponding  movement 


GENERAL  ARRANGEMENT  OF  THE  PHONATING  ORGANS   545 


of  the  true  vocal  cords  more  eflfective.  Special  use  is  made  of  this 
mechanism,  in  conjunction  with  the  closure  of  the  epif^lottis,  whenever 
lar^e  amounts  of  air  are  to  bo  temj^orarily  retained  in  the  lungs,  or 
when,  as  in  running,  the  outflow  of  the  exjjiratory  air  is  to  he  retarded. 
Thirdly,  inasmuch  as  their  mucous  covering  contains  numerous  mucous 
and  serous  glands,  it  is  also  believed  that  they  furnish  the  moisture 
necessary  to  keep  the  vocal  cords  in  a 
proper  condition  for  vibration.  This  secre- 
tion is  temporarily  retained  in  the  cai)illary 
space  between  the  true  and  false  cords  and 
is  in  this  way  protected  against  evaporation. 
In  some  of  the  lower  animals,  these  spaces 
which  are  called  the  ventricles  of  Morgagni, 
are  very  commodious  and  are  constructetl 
in  such  a  way  that  they  may  serve  as  reso- 
nating chambers.  This  peculiarity  in  their 
general  arrangement  has  led  to  the  belief 
that  they  tend  to  augment  the  vibration  of 
the  true  vocal  cords. 

The  Tension  of  the  True  Vocal  Cords. 
— The  thyroid  and  cricoid  cartilages  arti- 
culate by  means  of  a  simple  bilateral  joint, 
the  axis  of  which  is  placed  transversely. 
Arising  upon  the  anterolateral  aspect  of 
the  cricoid,  a  small  conical  muscle,  known  as 
the  cricothyroid,  passes  upward  and  back- 
ward to  be  inserted  upon  the  lower  edge 
of  the  alse  of  the  thyroid  (Fig.  270).  Its 
function  is  to  diminish  the  height  of  the 
space  between  the  inferior  border  of  the 
thyroid  and  the  upper  border  of  the  cricoid 
cartilages.  This  end  it  attains  by  depress- 
ing the  former  and  raising  the  latter.  The 
result  of  this  movement  is  made  evident 
immediately  if  it  is  noted  that  these  car- 
tilages are  hinged  posteriorly  (R)  and  that 
the  arytenoids  (A),  which  are  situated 
transversely  upon  the  tips  of  the  cricoid  pro- 
cesses, are  thereby  moved  farther  backward. 
It  will  be  remembered  that  the  vocal  cords 
(VC)  are  attached  to  the  anterior  tips  of 

these  cartilages  and  extend  from  here  directly  across  the  cavity  to  be 
inserted  upon  the  anterior  wall  of  the  larynx.  Obviously,  therefore, 
since  the  approximation  of  the  thyroid  and  cricoid  cartilages  increases 
the  distance  between  the  vocal  processes  of  the  arytenoids  and  the 
anterior  wall  of  the  larynx,  these  bands  must  be  put  on  the  stretch. 
Thus,  it  is  evident  that  the  aforesaid  muscle  serves  as  the  tensor  of 

35 


W~ 


"iilJi 


Fig.  270. — Lateral  View 
OF  Larynx  to  Illustrate  the 
Action  of  the  Cricothyroid 
Muscle. 

H,  hyoid  bone;  M,  thyro- 
hyoid membranes;  PA,  po- 
mum  Adami;  T,  thyroid  carti- 
lage; C,  cricoid  cartilage;  Tr, 
trachea;  CT,  cricothyroid 
muscle;  P,  vertical  plate  of 
cricoid  with  {A)  arytenoid 
cartilages  placed  transversely 
upon  its  articulating  processes; 
VC,  vocal  cords;  R,  imaginary 
center  of  rotation  of  cricoid. 
When  cricothyroid  muscle  con- 
tracts, T  and  C  are  brought 
closer  together,  while  A  is 
forced  away  from  PA. 


546  VOICE    AND    SPEECH 

the  vocal  cords,  and  that  the  mechanism  just  described  is  the  one 
ordinarily  made  use  of  in  raising  the  pitch  of  the  sounds.  The  ap- 
proximation of  these  cartilages  may  be  felt  by  placing  the  finger  in 
the  notch  below  the  pomum  Adami  while  sounds  of  different  pitch 
are  produced.  In  the  human  larynx,  the  vocal  cords  are  penetrated 
by  a  few  muscle  fibers  which  take  their  origin  upon  the  arytenoid 
cartilages  and  eventually  reach  the  anterior  wall  of  the  larynx. 
Their  contraction  is  said  to  render  the  vocal  cords  more  tense  and 
hence,  this  muscle,  which  is  known  as  the  tensor  vocalis,  is  com- 
monly regarded  as  an  aid  to  the  cricothyroid.  Griitzner,^  on  the 
other  hand,  believes  that  its  contraction  renders  these  bands  more 
flabby  and  forms,  therefore,  a  typical  detentioner.  Nagel^  adheres 
to  the  first  view  and  states  that  these  muscle  fibers  antagonize  the 
lateral  displacement  of  the  edges  of  the  vocal  cords,  thereby  retain- 
ing them  more  fully  in  the  path  of  the  expiratory  currents  of  air. 

The  Approximation  of  the  Vocal  Cords. — As  has  been  stated  above, 
the  musculature  of  the  larynx  is  arranged  in  a  manner  to  form  a  sphinc- 
ter for  the  upper  end  of  the  respiratoiy  passage,  the  closure  of  which 
is  really  effected  at  three  different  levels,  namely,  at  the  epiglottis,  at 
the  false  vocal  cords  and  at  the  true  vocal  cords.  The  first  two  actions 
having  been  discussed,  we  are  now  in  a  position  to  analyze  the  third, 
namely,  the  adduction  and  abduction  of  the  vocal  cords. 

The  aiytenoid  cartilages  are  two  triangular  platelets  which  are 
placed  transversely  upon  the  tips  of  the  cricoid  processes.  They 
attain  their  greatest  width  posteriorly,  while  their  tapering  extremities 
or  vocal  processes,  are  directed  forward  to  serve  as  points  of  attach- 
ment for  the  vocal  cords.  Furthermore,  while  their  anterior  processes 
are  freely  movable  in  a  transverse  direction,  their  basal  portions  are 
relatively  fixed,  because  they  form  articulations  with  the  vertical 
plates  of  the  cricoid  cartilages.  The  latter,  as  has  been  shown  by 
Stieda  and  Will,^  are  prolonged  upward  into  two  small  cylindrical 
projections,  the  convex  surfaces  of  which  are  turned  upward  to  fit 
into  corresponding  concavities  upon  the  under  surfaces  of  the  aryte- 
noid cartilages.  These  joints  are  adjusted  in  such  a  way  that  the  out- 
ward movement  or  abduction  of  the  vocal  processes  necessitates  a  slight 
elevation  of  these  cartilages,  while  their  inward  movement,  or  adduction, 
permits  them  to  reassume  their  former  low  level.  By  inference,  it 
may  then  be  concluded  that  the  adduction  of  the  arytenoid  processes 
brings  the  vocal  cords  closer  together,  while  their  abduction  separates 
them  more  widely.  Consequently,  the  glottis  assumes  a  mere  slit- 
like outline  during  the  former  movement  and  a  typical  V-shaped 
outline  during  the  latter.  It  should  also  be  observed  that  the  approxi- 
mation of  the  vocal  cords  is  greatly  facilitated  by  an  inward  movement 

1  Ergebn.  der  Physiol.,  i,  1902,  466. 

2  Handb.  der  Physiol.,  iv,  1909,  702. 
^  Dissertation,  Konigsberg,  1895. 


GENERAL  ARRANGEMENT  OF  THE  PHONATING  ORGANS   547 

of  the  arytonoicl  cartilages  as  a  whole,  which  brings  their  posterior 
extremities  closer  together. 

The  muscles  involved  in  this  process  belong  to  the  intrinsic  group 
of  the  laryngeal  musculature,  and  present  the  .following  individual 
actions: 

(a)  The  -posterior  crico-arytenoid  muscle  arises  from  the  posterior  surface  of  the 
quadrate  plate  of  the  cricoid  cartilage  on  either  side  of  the  median  line  and  passes 
obliquely  upward  and  outward  to  be  inserted  upon  the  external  angle  of  the 
muscular  process  of  the  arytenoid  cartilage  (Fig.  271,  1).  Its  chief  action  is  to 
rotate  the  vocal  process  of  the  corresponding  arytenoid  upward  and  outward  so 
that  the  glottis  is  widened.     This  muscle,  therefore,  abducts  the  vocal  cords. 

(b)  The  lateral  crico-arytenoid  muscle  takes  its  origin  upon  the  upper  })order  of 
the  cricoid  cartilage  and,  passing  upward  and  backward,  Is  inserted  upon  the 
forepart  of  the  muscular  process  of  the  arytenoid  (Fig.  271,  2).  Its  contraction 
gives  rise  to  an  inward  and  downward  movement  of  the  vocal  process,  insuring 
thereby  an  adduction  of  the  vocal  cords  chiefly  at  their  posterior  ends. 


B 

Fig.  271. — Diagram  Illustrating  the  Abduction  and  Adduction  of  the  Vocal  Cords. 
A,  adduction;  1,  point  of  insertion  of  the  pcfst.  crico-arytenoid  muscle;  G,  glottis;  B, 
adduction;  2,  points  of  insertion  of  the  lat.  crico-arytenoid  and  thyro-arytenoid  muscles; 
3,  point  of  insertion  of  the  arytenoid  muscles.  The  dot  indicates  the  position  of  the 
center  of  rotation  of  the  arytenoid  cartilages. 

(c)  The  thyro-arytenoid  muscle  extends  between  the  inner  surface  of  the  thyroid 
cartilage,  post-external  to  the  median  line,  and  the  anterior  margin  and  external 
angle  of  the  arytenoid.  Its  inner  fibers  lie  in  close  relation  to  the  vocal  cords  and 
are  frequently  designated  as  the  musculus  vocalis.  When  contracting,  this  muscle 
rotates  the  corresponding  arytenoid  cartilage  around  its  vertical  axis,  drawing  the 
vocal  process  forward  and  inward.  It  acts,  therefore,  as  an  aid  to  the  lateral 
crico-arytenoid  muscle  in  causing  the  adduction  of  the  vocal  cords. 

(d)  The  arytenoid  muscle  extends  from  side  to  side,  joining  the  two  arytenoid 
cartilages.  It  consists  of  two  groups  of  fibers,  one  of  which  is  directed  horizontally 
across  the  median  line  and  the  other  obliquely  (Fig.  271,  3).  The  ends  of  the 
former  are  fastened  to  the  outer  margins  of  the  arytenoids  on  each  side,  while  the 
latter  unite  the  outer  angle  of  one  with  the  apex  of  the  other.  Obviously, 
these  fibers  have  to  do  with  the  approximation  of  the  posterior  ends  of  the  ary- 
tenoid cartilages,  lessening  the  length  of  the  rima  glottidis. 

The  Innervation  of  the  Larynx. — The  nerve  supply  of  the  larynx 
is  derived  from  the  systems  of  the  right  and  left  vagi  nerves.     The 


548  VOICE    AND    SPEECH 

particular  branches  which  govern  the  function  of  this  organ  are  the 
superior  and  inferior  laryngeal  nerves  (Fig.  263).  In  general  it  may 
be  said  that  their  innervation  is  unilateral  in  character,  but  a  slight 
median  overlapping,  especially  with  regard  to  the  sensory  fibers,  is 
not  uncommon.  It  has  been  shown  above  that  the  superior  branches 
are  motor  as  well  as  sensory  in  their  function,  while  the  inferior  or 
recurrent  branches  are  wholly  motor.  The  motor  qualities  of  the 
former  are  restricted  to  their  rami  externi  which  supply  the  crico- 
thyroid muscles.  These  muscles,  as  we  have  just  seen,  govern  the 
vertical  approximation  of  the  thyroid  and  cricoid  cartilages  and  deter- 
mine, therefore,  the  tension  of  the  vocal  cords.  Consequently,  it  may 
be  stated  that  the  inferior  branches  control  all  the  muscles  of  the  larynx 
with  the  exception  of  the  cricothyroids. 

Keeping  these  facts  clearly  in  mind,  it  must  be  evident  that  the 
stimulation  of  the  intact  superior  laryngeal  nerve,  or  of  the  distal 
end  of  the  divided  nerve,  leads  to  an  approachment  of  the  thyroid  and 
cricoid  cartilages  and  an  increased  tension  of  the  vocal  cords.  The 
glottis  is  slightly  narrowed  by  this  action,  owing  to  the  fact  that  the 
arytenoid  cartilages  are  not  sufficiently  resistant  to  withstand  the  pull 
exerted  by  the  vocal  cords.  The  cricothyroid  muscle  as  such,  however, 
does  not  serve  as  an  adductor  of  the  vocal  cords.  As  has  been  stated 
in  one  of  the  preceding  paragraphs,  the  sensory  qualities  of  this  nerve 
may  be  "ascertained  by  the  stimulation  of  the  intact  nerve  or  of  its 
central  end.  With  currents  of  moderate  strength,  this  procedure 
evokes  a  respiratory  standstill  and  forced  expiratory  blasts. 

Certain  evidence  has  been  presented  to  show  that  the  inferior 
laryngeal  nerve  of  the  apes  also  conducts  in  an  afferent  direction.  This 
is  also  true  of  the  corresponding  nerve  in  the  dog  and  cat,  but  only 
under  special  conditions.  In  view  of  this  uncertainty,  it  seems  best 
to  regard  this  nerve  essentially  as  a  motor  path  for  those  impulses 
which  give  rise  to  the  different  sphincter  actions  of  the  larynx,  and 
especially  to  that  occurring  at  the  level  of  the  vocal  cords.  Attention 
should  also  be  called  to  the  fact  that  the  vagus  innervates  extensive 
segments  of  the  pharynx  and  esophagus  and  is  thus  placed  in  a  position 
to  correlate  the  action  of  the  laryngeal  musculature  with  that  of  the 
muscles  used  during  the  process  of  deglutition.' 

In  accordance  with  these  statements,  it  may  be  concluded  that 
the  division  of  either  inferior  laryngeal  nerve  must  lead  to  a  paralysis 
of  the  muscles  on  the  corresponding  side  of  the  larynx,  excepting,  of 
course,  the  cricothyroid  muscle.  Quite  similarly,  the  division  of 
both  nerves  must  result  in  a  bilateral  paralysis,  the  aforesaid  muscles 
being  excepted.  In  young  animals,  this  procedure  is  usually  followed 
by  serious  symptoms,  death  from  asphyxia  resulting  in  the  course 
of  a  few  days.  But,  while  it  is  true  that  the  vocal  cords  assume  an 
extreme  median  position  in  consequence  of  the  paralysis  of  the  aryte- 
noid muscles,  this  condition  cannot  be  regarded  as  the  sole  cause  of 

1  Schultz  and  Dorendorf,  Archiv  fvir  Laryngologie,  xv,  1904. 


PRONATION  549 

death.  Account  must  also  be  taken  of  the  fact  that  the  accompanying 
paralysis  of  the  esophageal  musculature  leads  to  an  accumulation  of 
food  and  fluids  which  eventually  find  their  way  into  the  respiratory 
channel.  Consequently,  the  division  of  the  inferior  laryngeal  nerves 
paralyzes  that  mechanism  by  means  of  which  the  lungs  are  ordinarily 
protected  against  foreign  bodies  and  injurious  emanations.  Suffo- 
cation or  pneumonic  conditions  are  the  usual  outcome  of  this  defect. 
Vei-y  shnilar  results  may  be  obtained  by  the  division  of  the  superior 
laryngeal  nerves,  because  this  procedure  blocks  those  afferent  impulses 
which  normally  evoke  the  act  of  coughing,  thereby  dislodging  the 
foreign  material  from  the  larynx. 

By  selecting  the  highway  of  the  vagus,  these  sensory  impulses 
eventually  reach  the  nucleus  of  this  nerve  in  the  medulla,  whence  they 
are  relayed  to  other  centers  and  finally  to  the  motor  area  in  the  cere- 
bral cortex.  Those  movements  of  the  larynx  which  are  associated 
with  respiration,  are  automatically  controlled  by  a  center  situated  in 
the  medulla  and  closely  allied  to  the  respiratory  center.^  Motor 
points  for  the  laryngeal  muscles  have  been  isolated  by  Krause-  in 
the  gyrus  praefrontalis.  It  will  be  pointed  out  later  on  during  the 
discussions  upon  cerebral  localization,  that  these  motor  points  are 
under  the  control  of  a  psychic  center  for  phonation  and  speech,  which 
is  situated  in  part  in  the  left  inferior  frontal  convolution. 


CHAPTER  XLIV 
PHONATION 


In  order  to  be  able  to  produce  a  sound,  it  is  necessary  to  be  in 
possession  of  a  vibrating  body  the  constituents  of  which  may  be  set  into 
an  alternating  motion  by  some  external  force.  In  the  higher  animals, 
the  chief  vibrating  bodies  are  the  vocal  cords,  while  the  power  to  make 
them  oscillate  is  most  commonly  supphed  by  an  expiratory  blast  of  air 
which  may  be  softened  or  intensified  by  muscular  activity.  Moreover, 
since  these  expiratory  blasts  are  directed  not  only  against  the  vocal 
cords  but  also  against  other  mucous  folds  and  membranous  septa, 
noises  and  sounds  of  practically  all  descriptions  may  be  obtained. 
It  is  true,  however,  that  those  sounds  which  are  ordinarily  coordinated 
into  speech,  are  chiefly  dependent  upon  the  vibration  of  the  vocal 
cords,  while  the  parts  above  and  below  them  serve  merely  to  modify 
the  primary  sound.  In  this  regard  man  possesses  a  decided  advantage, 
because  the  different  parts  of  the  human  laiynx  are  more  delicately 
adjusted  and  are  under  the  direct  control  of  an  intricate  system  of  motor 

^  Grossman,  Zentralbl.  fiir  Physiol.,  iii,  1889. 
2  Archiv  fiir  Anat.  und  Physiol.,  1884. 


550 


VOICE    AND    SPEECH 


and  sensory  centers.  Thus,  the  production  of  coordinate  vocal  sounds 
is  really  a  distinguishing  characteristic  of  man;  no  other  animal  can 
at  all  equal  his  power  of  phonation.^  Some  seemingly  authentic 
cases,  however,  are  on  record  which  show  that  speech  of  a  very  crude 
and  limited  type  may  also  be  acquired  by  other  mammals,  and  quite 
aside  from  the  "talking  horse"  and  "talking  dog,"  it  seems  that  the 
monkeys  and  apes  have  a  limited  register  of  words,  conveying  different 
meanings. 

The  Examination  of  the  Larynx  in  Reflected  Light.  ^ — In  animals 
the  play  of  the  laryngeal  parts  may  be  studied  without  much  difficulty 
by  direct  inspection.  A  transverse  incision  having  been  made  between 
the  hyoid  bone  and  the  upper  edge  of  the  thyroid  cartilage,  the  larynx 
is  raised  upward  and  tilted  sufficiently  to  allow  an  unobstructed  view 


Lamp 


Concave  H/'rror 


Larynx. 


Fig.  272. — Diagram  op  Laryngoscope.     (From  Stewart's  "A   Manual  of  Physiology. 
William  Wood  and  Co.,  Publishers.) 


of  the  supraglottic  cavity  and  especially  of  its  floor  formed  by  the 
vocal  cords.  Killian^  has  devised  a  method  of  transillumination 
by  means  of  which  the  larynx  may  be  projected  in  magnified  form 
upon  a  screen.  The  human  larynx  may  be  inspected  with  the  help  of  a 
small  plane  mirror  which  is  mounted  upon  a  handle  and  is  placed  ob- 
liquely against  the  uvula.  A  beam  of  light  is  then  reflected  upon  it 
from  a  head  mirror  (Fig.  272),  The  observer  looking  through  a  small 
central  opening  in  the  latter,  obtains  an  image  of  the  parts  below,  but 
those  normally  situated  in  front,  appear  in  the  picture  to  be  located 
behind,  and  vice  versa. 

The  white  ghstening  vocal  cords  are  sharply  outHned  against  the 
red  mucous  lining  of  the  rest  of  the  laryngeal  wall  (Fig.  268).     During 

^  Mott:  The  brain  and  the  voice  in  speech  and  song,  New  York,  1910,  and 
Aikin,  The  voice,  an  introduction  to  practical  phonology,  London,  1910. 

-  First  successfully  undertaken  in  1854  by  M.  Garcia,  a  teacher  of  singing. 
In  1857  Tiirck  employed  this  method  upon  his  patients  in  Vienna. 

3  Miinchener  klin.  Wochenschr.,  No.  6,  1893. 


PHONATION  551 

quiet,  rospinition,  the  glottis  is  moderately  large,  becoming  small<!r 
on  expiration.  Moreover,  by  foreed  inspiratory  efforts,  tlie  ami  of 
this  communication  may  be  increased  in  such  a  measure  that  the  upper 
rings  of  the  trachea,  and  even  the  bifurcation  of  the  bronchi,  are  brought 
into  view.  Movements  of  the  vocal  cords  also  result  in  conseciu(!nce 
of  various  accessory  respiratory  efforts,  such  as  are  made  necessary 
during  the  acts  of  coughing,  sneezing,  and  hiccoughing. 

The  production  of  sounds  requires  not  only  a  varying  approximation 
of  the  vocal  cords,  but  also  a  very  precise  adjustment  of  their  tenseness. 
The  former  effect  which,  as  has  been  pointed  out  above,  is  based 
upon  the  rotation  of  the  arytenoid  cartilages  around  their  vertical 
axes,  seems  to  constitute  a  more  accurate  mechanism  than  the  latter 
which  is  largely  dependent  upon  the  backward  movement  of  these 
cartilages  in  consequence  of  the  contraction  of  the  cricothyroid 
muscles. 

The  different  laryngeal  parts  having  been  properly  set,  the  air 
stored  in  the  lungs  is  forced  outward  through  the  narrow  glottis, 
thereby  imparting  a  vibratory  motion  to 
the  vocal  bands.  In  order  to  overcome 
the  resistance  interposed  at  this  level,  it 
has  been  found  that  the  air-pressure  in  the 
trachea  necessary  to  cause  a  sound  of  ordi- 
nary pitch  and  loudness,  must  be  raised 
to  between  140  and  240  mm.  of  water. 
Loud  sounds  require  a  pressure  of  as  much 
as  950  mm.  of  water.  It  should  also  be 
remembered  that  the   vibrations   are   not    ^,  -^^^A  2  7  3  .—Position   of 

,  ,  ,  -  ,  Vocal    Cords   on    Uttering    a 

restricted  to  the  vocaf  cords,  but  are  atso    high  Note.    (Landois.) 
transferred  to  the  air  contained  in  the  outer 

respiratory  passage  as  well  as  to  that  filling  the  trachea  and  bronchi. 
Thus,  we  speak  of  a  chest  voice  and  a  falsetto  voice.  Chest  sounds 
always  impart  a  fremitus  to  the  wall  of  the  thorax  which  may  be 
perceived  by  placing  the  hands  over  the  lower  air-passage,  from  which 
the  resonance  is  obtained.  Falsetto  sounds  derive  their  resonance 
principally  from  the  pharyngeal,  oral  and  nasal  cavities.  In  general, 
therefore,  it  may  be  said  that  the  vocal  mechanism  embraces:  (1) 
the  motive  expiratory  blast  of  air,  (2)  the  larynx  which  gives  rise 
to  the  fundamental  sound,  (3)  the  thorax,  pharynx,  mouth  and  nose 
which  modify  the  primaiy  sound  and  give  color  to  it,  and  (4)  the 
organs  employed  in  articulating  the  sounds. 

The  Characteristics  of  Sounds. — The  action  of  the  vocal  cords 
may  be  imitated  in  a  crude  way  by  placing  a  short  tube  of  a  diameter 
of  about  2  cm.  against  the  palmar  surfaces  of  two  adjoining  fingers. 
By  blowing  into  the  free  end  of  this  tube  a  sound  will  be  produced 
in  consequence  of  the  vibrations  of  the  folds  of  skin  along  the  two  fingers. 
A  similar  purpose  is  served  by  the  so-called  artificial  larynx  which 
consists  of  a  piece  of  tubing,  one  end  of  which  is  partially  closed  by 


552  VOICE    AND    SPEECH 

two  bands  of  animal  membrane.  Appliances  of  this  kind,  however, 
do  not  give  a  correct  picture  of  the  action  of  the  vocal  cords,  because 
the  vibratory  parts  of  these  models  consist  of  closely  approximated 
bihpped  membranes  which  oscillate  toward  one  another.  Never- 
theless, they  serve  the  useful  purpose  of  demonstrating  that  the  vocal 
sounds,  in  agreement  with  the  sounds  produced  by  any  musical  in- 
strument, differ  from  one  another  in  loudness,  pitch  and  quality. 

The  loudness  or  intensity  of  a  sound  is  determined  by  two  factors, 
namely,  the  volume  and  force  of  the  expiratory  blast  of  air  and  the 
amplitude  of  the  vibrations  of  the  vocal  bands  in  either  direction  from 
their  position  of  rest  or  equihbrium.  These  vibrations,  moreover,  are 
greatly  reinforced  by  the  sympathetic  oscillation  of  the  walls  of  the 
chest  and  head  parts. 

The  pitch  of  a  sound  depends  upon  the  number  of  vibrations  oc- 
curring in  a  unit  of  time.  Obviously,  therefore,  it  is  determined  first 
of  all  by  the  character  of  the  vibrating  body,  i.e.,  by  the  length, 
thickness  and  general  elastic  qualities  of  the  vocal  cords.  Secondly, 
it  is  dependent  upon  the  degree  of  tension  to  which  these  bands  are 
subjected,  the  highest  sounds  being  emitted  when  they  are  tightly 
stretched  beside  a  narrow  glottis.  As  a  rule,  the  outline  of  the  latter 
remains  elliptical  as  long  as  the  vibrations  do  not  exceed  240  to  the 
second.  Between  240  and  512  vibrations,  on  the  other  hand,  the  vocal 
bands  are  gradually  brought  closer  together  until  they  eventually  en- 
velop merely  the  narrowest  possible  sht.  In  fact,  the  production  of 
very  high  notes  requires  an  almost  absolute  approximation  of  these 
bands  so  that  only  short  segments  of  them  are  allowed  to  vibrate.  At 
this  time,  the  vocal  aperture  or  rima  vocalis  is  restricted  to  a  small  oval 
opening  situated  directly  behind  the  anterior  wall  of  the  thyroid 
cartilage. 

The  foregoing  very  general  reference  to  the  structural  peculiarities 
of  the  vocal  cords  may  serve  as  an  explanation  for  the  differences 
in  the  pitch  and  quality  of  the  voice  in  men  and  women.  Since  the 
vocal  bands  of  children  are  relatively  short,  the  pitch  of  their  voice 
must  be  high.  At  puberty,  however,  the  larynx  develops  very  rapidly 
in  both  sexes,  a  fact  which  readily  accounts  for  the  rather  sudden 
drop  in  the  pitch  of  the  voice  occurring  at  this  time.  Moreover, 
owing  to  the  fact  that  the  cords  attain  a  greater  length  in  men,  this 
"breaking"  of  the  voice  is  especially  pronounced  in  them.  In  most 
instances,  the  voice  of  women  acquires  at  this  time  merely  a  fuller 
and  richer  character.  If  the  development  of  distinct  sex  character- 
istics is  prevented  by  castration  or  by  disturbances  in  the  function 
of  the  internal  secretory  organs,  the  larynx  fails  to  undergo  these 
changes  and  the  voice  retains  its  peculiar  high  pitch  and  immature 
quality. 

The  quality  of  the  sounds  depends  upon  the  character  of  the  vibra- 
tions. Like  in  any  musical  instrument,  the  vibrations  of  the  vocal 
cords  are  of  the  composite  type,  i.e.,  they  are  made  up  of  fundamental 


PRONATION  553 

and  secondary  oscillations.  In  tho  first  instance,  the  cords  as  a  whole 
swing  to  anfl  fro,  while  in  the  second,  only  short  segments  of  them 
are  made  to  vibrate.  In  this  way,  the  fundamental  tone  is  constantly 
combined  with  secondary  partial  tones  or  overtones.  Besides,  the 
laryngeal  sounds  are  qualificxl  by  the  resonance  of  the  chambers 
situated  above  and  bellow,  and  especially  by  the  oral  and  nasal  cavities. 

The  Peculiarities  of  Voc£il  Sounds. — The  musical  sounds  which 
we  are  capable  of  producing,  do  not  shade  evenly  into  one  another 
from  the  lowest  to  the  highest,  but  appear  in  groups,  i.e.,  a  number  of 
them  always  possess  a  quality  which  is  often  sharply  differentiated 
from  that  of  the  neighboring  group.  We  speak,  therefore,  of  vocal 
registers,  but  it  must  be  remembered  that  the  "breaks"  between 
these  may  be  rendered  less  conspicuous  by  training.  It  is  commonly 
stated  to-day  that  the  range  of  the  voice  embraces  two  registers,  namely, 
the  chest  voice  and  the  falsetto.  Some  authors  also  recognize  a  third, 
or  middle  register,  and  some  even  a  fourth.  As  may  be  surmised, 
these  differences  depend  upon  modifications  in  the  use  of  the  resonating 
parts.  The  chest-register  is  the  lowest  and  is  produced  by  a  pro- 
nounced vibration  or  fremitus  of  the  wall  of  the  thorax.  It  is  richer 
in  overtones,  and  requires  somewhat  smaller  quantities  of  air,  because 
the  vocal  bands  are  more  closely  approximated  than  they  are  during  the 
production  of  the  falsetto  or  head-notes.  Inasmuch  as  the  latter 
depend  principally  upon  the  resonance  of  the  cavities  of  the  head, 
their  production  requires  a  copious  supply  of  air  which  is  made  to 
escape  through  the  anterior  part  of  the  rima  glottidis,  while  the  posterior 
portion  of  the  glottic  space  remains  closed. 

A  fundamental  difference  between  the  voice  used  in  talking  and 
that  employed  in  si?iging,  does  not  exist.  During  singing,  however, 
certain  qualities  of  the  sounds  are  intensified  chiefly  by  rendering 
the  path  of  the  sound-waves  perfectly  free  so  that  they  are  enabled  to 
attain  sonority  and  a  greater  penetrating  power.  This  is  especially 
true  of  the  vowels,  the  fundamental  note  of  which  is  always  protected 
as  much  as  possible  against  admixtures  or  formants.  Moreover,  in 
singing,  the  individual  notes  are  not  maintained  for  so  long  a  time  as 
in  talking. 

Under  ordinary  conditions  the  range  of  the  singing  voice  extends 
over  two  octaves,  but  it  can  be  considerably  increased  by  training  so 
that  it  finally  embraces  3  or  3}^^  octaves.^  In  lohis'pering  the  vibra- 
tions of  the  vocal  cords  are  displaced  by  friction  sounds  produced 
along  the  laryngeal  and  buccal  pharyngeal  walls.  The  vocal  bands 
are  rather  relaxed  at  this  time,  while  the  glottis  is  made  to  assume  an 
intermediate  size. 

Speech  is  articulated  voice.  The  voice  sounds  are  modified  by  the 
resonance  of  the  different  chambers  and  are  combined  with  noises 

^  Gutzmann,  Stimmbildunp;  und  Stimmpflege,  Wiesbaden,  1906;  also  Roudet, 
Elements  de  phonetique  generale,  Paris,  1911. 


554  VOICE    AND    SPEECH 

produced  outside  the  larynx.  Thus,  we  obtain  vowels  or  sonants 
and  consonants.  The  former  are  dependent  upon  the  vibrating  quali- 
ties of  the  vocal  cords  and  are,  therefore,  musical  sounds,  while  the 
latter  are  noises  caused  by  irregular  oscillations  of  the  mouth  parts. 
One  of  these  extralaryngeal  constrictions,  against  which  the  ex- 
piratory current  of  air  is  forced,  is  formed  by  the  lips,  another  by 
the  teeth  and  the  tongue  and  still  another,  by  the  soft  palate  and  the 
tongue. 

While  the  fundamental  character  of  the  vowels  is  determined  by  the 
vibration  of  the  vocal  cords,  a  special  quaUty  is  imparted  to  them  by 
the  varied  resonance  of  the  oral  cavity.  Such  factors  as  the  size  and 
shape  of  this  cavity,  the  position  of  the  tongue  and  the  shape  of  the 
soft  palate  play  a  part  in  their  formation.  Their  influence  is  chiefly 
directed  toward  the  reinforcement  of  certain  overtones.  This 
view  which  is  essentially  the  one  advocated  by  Helmholtz,^  has  been 
modified  somewhat  by  Hermann,^  who  claims  that  the  mouth  does  not 
act  as  a  mere  resonator,  but  actually  gives  rise  to  secondary  musical 
notes  which  need  not  be  harmonics  of  the  laryngeal  sound. 

As  has  just  been  stated,  the  consonants  are  produced  by  the  various 
constrictor  adjustments  of  the  mouth-parts,  i.e.,  by  "  positions  of  articu- 
lation. "  In  accordance  with  the  seat  of  the  obstruction,  these  sounds 
are  classified  as  labials,  dentals,  gutturals  and  nasals.  Every  one  of 
them  may  be  characterized  as  soft  and  hard,  the  former  designation 
being  applied  to  them  if  they  are  formed  during  phonation  and  the 
latter  if  the  vocal  cords  do  not  take  part  in  their  production.  The 
sound  D,  for  example,  is  a  soft  dental  sound,  because  the  simultaneous 
vibration  of  the  vocal  cords  gives  it  quality,  while  the  sound  T  is  hard, 
because  it  is  a  pure  dental  sound  and  is  not  accompanied  by  phonation. 
Griitzner  has  divided  the  consonants  into  semivowels,  ex-plosive  and 
friction  sounds.  Among  the  first  may  be  mentioned  the  sounds  m,  n, 
ng,  I  and  r.  Thus,  if  sounded  in  part  through  the  nose,  as  "reso- 
nants, "  as  in  him,  hen,  or  being,  they  assume  the  character  of  vowels, 
because  they  are  produced  by  the  vibration  of  the  vocal  cords,  while 
the  air  is  forced  out  largely  through  the  nasal  cavity  imparting  to  them 
a  peculiar  nasal  resonance.  But  if  employed  as  real  consonants,  as 
in  make  or  no,  they  acquire  the  characteristics  of  explosive  sounds. 
Typical  explosives  are  the  sounds  p  and  v  (labials),  t  and  d  (Hnguo- 
palatals  or  dentals)  and  k  and  g  (gutturals).  They  are  said  to  be 
formed  with  or  without  voice,  because  the  production  of  some  of  them 
necessitates  a  vibration  of  the  cords,  for  example,  the  sounds  6,  d  and 
g.  Friction  sounds  or  frictionals,  are  produced  by  the  passage  of  the 
expiratory  air  across  the  edges  of  constricted  areas,  which  are  thereby 
thrown  into  vibration.  In  this  way,  there  are  produced  at  the  labio- 
dental communication  the  sounds  of/,  v,  and  w;  the  first  of  which  does 

1  Lehre  von  den  Tonempfindungen,  Braunschweig,  1877. 

2  Pfliiger's  Archiv,  xlvii,  1890,  44. 


PRONATION  555, 

not  require  voice,  while  the  other  two  do.  As  lingual  f rictional  may  he 
classified  such  sounds  as  s,  th,  sh,  ch,  z  andj,  the  production  of  the  last 
two  necessitating  phonation.  The  vibrative  r  is  produced  entirely 
with  the  tongue,  whiU^  h  finds  its  origin  at  the  pharyngeal  entrance. 
In  the  latter  case  the  mouth-parts  assume  the  position  ordinarily  re- 
quired to  utter  the  vowel  following  the  h,  as  in  hear  or  house. 


PART  V 
THE  CENTRAI.  XER\'OUS  SYSTEM 

SECTION  XIV 

THE  FUNCTIONAL  SIGNIFICANCE  OF  THE  NERVOUS 

SYSTEM 


CHAPTER  XLV 


THE     STRUCTURAL    ARRANGEMENT     OF    THE    NERVOUS 

SYSTEM 

The  Subdivisions  of  the  Nervous  System. — Topographically  the 
nervous  system  presents  itself  as  a  central  7nass,  consisting  of  the  cere- 
brum, cerebellum,  basal  ganglia,  medulla  and  spinal  cord,  and  a 
peripheral  complex,  formed  by  the  cranial,  spinal  and  sympathetic 
nerves.  The  latter,  of  course,  also  embraces  a  multitude  of  ganglia 
as  well  as  different  ramifications  in  the  form  of  plexuses  and  end-plates. 
For  structural  and  functional  reasons  the  nervous  system  is  commonly 
divided  into  a  cerebrospinal  system  and  a  sympathetic  or  autonomic 
system.  The  former  embraces  the  cerebrum,  cerebellum,  basal 
ganglia,  medulla,  spinal  cord,  and  the  cranial  and  spinal  nerves,  while 
the  latter  includes  the  different  sympathetic  and  parasympathetic 
ganglia  throughout  the  body  and  the  nerves  connecting  these  ganglia 
with  the  cerebrospinal  system.     This  division  is  based  upon : 

(a)  Anatomical  grounds,  in  that  the  gross  arrangement  of  the  sympathetic  sys- 
tem is  very  different  from  that  of  the  cerebrospinal,  consisting  as  we  shall  see  later, 
of  a  chain  of  ganglia,  which  begins  above  with  the  superior  and  inferior  cervical, 
and  the  superior,  middle  and  inferior  thoracic,  and  "ends  below  with  the  solar, 
and  the  pelvic  ganglia.  In  many  places  the  fibers  emerging  from  these  stations, 
ramify  very  extensively,  and  form  complex  networks,  or  plexuses. 

(6)  Histological  grounds,  in  that  the  sympathetic  ner\'e  fibers  are  non-medul- 
lated  and  connect  with  cells-bodies  possessing  a  very  characteristic  shape. 

(c)  Chemical  grounds,  in  that  the  mass  of  the  sympathetic  neurones  seems  to 
be  made  up  of  neuroplasm  which  is  somewhat  different  from  that  constituting  the 
cerebrospinal  neurones. 

{d)  Functional  grounds,  in  that  the  life  processes  regulated  by  the  sympathetic 
system  remain  for  the  most  part  subconscious.  For  this  reason,  sympathetic 
reactions  are  very  largely  non-volitional  and  reflex  in  their  nature. 

557 


558 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


g 


M: 


\\v 


r^."- 


The  Structural  Unit  of  the  Nervous  System. — In  conformity  with 
other  tissues,  nervous  tissue  is  composed  of  two  types  of  cells  which 
may  be  characterized  as  true  and  accessory.  The  former  are  called 
neurons  and  constitute  the  functional  element  of  this  tissue,  while  the 
latter  are  used  for  the  supporting  framework  composed  of  ependyma 
and  neuroglia  or  glia  cells.  It  is  true,  however,  that  these  cells  are 
indispensable  to  one  another,  i.e.,  one  cannot  in  all  probability  exist 

without  the  other,  but  looked 
at  in  a  general  way,  it  is  the 
neuron  which  attracts  our  atten- 
tion most,  because  it  is  more 
directly  concerned  with  nervous 
processes.  In  the  terminology 
of  Waldeyer,^  the  neuron  or 
nerve-cell  is  the  histological  unit 
of  the  nervous  system,  and  as 
such  includes  the  cell-body  as  well 
as  its  protoplasmic  processes, 
namely,  the  dendrites,  axis 
cylinder,  arborizations  and  col- 
laterals. Looked  at  in  this  way, 
the  nervous  system  consists  of 
enormous  numbers  of  neurons^ 
supported  by  glia  cells  and  en- 
veloped here  and  there  by  pro- 
tective membranes,  such  as  the 
dura  mater,  arachnoid  and  pia 
mater.  This  constitutes  the 
"neuron  concept"  of  the  nervous 
system.  We  shall  see  later  on 
that  the  structural  independence 
thus  granted  to  the  neuron,'  is 
associated  with  an  unmistakable 
physiological,  distinctiveness. 

The  External  Characteristics 

of    the    Neuron. — Neurons    are 

cells  modified  to  suit  a  particular 

purpose,  namely,  that  of  generat- 

NormalAnterior  Horn  Cell  Show-  ing  and  conducting   nerve   im- 

iWarrington.)     pulses.     They     are     in     reahty 

neuroplasmic    fibers    possessing 

an   accumulation   of   cytoplasm 

at  one  point  of  their  course  in  which  are  embedded  a  nucleus  and 

nucleolus.     In  this  regard  they  present  the  essential  details  of  a  cell, 

^  Deutsche  med.  Wochcnschr.,  xvii,  1891,  1244. 

2  KoUiker  objects  to  this  term  upon  philological  grounds  without,  however, 
furnishing  a  more  correct  or  convenient  concept. 


'% 


\ 


J 


//.'•' 

^ 


I 


FiQ.274 

ING   THE    NiSSL  GrAJTOLES. 

a,  The  Axon 


ARRANC.EMENT    OF    THE    NERVOUS    SYSTEM 


559 


because  they  eonsist  of  cytoplasm  and  niicl(^ar  material.  It  stands  to 
reason,  howevin-,  that  their  general  configuiation  must  be  subj(^ct  to 
marked  variations,  because  the  physiological  piocesses  for  which  they 
arc  destined,  necessitate  an  absolute  structural  adaptation  to  the 
conditions  existing  in  different  parts  of  the  body.  Thus  we  find  that 
while  nerve-cells  always  pr(>sent  the  characteristics  of  an  elongated 
conductor,  they  are  frequently  so  highly  modified  that  it  becomes 
difficult  to  recognize  their  true  nature.  Their  structural  wealth  has 
been  brought  out  more  especially  in  recent  years  as  a  result  of  more 
advanced  methods  in  fixing  and  staining.' 

It  is  now  commonly  believed  that  neurons  are  developed  from 
single  embryonic  cells  which  are  called  neuroblasts  (Fig.  275).  These 
precursors  are  compact  neuroplasmic 
masses,  possessing  a  round  or  oval 
shape  and  containing  a  well-defined 
nucleus  somewhere  near  the  center 
of  their  cytoplasm.  In  the  course 
of  time,  these  apolar  cells  become 
pear-shaped  and  finally  send  out  a 
process  which  renders  them  unipolar 
and  eventually  multipolar  in  char- 
acter. This  theory  of  His  has  been 
modified  in  more  recent  years^  by 
making  allowance  for  the  fact  that 
certain  fiber  paths  seem  to  be  de- 
veloped directly  from  the  neuro- 
blasts, i.e.,  the  latter  may  lose  their 
cellular  character  entirely  and  be 
converted  solely  into  axons.  Thus, 
a  number  of  neuroblasts  may  be 
joined  together  in  such  a  way  that 
a  conducting  path  is  produced  which 
is  then  united  with  other  neuroblasts  which  have  given  rise  to  cell- 
bodies. 

As  has  been  stated  above,  the  mature  neurons  present  such  a  wealth  of  struc- 
ture that  it  is  impossible  to  classify  them  satisfactorily.  Many  of  them,  however, 
present  a  very  characteristic  appearance,  enabling  us  to  recognize  them  immedi- 
ately. Cells  of  this  tj^pe  are  the  large  pyramidal  cells  of  the  motor  area  of  the 
cerebral  cortex,  the  bipolar  cells  of  the  sensory  ganglia,  the  fan-shaped  ceUs  of 
Purkinje  of  the  cerebellum,  and  others.  At  all  events,  any  attempt  at  classifica- 
tion must  take  cognizance  of  the  shape  and  size  of  the  cell-bodj^  and  of  the  number, 
size,  and  manner  of  branching  of  the  processes — axis  cylinder  and  dendrites  alike. 
The  shape  and  size  of  the  cell-body  varj'  considerably.     In  the  cerebral  cortex, 

1  Among  the  investigators  who  have  greatly  enhanced  our  knowledge  in  this 
regard,  might  be  mentioned  Ehrlich  (Deutsche  med.  Wochenschr.,  xii,  1886,  49), 
Apathy  (Proc.  Intern.  Zool.  Congress,  Cambridge,  1898),  Golgi  (Arch,  fisiol.,  iv, 
1897),  Nissl  (Die  Neuronenlehre,  etc.,  Jena,  1903),  and  Ramon  Y.  Cajal  (Hist,  de 
Systeme  Nerveux,  Paris,  1909). 

^  Baglioni,  Zur  Analyse  der  Reflexfunktion,  Wiesbaden,  1906. 


Fig.  275. — Growing  Nevroblasts. 

A,  Silver  method  of  Cajal;  B,  Golgi's 

method.     (Cajal.) 


560 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


for  example,  we  find  enormous  numl)ers  of  small  and  large  pyramidal  cells,  while 
those  constituting  the  spinal  ganglia,  are  spherical,  and  those  forming  the  ventral 
horn  of  the  gray  matter  of  the  cord,  rather  square  irregular.  Very  typical  flask- 
shaped  cells  are  found  in  the  ccrelxdlum.  Many  of  tliese  cell-bodies  are  visible 
to  the  naked  eye,  for  example,  those  of  the  cells  of  Purkinjc  (Fig.  276)  and  those 
situated  in  the  anterior  horns  of  the  gray  matter  of  the  cord  (150/x).  Others, 
again,  are  extremely  small,  measuring  only  from  4-9yU  in  diameter. 

The  large  pyramidal  cells  in  the  cerebral  cortex  (Fig.  277)  measure  from  20-30ju 
and  the  small  ones  from  IO-VZ/jl  in  diameter.  Among  the  smallest  are  those  com- 
posing the  olfactory  bidb,  and  those  forming  parts  of  the  cerebellum.  Neither  are 
we  in  a  position  to  give  definite  measurements  regarding  the  length  of  the  neuron 
as  a  whole,  because  the  distances  which  the  different  nerve  paths  must  cover,  vary 


Fig.  276. — Purkinjb  Cell  from  Human  Cerebellum. 
Golgi's  method  of  staining.     (Stohr.) 


very  greatly.  It  is  said,  however,  that  they  may  attain  a  length  of  1.0  m.,  bridging 
the  distance  between  the  motor  area  of  the  cerebrum  and  the  lumbar  region  of  the 
spinal  cord,  or  the  distance  between  the  latter  and  the  effectors  in  the  foot.  On 
the  afferent  side,  they  do  not  attain  so  great  a  length,  because  the  sensory  paths 
are  usually  beset  with  a  greater  number  of  relay  stations.  It  is  also  of  interest 
to  note  that  the  volume  of  the  axons  of  these  cells  greatly  exceeds  that  of  the 
cell-bodies.  In  large  motor  cells,  for  example,  the  axis  cylinder  plus  its  enveloping 
sheath,  possesses  a  volume  1500  times  greater  than  that  of  the  cell-body.  Golgi^ 
recognizes  three  types  of  cells,  namely: 

Type  1. — The  dendrites  are  short  and  ramify  in  close  proximity  to  the  cell-body. 
Broad  and  thick  at  their  origin,  they  gradually  become  thinner  as  they  divide  in  an 

1  Boll.  d.  Societa  Med.  Chir.  di  Pavia,  1898-1899. 


ARRANGEMENT    OF    THE    NERVOUS    SYSTEM 


561 


antlcr-likc  manner  into  tlu'ir  liiicst  tciniiiials.  ihw.  ul"  iJu)  dcndrilcs  Kt""-rsilly 
reaches  farther  into  the  surrouiuUnn  tissue  tlian  the  others.  These  cells  possess 
a  siuf^le  lon^  axon  and  serve,  therefore,  tlie  purpose  of  conveying  impulses  over  a 
lonji;  distance.  In  most  instances,  the  axon  finally  leaves  the-  central  system  and 
beconu>s  a  nerve  fiber,  terminating  eventually  in  an  end-organ.  Its  collaterals 
also  break  up  iii  arborizations.     Cells  of  this  kind  are  the  motor  neurons,  found  in 


Fig.  277. — A,  B,  C,  and  D,  PyRAMroAL  Cells  from  the  Motor  Area  of  Man. 
a,  b,  Spaces  which  are  filled  with  tigroid  bodies;  c,  pigment;  e,  nuclei  of  glia  tissue; 
/,  base  of  a  dendrite;  g,  h,  basal  portion  of  axons.     {Cajal.) 


the  cortex  of  the  cerebrum,  the  anterior  horn  cells  of  the  spinal  cord,  and  the  cells 
of  Purkinje  of  the  cerebellum.  Cells  of  this  kind  we  are  prone  to  picture  to  our- 
selves when  describing  a  neuron. 

Type  2. — This  cell  bears  the  same  characteristics  as  that  of  the  first  type,  but 
its  axon  is  short.     These  neurons,  therefore,  must  serve  the  purpose  of  conveying 

36 


562 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


impulses  from  place  to  place  within  the  realm  of  a  single  center.  For  this  reason, 
they  generally  remain  confined  to  the  central  nervous  system  and  serve  chiefly 
as  intermediate  conductors.  This  deduction  seems  the  more  correct,  because  their 
axon  usually  splits  into  several  branches  within  the  gray  matter,  thus  tending  to 
associate  its  different  areas.  The  first  and  second  types  of  Golgi  cells  are,  of  course, 
multipolar  in  character. 

Type  3. — This  cell  is  typically  represented  by  the  neurons  forming  the  ganglia 
upon  the  posterior  root  of  the  spinal  cord  and  the  ganglia  occurring  in  the  course 
of  the  sensory  branches  of  the  cranial  nerves.  In  lower  forms  (fish)  and  also 
in  the  mammalian  embryo,  the  cells  of  the  spinal  root  ganglion  possess  two  processes 
which  leave  at  opposite  poles  of  the  cell-body,  and  are,  therefore,  bipolar.  In  the 
adult  mammal,  however,  a  union  has  been  effected  between  them  so  that  they  now 
arise  as  one  (Fig.  278).     The  process  passes  away  from  the  cell-body  but  soon  di- 


FiG.  278. — Unipolar  Cells  of  the  Ga.sserun  Ganglion. 
At  a  is  shown  the  glomerulus  formation  of  the  axon.      (Cajai.) 


vides  into  two,  one  of  which  extends  into  the  posterior  realm  of  the  cord  and  the 
other  outward  to  the  corresponding  receptors.  This  peculiar  distribution  gives 
rise  to  a  unipolar  cell  with  a  T-shaped  process,  the  branches  of  which  become 
meduUated  and  serve  as  long  conducting  fibers.  It  is  questionable  whether  the 
impulses  conveyed  inward  from  the  distant  receptor,  must  first  of  all  enter  the 
cell-body  proper  before  they  can  be  transferred  to  the  central  branch.  In  fact, 
one  of  the  points  regarding  the  fibrillar  theory  to  be  discussed  later,  is  that  the 
cell-body  is  not  necessary  for  conduction.  It  may  be  removed  without  disturbing 
the  passage  of  these  afferent  impulses,  and  hence,  it  must  be  concluded  that  the 
dendrite-like  distal  branch  is  in  direct  functional  relation  with  the  axon-Uke 
central  branch. 


ARRANGEMENT    OF    THE    NERVOUS    SYSTEM  503 

The  Internal  Characteristics  of  the  Neuron.' — The  maturing  of 
the  ncrvi'-ci'U  necessitates  several  ciianges.  First,  we  have  the 
estabhslnnent  ol"  the  pohirity  of  the  cell,  i.e.,  the  neuroblast  sends 
out  an  axon,  which  is  soon  followed  by  the  formation  of  dendrites. 
In  some  cases,  these  processes  then  become  nieduUated  or  are  en- 
veloped solely  by  neurolemma;  or  both.     Wliilc  these  alterations  in 


.♦f:i3^^-' 


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A' 

iri  -- 

.X 

\f 

\ 

■.:\ 

V 

^  \ 

JV>-- 

:  .*•-■  -. " 

J-'-ll 
■  '/■'■ 


>«L> 


Fig.  279. — Cell  from  the  Anterior  Horn  of  the  Spinal  Cord  of  a  Rabbit, 

Showing  Nissl's  Bodies. 

Ax,  Axon;  D,  dendrite;  K,  nucleus;  A'',  nucleolus.      (Klopsch.) 

the  configuration  of  the  neuron  are  being  completed,  the  cytoplasm 
of  the  cell-body  becomes  more  highly  differentiated,  presenting  finally 
the  following  details: 

(1)  A  well  marked  nucleus  and  nucleolus  surrounded  by  a  relatively  thick  layer 
of  cytoplasm;  (2)   flake-like  masses  of  a  complex  protein  substance  chemically 

^  Nerve-cells  were  first  recognized  by  Ehrenberg,  in  1833,  in  the  spinal  ganglia 
of  the  frog.  In  1838,  Remak  established  the  fact  that  nerve  fibers  are  prolongations 
of  the  cell-bodies.  This  observation  was  made  upon  the  sympathetic  fibers  of 
invertebrates.  It  was  found  to  hold  true  in  mammals  by  Helmholtz  and  Hanover 
(1842).  In  1863  the  observations  of  Deiters  were  published  which  showed  that 
the  cells  of  the  central  nervous  system  possess  two  kinds  of  processes,  namely, 
protoplasmic  prolongations  and  a  real  fiber  process.  Gerlach  (1871),  Golgi  (1873) 
and  Ramon  Y.  Cajal  (1888),  furnished  additional  data  regarding  the  structure 
of  the  neuron. 


564  SIGNIFICANCE    OF   THE    NERVOUS    SYSTEM 

allied  to  chromatin  which  are  scattered,  through  the  cytoplasm  and  also  extend 
into  the  larger  dendrites  but  not  into  the  axon.  They  are  generally  designated 
as  Nissl's  granules  or  tigroid  bodies;  (3)  strands  of  denser  protoplasm  which 
traverse  the  cytoplasm  in  all  directions  making  connections  between  the  different 
processes  of  the  neuron.  They  do  not  invade  the  nuclear  substance.  These 
so-called  fibrillse  are  said  to  l)e  continuous  with  the  fibnllae  composing  the  axis- 
cylinder,  and  are  regarded  as  the  specific  conducting  element  of  the  neuron. 

To  be  sure,  these  characteristics  are  not  shown  by  all  nerve-cells, 
because  some  of  them  possess  very  small  amounts  of  cytoplasm; 
while  others  appear  to  be  composed  solely  of  nuclear  material.     NissP 


Fig.  280. — Normal  Nerve  Cell  fro.m  the  Lobus  Electricus  of  the  Torpedo.     (Garten.) 

who  has  made  an  exact  study  of  the  structural  details  of  the  different 
nerve-cells,  divides  them  into: 

1.  Somachrome  Cells. — The  cytoplasm  surrounding  the  nucleus,  exhibits  a  dis- 
tinct structure,  showing  thereby  that  it  possesses  a  decided  functional  importance. 
By  far  the  largest  number  of  nerve  cells  belong  to  this  group.  They  may  be  sub- 
divided further  in  accordance  with  the  staining  qualities  of  their  cytoplasm.  ^ 

2.  Cytochrome  Cells. — Their  cell-bodies  are  poorly  developed,  so  that  they 
seem  to  be  composed  of  naked  nuclei.  Cells  of  this  kind  are  present  in  the  sub- 
stantia gelatmosa  of  Rolando  and  in  the  granular  layer  of  the  cerebellum  and  olfac- 
tory lobe. 

1  Allg.  Zeitschr.  fiir  Psychiatric,  liv,  1897,  101. 

2  Barker.  The  Nervous  System,  New  York,  1899,  121. 


ARRANGEMENT    OF    THE    NERVOUS    SYSTEM  565 


CHAPTER  XL VI 

THE  FUNCTIONAL  ARRANGEMENT  OF  THE  NERVOUS 

SYSTEM 

The  Neuron  Doctrine. — While  the  histological  individuality  of  the 
neuron  has  been  founded  upon  the  work  of  many  investigators,  it  was 
left  to  Waldeyer^  to  correlate  the  facts  in  such  a  way  that  clearness 
was  finally  brought  into  the  chaos  of  nervous  elements  and  their  func- 
tion (1891).  In  accordance  with  the  views  of  this  investigator,  the 
neurons  are  to  be  regarded  as  the  building  stones  of  the  nervous  sys- 
tem, and  hence,  must  be  dealt  with  as  independent  cellular  units. 
This  implies  that  the  nervous  system  is  built  up  of  individual  neurons 
which  retain  a  definite  structural  relationship  to  one  another.  They 
are  connected  with  one  another  by  means  of  their  processes,  but  this 
connection  is  had  only  by  contact  and  not  by  confluence. 

We  have  noted  that  the  neuron  possesses  an  embryological  dis- 
tinctiveness in  the  form  of  the  neuroblast.  To  this  must  now  be 
added  its  specific  histological  and  anatomical  appearance  and  thirdly, 
also  a  definite  functional  independence.  The  sum  total  of  their 
individual  actions  gives  rise  to  the  complex  of  nervous  processes  as 
we  observe  them  in  the  higher  animals.  This  extension  of  the  neuron 
doctrine  to  function  followed  very  naturally  upon  the  establishment 
of  the  fact  that  neurons  are  structural  entities.  Physiologically,  the 
neuron  concept  tends  to  place  emphasis  upon  the  cytoplasm  and  nu- 
clear constituents  of  the  cell-body  rather  than  upon  the  conducting 
paths,  so  that  the  former  must  really  be  considered  as  the  directing 
element  of  the  whole. 

The  Fibrillar  Hypothesis. — Contrary  to  Waldeyer  and  his  followers, 
it  is  held  by  Nissl,^  Bethe,^  Apathy,'*  Schenck,^  and  Pflliger^  that 
the  nervous  system  is  made  up  of  conducting  strands  of  neuroplasm 
which  are  directly  continuous  with  one  another.  The  element  which  is 
thus  brought  into  prominence,  consists  of  the  neurofibrils  which,  as 
w^e  have  just  seen,  permeate  the  cytoplasm  of  the  cell-body  and  go 
to  form  the  dendritic  and  axon  processes  of  the  neuron.  In  accord- 
ance with  this  view,  the  structural  and  functional  unit  of  the  nervous 
system  is  formed  by  the  neurofibril.  Here  and  there  a  number  of 
these  fibrils  may  pursue  a  common  course  and  form  such  structures 

^  Deutsche  med.  Wochenschr.,  1891.  Also  see:  v.  Leuhoss^k,  Der  feinere  Bau 
des  Nervensystemes,  etc.,  Berlin,  1895;  and  Verworn,  Das  Neuron  in  Anat. 
und  Physiol.,  Jena,  1900  and  Med.  KHnik,  1908. 

2  Die  Neuronenlehre  und  ihre  Anhanger,  Jena,  1903. 

3  Allg.  Anat.  und  Physiol,  d.  Nervensystemes,  Leipzig,  1903. 
^  Mitt,  der  Zool.  Station  zu  Neapel,  xii,  1897. 

^  Wiirzburger  Abhandl.,  ii,   1902. 
*  Pfliiger's  Archiv,  cxii,  1906. 


566 


SIGNIFICANCE    OF   THE    NERVOUS    SYSTEM 


as  the  axons,  but  naturall}',  without  becoming  confluent  or  losing 
their  functional  independence.  In  other  places,  they  cross  and  give 
rise  to  by-stations  upon  the  general  conducting  path  which  is  amplified 
by  the  deposition  of  cytoplasm  and  nuclear  material.  Very  clearly, 
however,  the  fibrillar  concept  lays  emphasis  upon  the  conducting 
element  and  attaches  little  importance  to  the  cell-body. 


Fig.  281.  Fig.  282. 

Fig.  281. — Cell  from  the  Anterior  Horn  of  the  Spinal  Cord  of  Man,  Showing 
Xeurofibrils. 

ax.  Axon;  lil,  spaces  occupied  by  tigroid  material;  x,   fibrillar  connections  between 
neighboring  dendrites.      (Bethe.) 

Fig.  282. — Schematic  Representation  of  the   Neurofibrillar  Connections  in  a 
Pyramidal  Cell  of  the  Cerebral  Cortex.     (Cajal.) 

The  fibrillar  hypothesis  is  based  upon  structural  and  functional 
evidence.  Thus,  it  was  found  that  the  large  ganglion  cells  frequently 
display  an  intricate  network  such  as  is  shown  in  Fig.  282.  This  net- 
work was  assumed  to  represent  an  intracellular  ramification  of  fibrillse, 
Bethe,  moreover,  has  shown  that  in  young  animals  the  degenerating 
peripheral  ends  of  nerve  fibers  may  regenerate  without  first  having 


AKHANGEMKNT    OF    THE    NERVOUS    SYSTEM  567 

become  conncctiMl  with  their  cell-bodies.  It  has  also  been  proved  by 
this  investigator  Ihat  the  eell-body  is  not  essential  to  conduction. 
This  has  been  demonstrated  in  C-arcinus  maenas  in  which  the  nerve; 
of  the  second  antenna  is  composed  of  centrifugal  and  centripetal 
fibers  and  connects  with  a  ganglion  the  cell-bodies  of  which  are  situated 
somewhat  apart  from  the  fiber  network  or  neuropil.  On  removing 
the  former,  it  was  found  that  the  antenna  regained  its  former  tonus 
very  rapidly  and  that  its  stimulation  gave  rise  to  reflex  actions.  Ob- 
viously, in  this  case  conduction  is  had  even  in  the  absence  of  the 
cell-bodies  by  means  of  the  fibrillar  network  or  neuropil.  Steinach^ 
has  shown  that  this  condition  may  Ix;  duplicated  by  causing  the  cell- 
bodies  of  the  dorsal  root  ganglion  to  degenerate  or  by  removing  this 
ganglion  in  its  entirety.  Curiously  enough,  the  sensory  impulses 
continue  to  pour  into  the  spinal  cord  even  in  the  absence  of  this  gan- 
glion, and  hence,  it  may  be  inferred  that  they  reach  the  central  end  of 
the  posterior  root  without  being  required  to  make  station  at  this  point. 

Arguments  in  Favor  of  the  Neuron  Doctrine. — Regarded  in  a  very 
general  way,  it  may  be  said  that  nervous  processes  are  of  two  kinds: 
namely,  generative  or  central  and  conductile  or  peripheral.  The 
former  include  the  automatic  production  of  impulses  and  psychic 
activities  such  as  volition,  thought,  perception,  and  others.  The 
latter,  on  the  other  hand,  merely  represent  the  phenomena  of  conduc- 
tion accompanj'ing  the  passage  of  an  impulse  through  an  axon.  In 
perfect  harmony  with  this  functional  division,  the  nervous  system 
presents  itself  as  gray  matter  and  white  matter;  the  former  constituting 
the  central  nuclei  and  centers  of  function,  and  the  latter  the  paths  of 
conduction  by  means  of  which  these  complexes  of  ganglion  cells  are  con- 
nected either  with  one  another  or  with  peripheral  effectors  and  recep- 
tors. Physiologically,  it  is  quite  impossible  to  attribute  the  genera- 
tion of  impulses  to  the  conducting  element  of  the  neuron,  the  fibrillae. 
In  other  words,  creative  processes  can  only  be  referred  to  the  constitu- 
ents of  the  gray  matter,  the  cell-bodies.  Thus,  the  different  phenom- 
ena of  consciousness,  the  automatic  activity  of  the  centers,  and  other 
processes,  can  only  be  produced  by  the  cellular  units  of  the  gray  matter 
and  not  by  the  fibers  alone,  and  hence,  the  liberation  of  nervous 
energy  is  distinctly  a  duty  of  the  cells. 

A  similar  conclusion  must  be  drawn  from  the  time  relationship 
between  impulses  traversing  nerve  fibers  and  impulses  passing  through 
nuclei  and  centers.  It  is  a  well-established  fact  that  their  journey 
through  nerve  fibers  requires  a  much  shorter  time  than  their  passage 
through  centers.  The  deduction  to  be  derived  from  this  is  that  the 
ganglion  cells  possess  a  specific  activity  which  directly  affects  the 
nature  of  the  impulse. 

Looked  at  from  the  standpoint  of  embryology,  the  fibrillar  concept 
fails  to  establish  a  structural  unit,  because  the  axis  cylinders  of  the 
nerve  fibers  do  not  arise  from  outgrowths  of  the  cell-bodies,  but  from 
1  Pfliiger's  Archiv,  cxxv,  1908,  239. 


568  SIGNIFICANCE    OF   THE    NERVOUS   SYSTEM 

individual  local  cells  which  eventually  coalesce  to  form  the  conducting 
path.  In  accordance  with  the  neuron  concept,  the  different  neuro- 
blasts finally  elongate  and  form  their  own  axons.  These  changes  may 
be  traced  without  difficulty  in  neurons  which  are  made  to  grow  out- 
side the  body  in  a  medium  of  lymph. 

The  histological  evidence  favors  the  neuron  doctrine  in  a  very 
decisive  manner.  In  the  first  place,  it  has  been  proved  that  the 
"neurofibrillar"  network  found  in  the  immediate  vicinity  of  ganglion 
cells  (Bethe),  is  not  composed  of  fibrilljE  at  all,  but  constitutes  an  intri- 
cate system  of  lymphatic  channels  set  aside  for  the  nutrition  of  the 
cell-body.  In  this  connection,  reference  should  also  be  made  to  the 
fact  that  complexes  of  ganglion  cells  are  always  well  supplied  with 
blood-vessels  and  lymphatics,  while  nerve  fibers  are  not  (KoUicker). 
In  addition,  it  should  be  mentioned  that  some  ganglion  cells  are  in 
possession  of  an  internal  system  of  capillaries.  A  condition  of  this 
kind  exists  in  the  cells  of  the  medulla  of  Lophius  picatorius.  Further- 
more, the  cytoplasm  of  some  nerve  cells  contains  a  hemoglobin-like 
pigment,  a  fact  which  suggests  an  intense  metabolism.^ 

The  neuron  doctrine  also  receives  support  from  certain  data 
pertaining  to  the  metabolism  of  the  nerve  cell.  Thus,  it  has  been 
found  by  Langendorff-  that  the  gray  matter  readily  assumes  an  acid 
reaction  upon  activity  and  also  becomes  acid  after  death.  In  analogy 
with  the  changes  occurring  in  active  muscle,  it  has  been  assumed  that 
this  acidity  is  due  to  the  production  of  lactic  acid.  It  has  also  been 
stated  by  Mosso^  that  increased  mental  activity  is  associated  with  a 
rise  in  the  temperature  of  the  brain.  Reference  should  also  be  made 
at  this  time  to  the  fact  that  a  nei-ve  fiber  atrophies  when  separated 
from  its  cell-body,  and  that  ganglion  cells  display  very  obvious  histo- 
logical changes  during  growth  or  when  fatigued.  Since  a  more  de- 
tailed account  of  these  trophic  changes  will  be  given  in  a  subsequent 
paragraph,  attention  need  only  be  called  at  this  time  to  the  fact  that, 
unlike  the  cell-bodies,  the  nerve  fibers  cannot  be  fatigued  under  ordi- 
nary conditions  and  do  not  betray  an  intense  metabohsm.  This  fact 
implies  that  the  refractory  period  of  the  nerve  fiber  is  shorter  than 
that  of  the  nerve  cell.  Naturally,  the  only  deduction  to  be  derived 
from  these  data  is  that  the  ganglion  cells  are  the  more  active  nervous 
units  and  that  they  serve  as  the  generator  or  supply  house  of  nerve 
impulses. 

Fatigue  of  Nerve  Cells. — The  development  of  the  neuroblast  into 
its  mature  form  manifests  itself  by  a  deposition  of  additional  cellular 
material,  an  increase  in  the  number  of  its  processes,  an  acquisition  of 
enveloping  membranes  and  a  formation  of  pigment  granules  within 
the   cytoplasm.*     During   their   mature   state,   the  neurons  become 

1  Fritsch,  Archiv  ftir  mikr.  Anatomie,  xxvii,  1886,  13;  Holmgren,  Anat.  Hefte, 
XV,  1899,  and  Pewsner-Neufeld,  Anat.  Anzeiger,  xxiii,  1903. 
^  Zentralbl.  der  med.  WLssensch.,  1886. 
'  Die  Temperatur  des  Gehirnes,  1894. 
*  Vas,  Arch,  fur  mikr.  Anatomie,  1892. 


ARRANGEMENT  OF  THE  NERVOUS  SYSTEM 


oG9 


subject  to  structural  variations  in  consequence  of  changes  in  the  bodily- 
activities.  In  old  age,  certain  retrogressive  alterations  appear  which 
present  themselves  in  the  main  as  a  reversal  of  the  processes  observed 
during  the  growth  of  the  cell.  The  cytoplasm  decreases  in  volume, 
the  nucleus  becomes  smaller,  the  pigment  increases  and  the  different 
processes  decrease  in  number  and  mass.  In  fact,  in  some  cases  vacu- 
oles develop  which  finally  lead  to  the  complete  disappearance  of  the 
cell. 

A  most  interesting  picture  is  presented  by  nerve  cells  which  have 
been  fatigued.  Hodge,'  Mann-  and  Lugaro'  state  that  a  nonnal 
neuron,  when  stimulated,  first  increases  in  size,  because  its  motal)olism 
is  augmented  thereby.  Excessive  activity,  however,  diminishes  the 
amount  of  its  cytoplasm  as  well  as  that  of  its  nucleus  until  the  chro- 


FiG.  283. — Spinal  Ganglion   Cells   from   English   Sparrows,   to  Show  the  Daily 
Variation  in  the  Appearance  of  the  Cells  Caused  by  NoraL\L  Activity. 
A,  Appearance  of  cells  at  the  end  of  an  active  day;  B,  appearance  of  cells  in  the  morn- 
ing after  a  night's  rest.     The  cytoplasm  is  filled  with  clear,  lenticular  masses,  which  are 
much  more  evident  in  the  rested  cells  than  in  those  fatigued.     {Hodge.) 


matic  substance  has  been  used  up  in  its  entirety.  The  Nissl's 
granules  gradually  lose  their  conspicuousness  and  finally  disappear 
altogether.  If  long  continued,  the  exhaustion  of  the  reserve  supply 
of  energj'-yielding  material  manifests  itself  in  a  vacuolization  of  the 
cytoplasm  and  a  degree  of  disintegration  from  which  the  cell  cannot 
recover.  But  if  the  fatigue  is  not  carried  bej'-ond  a  certain  normal 
limit,  the  chromophil  substance  is  replenished  in  time.  Very  similar 
changes  have  been  observed  in  the  ganglion  cells  of  birds  after  long 
continued  flight,  for  example,  in  the  anterior  horn  cells  of  the  sparrow 
and  in  the  antennary  lobes  of  bees  at  the  end  of  an  active  day.     These 

1  Jour,  of  Morphology,  vii,  1892.  95. 

2  Jour,  of  Anat.  and  Physiol.,  xxLx,  1894.  100. 
*Lo  sperim.  giornale  medico.  Biol.,  F2,  1895. 


570 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


changes  belong  in  the  same  category  as  those  following  the  separa- 
tion of  the  cell-bodies  from  their  axons,  when  the  central  stump  and 
adjoining  cell-bodies  undergo  retrogressive  degenerative  alterations. 
We  then  obtain  a  turgcscence  of  the  cells  which  is  superseded  by 
atrophic  changes  and  chromatolysis. 

The  fact  that  the  gray  substance  of  the  centers  has  a  definite  meta- 
bolic requirement,  is  also  shown  by  the  grave  symptoms  which  follow 
almost  immediately  upon  the  occlusion  of  the  carotid  arteries  or  upon 
obstructions  to  arteries  which  supply  individual  centers  of  the  cere- 
brum. A  functional  uselessness  of  those  ganglion  cells  then  results 
which  are  situated  distally  to  the  block.     This  uselessness  is  evinced 

either  by  a  loss  of  motion  or  sensa- 
tion,  or  both.     A    similar    condition 
IH\  '"A  may  be  set  up  very  quickly  in  rabbits 

iyi\  'i'.\  by  compressing  the  abdominal  aorta 

"'  '^  ^  (Stenson's  experiment).     The  anemia 

of  the  spinal  centers  resulting  from 
this  obstruction,  soon  leads  to  a  pa- 
ralysis of  the  posterior  extremities  and, 
peculiarly  enough,  the  motor  paraly- 
sis precedes  the  loss  of  sensation  (anes- 
thesia). This  dissociation  suggests  a 
difference  in  the  resistance  of  different 
nervous  elements  to  anemia. 

Verworn^  states  that  the  fatigue 
of  nerve  cells  may  be  brought  about 
in  two  ways,  namely,  by  causing  an 
accumulation  of  the  waste-products  or 
by  exhausting  the  reserve  nutritive 
material  of  the  cell.  The  former  in- 
duces fatigue  and  the  latter,  the  more 
serious  condition  of  exhaustion.  The 
experiments  which  are  directly  con- 
cerned with  the  metabolism  of  nerve 
centers,  consisted  in  perfusing  the 
central  nervous  system  through  the  aorta  with  defibrinated  blood  and 
saline  solution  containing  varying  amounts  of  oxygen.  Thus,  if  the 
blood  of  a  frog  poisoned  with  strychnin,  was  slowly  displaced  by  saline 
solution  free  from  oxygen,  the  muscular  spasms  gradually  became  less 
violent  and  finally  disappeared  altogether.  The  subsequent  perfusion 
with  thoroughly  aerated  defibrinated  blood,  however,  soon  caused 
these  spasms  to  reappear  with  renewed  intensity.  The  same  results 
were  obtained  with  saline  solution  fully  charged  with  oxygen,  while 
blood  serum  free  from  oxygen,  prevented  the  recurrence  of  the  spasms. 
This  observation  proves  very  conclusively  that  the  recuperation  is  not 
dependent  upon  the  organic  substances,  but  rather  upon  the  oxygen; 
1  Arch,  fur  Anat.  und  Physiol.,  1900,  385. 


Fig.  284. — Two  Motor  Cells 
•  FROM  THE  Lumbar  Cord  of  a  Dog. 
A,  From  rested,  and  B,  from 
fatigued  dog;  showing  the  diminu- 
tion in  the  size  of  the  cell,  the  changes 
in  the  size  and  shape  of  the  nucleus 
and  the  chromatolysis.  (After 
Mann.) 


ARRANGEMENT    OF    THE    NERVOUS    SYSTEM  571 

moreover,  subsequent  experiments  hiivo  shown  that  the  activity  of 
the  ganghon  cells  varies  directly  with  the  quantity  of  oxygen  supplied 
to  them.     Hence,  their  power  of  oxidation  can  no  longer  be  doubted. 

It  has  been  established  that  prolonged  muscular  exercise  gives 
rise  to  fatigue  substances,  consisting  of  carbon  dioxid,  lactic  acid  and 
monopotassium  ])hosphate.^  In  analogy  with  this  observation, Dol- 
ley-  recognizes  a  "fatigue  of  depression"  throughout  the  body,  which 
results  in  consequence  of  the  production  of  toxic  substances,  and  a 
"fatigue  of  excitation"  which  follows  the  excessive  consumption  of 
nervous  material.  Thus,  it  is  a  common  experience  that  excessive 
muscular  fatigue  reduces  our  mental  efficiency,  while  conversc.'ly, 
mental  fatigue  weakens  our  muscular  power  and  other  bodily  functions. 
It  is  argued  further  that  the  highly  organized  centers  are  more  suscep- 
tible to  fatigue  than  the  ordinary  reflex  centers,  because  mental  work 
produces  symptoms  of  fatigue  with  much  greater  ease  than  muscular 
exercise.  This  is  especially  true  of  young  children  who  "go  stale" 
very  quickly  unless  their  mental  training  is  properly  balanced  by  rest 
and  play.  But  while  we  may  feel  justified  in  assuming  that  ganglion 
cells  give  rise  to  fatigue  substances,  we  have  not  succeeded  as  yet  in 
isolating  these  bodies,  the  only  possible  exception  being  carbon  dioxid. 
Winterstein^  has  shown  that  the  administration  of  this  gas  produces 
an  exhaustion  of  the  nerve  cells  within  a  very  short  time. 

The  Refractory  Period  of  the  Nerve  Cell. — It  will  be  recalled  that 
cardiac  muscle  is  impervious  to  stimuli  during  systole  but  gradually 
becomes  more  irritable  as  the  end  of  the  diastolic  period  is  reached.'* 
Systole  is  the  period  during  which  the  contractile  substance  is  used  up, 
and  diastole  the  period  during  which  it  is  again  acquired.  This 
type  of  protoplasm,  therefore,  is  not  in  a  condition  to  receive  stimuli 
so  long  as  those  internal  reactions  are  being  promulgated  which  give 
rise  to  its  contraction.  It  again  becomes  receptive  during  its  recuper- 
ative period,  i.e.,  during  the  diastole  and  pause.  In  a  similar  way,  it 
is  held  that  nerve  tissue  undergoes  cataboHc  and  anabolib  changes, 
and  hence,  a  sufficient  time  must  always  be  allowed  to  elapse  between 
two  successive  stimuli,  otherwise  the  material  will  not  be  at  hand  with 
which  to  produce  the  subsequent  reaction.  Thus,  if  the  successive 
stimuli  are  sent  into  nerve  tissue  with  an  increasing  rapidity,  a  point 
will  eventually  be  reached  when  no  reaction  can  result.  The  stimuli 
then  become  ineffective,  because  not  enough  time  has  been  allowed 
for  the  renewal  of  that  material  which  has  been  used  up  during  the 

1  The  formation  of  the  so-called  muscle  toxins  has  been  denied  by  Lee  (Proc. 
Soc.  Exp.  Med.  and  Biology,  1917). 

2  Intern.  Monatsschrift  fiir  Anat.  und  Physiol.,  xxxi,  1914,  35. 

3  Zeitschr.  fiir  allg.  Physiol.,  vi,  1906,  315. 

*  Discovered  by  Marey,  (Compt.  rend.,  1891)  and  applied  to  nerve  tissue  by 
Broca  and  Richet  (Compt.  rend.,  1897).  These  investigators  found  that  the 
cortical  cells  are  unirritable  for  some  time  after  the  cessation  of  the  muscular 
spasms,  such  as  occur  in  chorea  and  epilepsy. 


572  SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 

preceding  period  of  activity.  This  interval  during  which  the  irrita- 
bihty  is  at  low  ebb,  constitutes  the  refractory  period. 

In  the  case  of  nerve  fibers,  the  period  of  refraction  is  extremely 
brief,  in  spite  of  the  fact  that  they  undergo  metabolic  changes.  It 
amounts  to  only  0.002-0.006  sec.  Their  extremely  rapid  power  of 
recuperation  is  dependent  upon  their  great  affinity  for  oxygen.  It  is 
possible,  however,  to  render  this  period  more  evident  by  lessening  the 
amount  of  the  availal)le  oxygen  which  can  be  done  most  easily  b}^  sur- 
rounding the  nerve  fiber  with  some  inert  gas  or  narcotizing  agent.  ^ 
Cell-bodies  behave  very  similarly,  but  as  their  metabolic  requirements 
are  much  greater  than  those  of  the  nerve  fibers,  their  refractory  period 
is  also  more  clearly  marked.  Thus,  it  has  been  found  that  a  refrac- 
tory period  of  0.006  sec.  for  the  nerve  fibers  of  the  frog  corresponds  to 
a  refractory  period  of  0.1  sec.  for  the  ganglion  cells  of  the  same  animal. 
This  time  may  be  varied  by  altering  the  irritability  of  the  cell,  either  by 
lessening  the  amount  of  the  available  oxygen  or  by  narcosis. 

As  the  cell-bodies  of  different  groups  of  neurons  are  destined  to 
perform  different  functions,  it  may  be  conjectured  that  their  anabolic 
requirements  are  subject  to  considerable  variations.  Hence,  although 
their  refractory  period  is  much  longer  than  that  of  the  nerve  fiber,  the 
value  of  0.1  sec.  must  vary  somewhat  in  accordance  with  the  type 
of  cell  under  consideration.  It  has  also  been  suggested  that  the 
refractory  period  acts  as  a  check  upon  those  impulses  which  ganglion 
cells  discharge  automatically.  It  is  a  well-known  fact  that  the  dif- 
ferent motor  organs,  such  as  muscle  tissue  and  glandular  tissue,  are 
constantly  kept  in  a  condition  of  tonus  in  consequence  of  an  outpouring 
of  subminimal  impulses  by  their  respective  centers.  These  impulses 
are  said  to  be  generated  at  the  rate  of  about  10  in  a  second.  Obvi- 
ously, as  the  refractory  period  amounts  to  0.1  sec,  they  could  not 
be .  repeated  at  shorter  intervals.  Nor  could  they  recur  at  longer 
intervals,  because  the  excessive  rise  in  irritabilitj^  would  eventually 
cause  them  to  be  discharged  irrespective  of  any  stimulation.  It  is 
believed  that  some  ganglion  cells  discharge  their  impulses  even  more 
rapidly  than  10  in  a  second,  namely,  40-100  in  a  second,  but  a  mere 
difference  in  rate  does  not  destroy  the  principle  involved  in  this 
process  of  self-regulation,  because  the  refractory  period  must  neces- 
sarily become  the  shorter,  the  greater  the  rate  of  discharge.  At  no 
time,  however,  could  it  equal  the  refractory  period  of  nerve  fibers. 

Summation  of  Stimuli  in  Nerve  Cells. — The  phenomenon  of  sum- 
mation is  well  illustrated  by  the  summation  of  the  contractions  of 
skeletal  muscle.  If  a  number  of  stimuli  of  the  same  intensity  arc 
passed  into  muscle  tissue  at  brief  intervals,  the  resulting  contractions 
are  added  to  one  another  until  the  total  reaction  displays  a  very  much 
greater  amplitude  than  that  of  the  single  contractions.  A  strength  of 
stimulus  may  also  be  employed  which  does  not  give  rise  to  a  reaction, 
while  two  or  three  stimuh  of  this  intensity  applied  in  rapid  succession, 
1  Frohlich,  Zeitschr.  fiir  allg.  Physiol.,  iii,  1904,  148. 


ARllANC.EMENT    OF    THE    NERVOITS    SYSTEM  573 

produco  a  roacfion.  This  pluMioiiuMion  constitutes  the  summation  of 
subminimal  stimuli.  It  should  \)v  remcmlxM-od,  however,  that  we  ar(> 
not  dealing  in  this  case  with  a  storage  or  ordinary  addition  of  individual 
stimuli,  but  with  a  state  of  increased  sensitiveness  of  the  living  sub- 
stance. In  other  words,  the  first  stimulus,  although  subminimal 
in  character,  gives  rise  to  certain  changes  in  the  (rell  which  render 
it  more  susceptible  to  the  succeeding  stimulus.  This  is  really  a  general 
experience,  because  certain  reactions  may  be  elicited  with  much  greater 
promptness  by  a  succession  of  moderate  stimuli  than  by  a  single 
stimulus  of  great  intensity.  This  is  especially  true  of  the  stimulation 
of  the  cerebral  cortex  and  other  complexes  of  nerve  cells  mediating 
reflex  actions. 

Setschenow^  has  proved  that  nerve  fibers  and  ganglion  cells  behave 
very  differently  toward  stimidi.  Thus,  it  is  conceded  that  the  state 
of  excitation  in  nerve  fibers  does  not  outlast  the  stimulus  for  any  con- 
siderable length  of  time,  while  nerve  cells  retain  a  state  of  greater 
irritability  even  after  slight  stimuli  and  show,  therefore,  a  greater 
responsiveness  to  succeeding  stimuli.  We  make  use  of  this  fact  in  a 
practical  way  in  eliciting  reactions  in  the  realm  of  the  sympathetic 
system  and  in  testing  the  different  reflexes  for  purposes  of  diagnosis. 
Thus,  a  number  of  light  taps  upon  the  patellar  ligament  often  result 
in  a  positive  reaction  when  a  single  strong  one  does  not.  It  has  also 
been  observed  that  long-continued  pressure  is  at  times  more  effective 
than  a  single  mechanical  stimulus  of  much  greater  intensity.  The 
same  is  true  of  the  stimuli  ehcited  by  stroking  the  surface  of  the  body 
(tickling)  and  of  the  light,  sound  and  chemical  impacts  imparted 
respectively  to  our  retinae,  organs  of  Corti,  taste-buds  and  olfactory 
cells. 

Facilitation  or  "Bahnung." — Most  closely  allied  to  this  phenom- 
enon is  the  so-called  stair-case  contraction  or  "Treppe"  of  striated 
and  cardiac  muscle  tissue.  It  will  be  remembered  that  if  these  tissues 
are  rendered  more  sensitive  either  by  exposing  them  to  subminimal 
stimuh  or  by  the  administration  of  fatigue  substances,  their  contrac- 
tions gradually  increase  and  remain  large  until  this  state  of  hyper- 
susceptibility  has  been  terminated.  It  should  be  noticed,  therefore, 
that  the  "Treppe"  is  not  caused  by  an  increased  intensity  of  stimula- 
tion but  by  an  augmentation  of  the  contractile  power  of  the  muscle 
substance.  A  similar  change  takes  place  in  nerve  tissue  when  made  to 
perform  the  same  task  a  number  of  times  in  succession.  An  impulse 
which  is  made  to  pass  through  a  certain  set  of  neurons  a  great  many 
times,  gradually  breaks  down  the  resistance  in  this  path  so  that  the 
latter  becomes  more  particularly  adapted  to  it.  This  ''Bahnung" 
is  largely  a  matter  of  the  cell-bodies,^  because,  as  we  have  just  seen, 
the  resistance  in  the  centers  is  infinitely  greater  than  that  met  with 

^  tlber  die  elektr.  Reizung  der  sens.  Riickenmarksnerven  des  Frosches,  Graz, 
1868;  also:  Biedermann,  Pfliiger's  Archiv,  Ixxx,  1900,  451. 
-  Exner,  Pfluger's  Archiv,  xxviii,  1882,  487. 


574  SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 

along  the  fiber  path.  The  repetition  of  impulses,  therefore,  leads  to 
the  formation  of  open  paths,  and  herein  lies  the  cause  of  facilitation 
which  in  turn  gives  rise  to  the  formation  of  habits  constituting  the 
neural  basis  of  memory. 

Inhibition. — It  must  be  clear  that  afferent  impulses  can  produce 
their  characteristic  reactions  only  if  the  neurons  over  which  they 
pass,  do  not  simultaneously  conduct  other  impulses.  Stated  differ- 
ently, the  primary  impulse  must  have  a  perfectly  clear  path  before  it, 
otherwise  a  conflict  will  arise  between  them  which  must  finally  lead 
to  the  obliteration  of  one  or  the  other  of  these  impulses.  Only  the 
more  effective  of  them  will  succeed  in  eliciting  a  reaction.  It  is  com- 
monly believed  that  this  inhibition  and  elimination  of  impulses  occurs 
in  the  centers  and  not  in  the  fiber  paths,  because  the  function  of  the 
central  cells  consumes  time  and  energy  so  that  they  cannot  do  more 
than  attend  to  a  single  activity. 

Inhibitory  phenomena  are  explained  in  two  ways,  namely,  by  as- 
suming a  paralysis  of  the  assimilative^  or  a  paralysis  of  the  dissimila- 
tive  processes.  In  accordance  with  the  latter  hypothesis,  which  seems 
to  be  the  more  acceptable,  all  nervous  processes  are  considered  as 
excitations  of  dissimilative  changes  and  hence,  inhibitions  must 
result  whenever  this  dissimilation  following  upon  the  reception  of  an 
impulse,  is  stopped.  Clearly,  therefore,  the  chief  factor  in  inhibition 
seems  to  be  an  attenuation  of  the  refractory  condition  of  the  nerve 
cell  towards  secondary  impulses.  ^ 


CHAPTER  XL VII 
THE  FUNCTIONAL  UNIT  OF  THE  NERVOUS  SYSTEM 

The  Reflex  Concept. — In  the  same  manner  as  the  complex  masses 
of  nervous  tissue  may  be  reduced  to  a  single  unit,  designated  as  the 
neuron,  so  may  all  nervous  actions  be  reduced  to  a  simple  action, 
known  as  a  reflex.  In  the  same  way  as  the  neuron  forms  the  build- 
ing stone  of  the  nervous  system,  so  does  the  reflex  constitute  the  func- 
tional basis  of  all  nervous  processes.  To  be  sure,  there  are  many 
organisms  in  existence  which  are  not  in  possession  of  a  nervous  system 
nor  even  of  nervous  elements,  but  which  nevertheless  react  in  a  manner 
that,  relatively  speaking,  cannot  be  said  to  be  inferior  to  the  power 
of  reaction  of  the  higher  forms.  But  as  these  forms  are  absolutely 
devoid  of  nervous  tissue,  their  "actions  cannot  be  said  to  be  reflex  in 

^  Gaskell,  Jour,  of  Phvsiol.,  vii,  1885;  also:  Meltzer,  New  York  Med.  Jour., 
1899. 

2  Verworn,  Archiv  fiir  Physiol.,  Suppl.,  1900,  and  Zeitschr.  fur  allg.  Physiol., 
vi,  1907. 


THE    FUNCTIONAL    UNIT    OF    THE    NERVOUS    SYSTEM  oTo 

their  nature.  If  an  ameba  retracts  its  pscudopodia  or  if  a  iliizopod 
sends  out  its  protoplasmic  filaments  into  th(^  surrounding  medium, 
stimulations  of  some  sort  must  have  taken  jjlace  directly  precedinji; 
these  responses.  But  as  these  excitations  have  resulted  in  livinfr 
substance  which  is  free  from  nervous  elements,  the  reactions,  although 
just  as  complex  as  many  of  those  exhibited  by  the  higher  animals,  can 
only  be  said  to  be  refiex-like  in  their  character. 

The  other  group  of  organisms,  embracing  those  possessing  nervous 
elements,  shows  a  gradually  increasing  complexity  in  the  arrangement 
of  its  nervous  units  and  also  a  steadily  increasing  complexity  in  its 
reactions.  The  simplest  of  these  are  designated  as  reflexes  and  the 
most  complex,  as  associated  actions  or  voluntary  reactions.  The  divid- 
ing line  between  these  processes  Ues  in  volition.  Thus,  we  may  use 
the  term  reaction  in  a  very  general  way  as  designating  any  response 
to  a  stimulus,  but,  more  correctly  speaking,  it  should  be  restricted 
to  that  response  which  is  accomplished  with  the  aid  of  the  will.  A 
reaction,  therefore,  is  a  volitional  action,  while  a  reflex  is  an  action 
which  is  not  influenced  by  volition.  To  summarize,  the  different 
actions  shown  by  animals  may  be  divided  into  reflex-like  actions, 
reflexes  and  complex  reactions.  The  first  of  these  are  had  solely  with 
the  aid  of  ordinary  protoplasm,  while  the  last  two  necessitate  the  pres- 
ence of  that  differentiated  type  of  living  substance  which  we  call 
neuroplasm.  Furthermore,  as  long  as  an  action  of  the  latter  kind  is 
not  influenced  by  the  will,  it  remains  a  reflex,  but  becomes  a  complex 
reaction  immediately  upon  the  entrance  of  volition. 

The  Reflex  Circuit. — It  need  scarcely  be  emphasized  that  the  pres- 
ent discussion  must  be  restricted  very  largely  to  the  analysis  of  the 
nervous  activities  of  the  higher  forms  and  hence,  reflex-like  actions 
must  be  left  for  later  consideration.  The  phenomena  of  life  have  been 
divided  into  spontaneous  manifestations  and  manifestations  of  stimu- 
lation. Strictly  speaking,  however,  this  classification  is  incorrect, 
because  life  consists  in  a  reaction  of  living  substance  to  outside  in- 
fluences. Hence,  stimulations  are  always  present  and  a  state  of  abso- 
lute spontaneity  cannot  arise.  Stimuli  are  constantly  brought  to 
bear  upon  organisms  and  it  is  their  destiny  to  react  toward  them  in 
accordance  with  their  structural  and  functional  equipment.  Moreover, 
if  we  define  a  stimulus  as  any  extraordinary  alteration  in  the  conditions 
which  nature  has  imposed  upon  us,  we  must  immediately  be  struck 
by  the  enormous  diversity  of  influences  to  which  we  may  be  subjected. 
Animals,  very  naturally,  react  toward  these  changes  in  harmony 
with  the  development  of  their  nervous  system.  The  lower  forms  being 
constructed  along  much  simpler  lines,  are  essentially  reflex  animals, 
for  the  reason  that  their  psychic  activities  are  lacking  and  their  actions 
cannot,  therefore,  be  dominated  by  the  will.  The  higher  animals, 
on  the  other  hand,  are  reaction-animals,  because  their  psychic  life 
absolutely  controls  their  simple  reflex  functions. 

A  reflex  is  a  response  to  a  stimulus  executed  without  the  interven- 


576 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


tion  of  the  will.  This  definition  implies  that  the  impulse  generated 
in  the  sense-organ,  must  be  conveyed  to  a  center  before  it  can  be 
transferred  to  the  corresponding  motor  end-organ  (Fig.  285).  In 
its  simplest  form,  therefore,  the  nervous  circuit  which  is  necessary 
for  the  mediation  of  a  reflex,  must  consist  of  two  neurons,  one  of  which 
serves  the  purpose  of  conveying  the  impulse  from  the  sense-organ  (R) 
to  the  center,  and  the  other,  from  the  center  (C)  to  the  motor  organ 
(Er).  The  first  neuron  forms  the  sensory  path  {A)  and  the  second, 
the  motor  path  (E)  of  this  reflex  arc  or  circuit.  The  terms  afferent  and 
centripetal  are  frequently  applied  to  the  ingoing  path  and  the  terms 
efferent  and  centrifugal  to  the  outgoing  path.     Furthermore,  the  sen- 


FiG.  285.  Fig.  286. 

Fig.  285. — Diagram  Illustrating  the  Construction  of  the  Reflex  Circuit. 
72,  Receptor;  A,  sensory  path;  C,  center;  E,  motor  path;  Er,  effector. 

Fig.  286. — Diagr.^m    Illustrating   the    Construction  of  the   Reaction   Circuit 
(Volitional  Response). 

R,    Receptor;    A,  primary  sensory  path;   C,   reflex  center;   A',  secondary   sensory 
path;  V,  higher  center;  E',  primary  motor  path;  E,  secondary  motor  path,  Er,  effector. 


sory  side  of  the  reflex  arc  is  often  designated  as  the  analyzer,  while  the 
sensory  end-organ  is  called  the  receptor  and  the  motor  end-organ  the 
effector.  Stated  in  detail,  therefore,  a  reflex  circuit  is  composed  of  a 
receptor,  a  sensory  path,  a  center,  a  motor  path  and  an  effector. 

The  circuit  required  for  a  volitional  reaction,  differs  from  the  reflex 
circuit  only  in  the  number  of  neurons  which  are  necessary  to  convey 
the  impulse  into  the  cerebrum  where  the  psychic  faculties  (volition) 
are  situated.  The  impulse  is  first  conveyed  from  the  receptor  to  the 
lower  (reflex)  center  and  from  here  by  a  secondary  afferent  neuron 
to  the  higher  center  involving  volition.  Upon  its  being  transferred 
to  the  efferent  side  of  the  reaction  arc,  the  impulse  first  attains  the 
lower  center  and  later  on  the  effector. 

The  Rudimentary  Nervous  System  is  a  Reflex  System. — The  neuron, 
as  has  been  emphasized  above,  is  the  structural  unit  of  the  nervous 


THE    FUNCTIONAL    UNIT   OF   THE    NERVOUS   SYSTEM         577 

system.  Physiologically,  however,  the  neuron  attains  its  greatest 
importance  only  when  several  of  them  are  joined  to  form  reflex  circuits, 
because  only  then  do  we  obtain  the  structural  basis  for  the  reflcsx  act 
which  constitutes  the  functional  unit  of  the  nervous  system.  Obviously, 
if  an  electric  shock  is  passed  dirc^ctly  into  muscle  tissue,  it  r(;acts  by 
giving  a  contraction.  The  same  result  may  be  obtained  by  stimulat- 
ing^ the  nerve  innervating  this  muscle.  In  either  case,  it  is  to  be 
noted  that  this  action  does  not  const  itute  a  reflex,  because  it  is  accom- 
plished in  a  direct  manner  and  not  through  the  intervention  of  a  num- 
ber of  neurons  arranged  in  proper  series.  In  order  that  the  aforesaid 
muscular  contraction  may  become  a  true  reflex  response,  it  is  neces- 
sary to  bring  the  stimulus  to  bear  upon  some  afferent  nerve,  whence 
the  impulse  is  transferred  to  the  motor  nerve  of  this  muscle. 

Clearly,  the  cells  constituting  the  tissues  and  organs  of  the  higher 
forms,  behave  in  the  same  manner  as  unicellular  organisms.  They 
possess  irritability,  conductivity  and  contractility  and  hence,  give 
rise  to  motor  effects  whenever  stimulated.  If  a  vorticella  is  touched, 
an  excitation  results  which  is  conducted  to  the  myoids  situated  in  its 
stalk.  A  contraction  follows  which  causes  the  bell-shaped  upper 
portion  of  this  organism  to  be  retracted  from  the  seat  of  the  stimula- 
tion. In  a  similar  way,  an  electrical  shock  applied  to  a  muscle, 
gives  rise  to  a  wave  of  excitation  which  finally  leads  to  general  changes 
within  its  myoplasm.  The  function  of  the  nervous  system,  there- 
fore, is  not  to  impart  these  elementary  properties  to  organisms,  be- 
cause all  living  substance  is  irritable,  conductile  and  contractile. 
Its  real  object  is  to  insure  a  functional  correlation  between  the  different 
cellular  units  of  the  body,  so  that  the  latter  are  enabled  to  react  to 
changes  in  the  environment  as  one  single  coordinated  whole.  It  is 
also  true  that  nervous  tissue  is  peculiarly  suited  to  bring  this  coopera- 
tion about,  because  the  neuroplasm  of  which  it  is  composed,  possesses 
the  properties  of  irritability  and  conductivity  in  an  even  greater 
measure  than  ordinary  living  substance. 

A  general  survey  of  the  animal  kingdom  shows  that  the  forms  be- 
low the  coelenterata  do  not  possess  definite  nervous  structures. 
Their  life  processes,  as  far  as  we  know  at  the  present  time,  are  not 
correlated  by  cells  other  than  those  forming  their  tissues.  In  the 
coelenterata,  however,  certain  cells  are  found  which  are  particularly 
sensitive  and  appear  to  be  set  aside  for  the  singular  purpose  of  receiving 
stimuli  from  wdthout  and  of  transferring  the  resulting  impulses  to 
other  colonies  of  cells.  We  find  these  units  in  the  external  strata  of 
the  body,  i.e.,  in  the  epiblast  (Fig.  287,A).  Their  internal  poles  are 
drawn  out  into  slender  processes  which  eventually  invade  the  deeper 
layers  (Fig.  287,  B  and  C).  Here  they  are  brought  into  contact  with 
secondary  nervous  elements  which  finally  connect  with  the  underlying 
muscle  tissue  (Fig.  287,1)).  An  arrangement  of  this  kind,  representing 
really  the  lowest  type  of  nervous  system,  is  found  in  the  jelly-fish. 
The  sensory  cells  which  are  situated  in  among  the  external  lining  cells 

37 


578 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


of  the  umbrella,  lie  in  relation  with  a  more  deeply  placed  network  of 
fibers  in  which  a  number  of  nerve  cells  are  embedded.  Fibers  extend 
from  here  to  the  reactive  tissue  in  the  innermost  layers  of  the  umbrella, 
tentacles  and  manubrium.  It  appears,  therefore,  that  these  organisms 
are  already  in  possession  of  complete  reflex  circuits,  each  of  which  is 
composed  of  a  receptor,  a  sensory  path,  an  intervening  neuron 
forming  the  center,  and  an  efferent  path  with  its  effector.  In  fact, 
this  differentiation  of  the  nervous  elements  seems  to  have  progressed 
quite  far,  because  the  sensory  cells  show  certain  individual  differences 
which  lead  us  to  suspect  that  some  of  them  are  set  aside  for  the  recep- 
tion of  mechanical  impacts  and  rays  of  light,  while  others  seem  to  be 
concerned  with  the  position  of  the  organism  in  space  (static  sense). 


OiO    0     0 

I I I — L 

C 

0     •    0     o     o 


B 

1 

0    o 

1. 

v.. 

D 

0    0 

. 

0  1  0 

1  ! 

Fig.  287. — Diagram  Illustrating  the  Evolution  of  the  Nervous  System. 
A,  Ordinary  living  cells;  B,  processes  are  sent  out  by  some  of  them  which  (C)  con- 
nect with  similar  processes  of  more  deeply  placed  nerve  cells;  D,  the  latter  in  turn  form 
connections  with  the  muscle  cells,  thereby  completing  the  path  between  the  sensory  cell 
and  the  effector. 


It  is,  of  course,  quite  probable  that  a  more  rudimentary  arrangement 
than  this  will  in  time  be  discovered  in  other  forms;  so  far,  however, 
the  one  described  is  the  most  elementary  with  which  we  are  acquainted. 

The  Evolution  of  the  Reflex  System  into  a  Reaction  System. — While 
a  segmental  arrangement  of  the  tissues  and  organs  is  quite  apparent 
even  in  the  highest  animals,  this  condition  niay  be  studied  most 
advantageously  in  such  forms  as  the  vermes  and  crustacese.  The 
term  segmentaUsm  really  signifies  that  the  bodies  of  these  animals 
are  made  up  of  a  number  of  smaller  units  which  are  capable  of  leading 
an  independent  existence.  This  is  made  possible  by  the  fact  that  each 
segment  is  equipped  with  a  digestive,  excretory,  circulatory  and  nervous 
system,  so  that  a  structural  dissociation  may  be  effected  between 
them  without  destroying  or  seriously  impairing  their  life  processes. 

As  far  as  the  nervous  system  is  concerned,  we  find  that  the  different 
segments  (Fig.  288)  contain  a  centrally  placed  ganglion  (G)  from  which 


THE    FUNCTIONAL    UNIT    OF    THE    NERVOUS    SYSTEM 


579 


fibers  extend  in  all  directions  to  the  different  tissues  of  the  segment. 
A  stimulus  applied  to  its  surface  (S),  is  soon  followed  by  movements  or 
some  other  motor  response  (E),  and  hence,  we  must  conclude  that  the 
nervous  material  allotted  to  each  segment,  is  arranged  in  the  form 
of  reflex  arcs,  the  centers  of  which  are  situated  in  the  ganglion.  While 
a  high  degree  of  independency  is  thus  assured  to  each  segment,  it  must 
be  admitted  that  the  life  of  the  entire  animal  requires  in  addition  a 
proper  correlation  between  its  different 
parts.  The  functions  of  its  segments  must 
be  subordinated  to  the  requirements  of  the 
whole.  This  end  is  accomphshed  by  in- 
termediary neurons  (A)  which  unite  the 
successive  ganglia  with  one  another.  These 
association  fibers  are  placed  longitudinally 
to  the  long  axis  of  the  animal  and  form  in 
this  way  a  conducting  channel  akin  to  the 
spinal  cord  of  the  higher  forms.  It  is  also 
to  be  noted  that  the  head  ganglia  are  es- 
pecially well  developed  and  exercise  a  con- 
trolling influence  over  the  other  ganglia. 
Eventually  these  central  complexes  also 
become  the  recipients  of  impulses  from  cer- 
tain sense-organs,  such  as  the  eyes,  and  the 
receptors  for  chemical  and  vibratory  im- 
pacts. This  is  of  importance,  because  the 
movements  and  general  behavior  of  the 
animal  naturally  demand  a  proper  correla- 
tion of  all  these  different  sensory  impres- 
sions. It  should  be  emphasized,  however, 
that  those  animals  which  are  equipped 
with  a  nervous  system  of  this  kind,  are  not 
capable  of  forming  associations.  They  are, 
therefore,  true  reflex  animals  for  the  reason 
that  they  are  not  in  possession  of  those 
complexes  of  neurons  which  give  rise  to 
psychic  activities  (cerebrum). 


Fig.  288. — Diagrammatic 
Representation  of  the  Ner- 
vous System  of  a  Segmental 
Animal. 

G\  G2  and  G^  Ganglia  in 
three  successive  segments. 
S\  S^  and  S^  and  E\  E^  and 
E^,  the  receptors  and  effectors 
of  those  segments  forming  the 
end  stations  of  typical  reflex 
circuits;  A,  association  paths 
uniting  the  reflex  centers  of 
the  successive  segments. 


By  way  of  illustration,  let  us  devote  a  few 
moments  to  a  consideration  of  the  nervous  system 
of  the  crayfish  (Fig.  289).     It  consists  of  thirteen 

ganglia,  sL\  of  which  are  allotted  to  the  abdomen,  six  to  the  thorax  and  one  to  the 
head  region.  As  the  most  anterior  of  these  lies  in  close  relation  with  the  esophagus, 
it  is  usually  called  the  supra -esophageal  or  supramaxillary  ganglion  {A).  The  fibers 
emitted  by  every  one  of  these  ganglia,  are  distributed  to  the  muscles  and  the  sense- 
organs  of  the  integument.  They  are  brought  into  relation  with  those  of  the  opposite 
side  by  intermediate  neurons.  Connections  are  also  made  with  the  neighboring 
ganglia  by  means  of  commissural  fibers.  Each  ganglion,  therefore,  is  partially 
divided  into  two  lobes  and  this  bilateralism  is  also  apparent  in  the  path  connecting 
them.  The  first  thoracic  or  subesophageal  ganglion  (C)  is  more  highly  developed 
than  the  others,  because  it  forms  the  link  between  the  chain  of  posterior  ganglia 


580 


SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 


and  the  supra-esophageal  ganglion.  It  appears  to  be  made  up  of  several  and  sends 
out  two  commissures  (B)  which  encircle  the  esophagus  and  eventually  unite  with 
the  large  supra-esophageal  gangUon.  Besides,  it  gives  origin  to  ten  pairs  of  nerves 
which  innervate  the  mandibles,  the  maxillae,  and  the  maxillipedes  with  their 
branchial  appendages.  A  still  greater  differentiation  is  pre- 
sented by  the  head  ganglion  which  consists  of  three  pairs  of 
nodular  enlargements,  nameh',  the  protocerebron,  the  deutero- 
cerebron  and  the  tritocerebron.  The  optic  nerves  (O)  enter  the 
foremost  of  these,  while  the  middle  ones  receive  fibers  from  the 
integument,  antennse  and  organ  of  hearing  (R).  The  posterior 
nodules  give  origin  to  the  nerves  innervating  the  large  external 
antenna;  (D). 

An  arrangement  of  this  kind  constitutes  a  typical  reflex  stem, 
around  which,  in  the  higher  forms,  the  association  or  reaction 
system  is  developed.  The  greatest  change  is  eifected  anteriorly 
in  the  region  of  the  head  ganglia,  because  these  bodies  are  destined 
to  become  the  recipients  of  the  impulses  from  the  chief  sense 
organs.  Eventually,  many  of  these  impulses  are  not  permitted 
to  pass  directly  upon  efferent  channels,  but  are  first  conducted 
into  certain  complexes  of  nerve  cells  in  which  they  are  asso- 
"j^  ciated.     In  this  way,  each  sensory  reflex  area  is  finally  invested 

^Q"  by  a  sphere  of  association,  the  nervous  products  of  which  give 

^F"  rise  to  the  psychic  life  of  the  animal.     ThLs  development  of  the 

different  association  centers  takes  place  gradually.  The  first  to 
make  its  appearance  is  the  center  for  smell,  because  smell  is  the 
most  primitive  sense  and  many  animals,  such  as  the  amphibia 
and  reptilia,  depend  upon  it  almost  exclusively.  It  need 
scarcely  be  emphasized  that  the  development  of  these  associa- 
tion spheres  increases  the  complexity  of  the  nervous  system 
very  pronouncedly,  because  the  primitive  reflex  stem  is  now 
materially  augmented  by  the  addition  of  the  brain.  Quite  aside 
from  this  structural  and  functional  complexity  of  the  nervous 
system  of  the  higher  animal,  it  should  be  noted  especially  that 
its  reflex  life  is  completely  subordinated  to  the  activities  of 
the  association  centers  situated  in  the  more  recently  formed 
cerebral  hemispheres. 


I  • 


Fig.  289.— 
Diagrammatic 
Re  presextatiox 

OF  THE     NeRVOCS 

System    of    the 

CR-A-YFISH. 

A,  Supraeso- 
phageal  gang- 
Uon; B,  commis- 
sure; C,  subeso- 
phageal  ganglion ; 
Z),  first  abdom- 
inal ganglion; 
O,  optic  nerve ; 
72,  middle  nerve; 
P,  antennary 
nerve;  S,  stoma- 
togastric  ner\'e. 


The  Joining  of  the  Reflex  Circuits. — The  struc- 
ture of  the  most  elementary  reflex  arc  has  been  fully 
considered  in  one  of  the  preceding  paragraphs.  It  con- 
sists of  a  receptor,  an  afferent  path,  a  center,  an 
efferent  path  and  an  effector.  Moreover,  it  is  to  be 
noted  that,  in  the  lowest  forms,  these  reflex  circuits 
are  few  in  number  and  retain  a  marked  independency 
of  one  another.  In  the  higher  animals,  on  the  other 
hand,  they  increase  greatly  in  number  and  become 
closely  linked  by  intermediary  neurons  which  thus  es- 
tablish a  close  functional  relationship  between  them. 
The  simple  reflex  arc  (Fig.  290)  may  be  compounded 
first  of  all  into  a  reflex  chain  consisting  of  several  arcs 
{B).  The  impulse  producing  the  primarj^  reflex  response  is  thus  en- 
abled to  spread  and  to  incite  other  responses  until  the  so-called  chain 
reflex  is  obtained.  Another  way  in  which  these  reflex  arcs  may  be 
arranged  is  illustrated  by  Fig.  290,  C.     Here  two  effectors  are  connected 


THE    FUNCTIONAL    UNIT    OF    THE    NERVOUS    SYSTEM 


581 


with  a  single  receptor,  the  efferent  paths  originating  from  a  common 
center.  These  effectors  may  or  may  not  act  in  unison;  i.e.  they  may 
be  alhed  or  antagonistic  in  their  function.  If  the  former  case,  the  re- 
action simply  becomes  more  diversified  and  complex,  but  continues  to 
present  a  perfectly  co-ordinated  character.  An  antagonistic  behavior 
on  their  part,  however,  must  lead  to  a  disconcerted  reaction  which, 
in  most  cases,  can  only  be  prevented  by  inhibiting  the  action  of  one  of 
the  effectors.  Conversely,  two  receptors  may  be  associated  with  only 
one  effector  (D).  If  stimulated  simultaneously,  the  impulses  arising 
in  these  receptors,  will  have  a  tendency  to  interfere  with  one  another 
until  the  more  effective  of  the  two  finally  succeeds  in  gaining  the  com- 
mon path  to  the  effector.     It  may  also  happen  that  these  impulses,  if 


C 


c 


1  I 


£       E 


E 


E 


E 
1? 


V^  m  w 


B 


R    t 


c 


D 


K 


1 


E 


Fig.  290. — Dl\gram    Illustrating    the    Joining    of    Reflex  Circuits. 
/?,  Receptor;  C,  center;  E,  effector. 

simultaneously  elicited,  reinforce  one  another  so  that  the  response 
becomes  much  greater  than  it  would  have  been  if  only  one  of  them  had 
been  received.  Reflex  arcs  may  also  be  combined  into  the  form 
represented  by  Fig.  290,  E.  We  observe  here  that  the  successive 
circuits  are  brought  into  close  relation  with  one  another  by  connecting 
paths,  so  that  the  stimulus  applied  to  one  of  them  may  skip  either  to  the 
same  or  to  neighboring  effectors,  or  both.  In  this  way,  much  more 
complicated  reflexes  may  be  elicited  which,  although  for  the  most  part 
allied,  may  at  times  assume  an  antagonistic  character. 

It  will  be  pointed  out  in  a  subsequent  paragraph  that  the  spinal 
cord,  in  combination  with  the  spinal  nerves  and  those  apportioned  to 
the  sympathetic  system,  is  especially  well  adapted  for  reflex  action. 
In  fact,  as  the  cord  really  consists  of  a  large  number  of  reflex  centers 


582  SIGNIFICANCE    OF   THE    NERVOUS   SYSTEM 

and  their  connecting  paths,  it  is  commonly  regarded  as  one  of  the 
chief  reahns  of  reflex  action.  This  statement,  however,  is  not  meant 
to  convey  the  idea  that  the  cerebrmn  and  other  complexes  of  the 
nervous  system  are  composed  exclusively  of  reaction  circuits,  and  are 
devoid  of  reflex  circuits.  Such  an  assumption  could  easily  be  proved 
to  be  incorrect,  because  many  of  the  most  common  reflexes  invade  the 
cerebrmn  and  neighboring  parts.  For  example,  if  the  intensity  of  the 
Ught  is  increased,  the  pupil  is  constricted,  or  if  the  cornea  is  touched, 
the  eyelids  are  closed.  Similarly,  we  react  to  sound  impressions  quite 
frequently  by  movements  of  the  head,  and  to  visual  impressions  by  a 
hyperproduction  of  saliva  and  gastric  juice.  In  all  these  instances,  as 
well  as  in  many  others  that  might  still  be  mentioned,  at  least  a  section 
of  the  reflex  circuit  is  situated  in  the  realm  of  the  cerebrum  and  parts 
immediately  adjoining.  Nevertheless,  these  actions  are  thoroughly 
reflex  in  their  nature.  As  additional  proof  it  might  be  mentioned 
that  a  group  of  reflexes,  known  as  the  association  reflexes,  actually 
necessitate  the  formation  of  distinct  sensory  concepts,  otherwise 
the  motor  response  invariably  fails  to  develop.  This  is  true,  for 
example,  of  the  act  of  yawning  elicited  by  observing  somebody  else 
yawning,  and  of  the  flow  of  saliva  and  gastric  juice  following  the  sight 
of  attractive  food.  In  all  these  cases,  volition  does  not  play  a  part  and 
hence,  it  must  be  concluded  that  reflex  circuits  may  be  found  in  all 
parts  of  the  nervous  system  and  even  in  the  domain  of  the  cerebrum, 
where  they  are  brought  into  relation  with  the  processes  of  conscious- 
ness. It  is  to  be  noted,  however,  that  the  impulses  conveyed  by  them 
do  not  lose  their  reflex  character  unless  dominated  finally  by  voHtion. 
Whenever  this  change  takes  place,  the  reflex  becomes  an  associated 
act  or  a  voHtional  reaction. 

The  conditions  found  in  the  lower  forms  are  most  closely  simulated 
in  the  sympathetic  system,  because  this  system  consists  of  a  series  of 
gangUa  which  are  connected  with  one  another  by  closely  interwoven 
nerve  fibers.  While  these  gangUa  are  generally  situated  in  the  im- 
mediate vicinity  of  the  structures  innervated  by  them,  they  may  also 
be  placed  directly  within  their  substance.  If  we  direct  our  attention 
for  a  moment  to  the  stomach  and  intestine,  we  find  that  these  organs 
may  be  made  to  contract  and  to  secrete  even  outside  the  body,  pro- 
vided that  they  are  kept  under  proper  conditions  of  moisture  and 
temperature.  They  are  thus  proved  to  possess  a  remarkable  independ- 
ency of  function  which  is  made  possible  by  the  fact  that  they  are 
amply  equipped  with  reflex  circuits  which  in  all  probabiHty  are  con- 
tained in  the  plexuses  of  ;Meissner  and  Auerbach.  But  even  if  these 
organs  are  left  in  situ,  it  is  not  difiicult  to  divide  the  bridges  connecting 
them  with  the  cerebrospinal  system.  In  this  way,  voHtion  may  be 
absolutely  excluded  from  them  as  well  as  from  all  other  sympathetic 
organs.  Since  their  functions  are  not  seriously  disturbed  thereby,  it 
must  be  concluded  that  they  are  typically  reflex  in  their  nature. 

Very  similar  conditions  are  met  with  in  the  spinal  cord,  the  reflex 


REFLEX    ACTION  583 

nature  of  which  may  be  more  clearly  portrayed  by  severing  the  con- 
nections between  it  and  the  brain.  This  end  may  be  attained 
by  a  section  made  either  above  or  below  the  medulla  oblongata.  It 
will  be  show^n  later  on  that  an  anhnal  of  this  kind  retains  all  those 
functions  which  are  ordinarily  accomplished  with  the  aid  of  the  cord. 
These  responses,  however,  need  not  remain  confined  to  a  particular 
segment  of  this  structure,  but  may  also  involve  higher  or  lower  spinal 
centers  without  losing  their  reflex  character.  The  reactions  of  a 
"spinal  cord  animal"  must  necessarily  be  non-volitional. 

When  referring  to  reflex  circuits  and  actions  we  are  accustomed 
to  associate  them  immediately  with  the  spinal  cord.  The  preceding 
discussion,  however,  must  have  made  it  clear  that  they  are  not  ex- 
clusively confined  to  this  structure,  but  may  involve  almost  any  part 
of  the  nervous  system.  It  seems  that  the  spinal  cord  is  referred  to 
most  frequ(mtly  in  this  connection,  because  it  is  a  relatively  simple 
matter  to  isolate  it  and  to  stimulate  its  nerves.  Moreover,  the  spinal 
reflexes  are  perfectly  conscript  actions  and  pursue  easily  recognizable 
paths. 


CHAPTER  XL VIII 
REFLEX  ACTION^ 


The  Different  Types  of  Effectors  and  Receptors. — If  we  adhere  to 
the  general  definition  that  a  reflex  is  a  non-volitional  motor  response 
to  a  sensory  impulse,  the  very  diverse  and  complex  character  of  these 
reactions  must  immediately  become  evident.  On  the  efferent  side, 
of  course,  conditions  are  relatively  simple,  because  the  effectors  consist 
of  only  two  structural  units,  namely,  the  muscle  cell  and  the  gland 

1  The  term  sympathy  or  consensus  was  applied  by  the  ancients  to  almost  all 
phenomena  of  life.  In  1649,  however,  Descartes  separated  from  these  general 
reactions  all  those  which  did  not  produce  an  impression  in  consciousness  and  were 
not  subjected  to  the  will.  He  applied  to  this  class  of  reactions  the  term  reflex, 
because  in  analogy  to  the  reflection  of  light,  the  sensory  impression  seemed  to  be 
returned  in  the  form  of  a  motor  effect.  Subsequent  to  this  time,  Willis  (1664), 
Astrue  (1743),  and  Unzer  (1771)  have  described  various  reflexes  such  as  the  acts  of 
coughing,  sneezing,  the  closure  of  the  eyelids,  the  ejaculation  of  the  semen,  and 
others.  Their  idea,  however,  seemed  to  be  that  these  reactions  can  be  brought 
about  with  the  help  of  the  nerve  trunks  and  do  not  require  a  center.  AMij^tt 
(1751)  then  proved  that  this  conception  is  incorrect,  because  in  the  frog  the 
destruction  of  the  spinal  cord  immediately  destroys  the  reflex  actions  ordinarily 
elicited  with  the  help  of  this  part  of  the  nervous  system.  He  also  described  the 
reflex  secretion  of  the  tears  and  of  saliva,  and  recognized  the  fact  that  the  latter 
may  also  be  obtained  by  psychic  stimulation;  in  other  words,  he  recognized  the 
association  reflex.  The  modern  conception  of  reflex  action  is  based  upon  the  work 
of  M.  Hall  (1832-33)  and  Joh.  Mliller  (1833-34). 


584  SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 

cell.  The  formcn-  gives  rise  to  motion  and  the  latter  to  secretion. 
It  must  be  rememljered,  however,  that  the  muscle  cell  presents  itself 
in  three  forms,  giving  rise  respectively  to  the  striated,  non-striated 
and  cardiac  tissue,  and  furthermore,  that  especially  the  second  type 
of  muscle  cell  is  a  constituent  of  a  most  perplexing  array  of  structures. 
Thus,  we  find  it  in  the  iris,  ciliary  body,  stomach,  intestines,  blood- 
vessels, ureter,  bladder,  sexual  organs,  skin,  etc.  In  all  these  cases 
it  responds  to  stimuli  by  contracting,  but  the  effect  produced  thereby 
differs  greatly  in  accordance  with  the  general  arrangement  of  the  tissue 
in  which  it  is  embedded.  Clearly,  the  movement  shown  by  the  iris, 
is  different  in  character  from  that  of  the  contracting  stomach  or  blad- 
der. The  same  is  true  of  the  gland  cell.  While  representing  only 
one  type  of  effector,  this  cell  appears  in  various  forms  as  a  unit  of  the 
multitude  of  the  glandular  structures  present  in  our  body.  Its  stimu- 
lation, therefore,  must  give  rise  to  secretions  of  very  different  appear- 
ance and  composition.  Thus,  while  it  is  customary  to  illustrate  reflex 
action  with  the  help  of  motion,  and  especially  with  that  type  of  it  which 
is  caused  by  striated  muscle,  it  should  not  be  forgotten  that  the  body 
is  also  in  a  position  to  give  a  multitude  of  secretory  responses. 

The  conditions  met  with  on  the  afferent  side  of  the  reflex  circuit, 
betray  a  much  greater  diversity  of  structure  and  function.  The 
layman  commonly  states  that  there  are  five  sense  organs  present  in 
our  body,  namely  the  eyes,  ears,  nose,  tongue  and  skin.  We  shall 
find,  however,  that  these  five  so-called  external  senses  are  augmented 
by  about  twenty  others  which  are  chiefly  concerned  with  the  impres- 
sions brought  to  bear  upon  internal  parts.  It  appears,  therefore,  that 
the  two  effector  units,  the  muscle  and  the  gland  cell,  are  opposed  by 
more  than  twenty  receptors,  every  one  of  which  presents  very  special 
structural  characteristics.  Motion  or  secretion  are  thus  given  in 
answer  to  sensory  impressions  received  from  a  relatively  great  number 
of  diversified  receptors.' 

The  Reflex  Animal. — In  studying  reflex  action,  it  is  customary  to 
make  use  of  a  frog,  the  brain  of  which  has  been  removed  or  destroyed 
by  the  process  of  pithing.  Obviously,  this  procedure  destroys  the 
"psychic"  life  of  this  animal  and  renders  its  actions  absolutely  non- 
volitional.  An  animal  of  this  kind,  therefore,  is  incapable  of  ex- 
periencing pain  or  of  receiving  any  other  sensation  in  consciousness. 
In  the  absence  of  the  cerebrum,  an  afferent  impulse  must  necessarily 
remain  a  simple  reflex  sensation.  The  removal  of  the  cerebral  hemi- 
spheres, therefore,  serves  the  purpose  of  converting  the  frog  into  a 
simple  reflex  animal. 

The  reflexes  commonly  studied  subsequent  to  this  procedure,  are 
those  occurring  in  the  domain  of  the  spinal  cord,  i.e.,  the  so-called 
spinal  reflexes.  The  frog  is  suspended  from  a  hook  passed  through 
its  lower  maxilla.     The  sole  of  the  foot  is  then  stimulated  either  bj'" 

1  A  further  discussion  regarding  the  structure  of  receptors  will  be  found  upon 
page  729. 


REFLEX    ACTION  585 

applyinp;  the  oloctrodcs  lijjjiitly  to  its  surface  or  by  pinching  the  skin 
with  a  pair  of  forceps.  If  more  convenient,  the  foot  may  be  immersed 
in  a  weak  solution  of  acetic  acid.  In  either  case,  the  stimulus  pres- 
ently p;ives  rise  to  a  contraction  of  the  muscles  of  the;  corresponding 
leg;  whicii  results  in  its  withdrawal  from  the  scat  of  the  stimulation. 
If  electrical  stimuli  are  employed,  the  student  should  sharply  dif- 
ferentiate between  the  direct  effect  of  the  current  as  evinced  by  a 
twisting  of  the  toes,  and  the  reflex  effect,  consisting  in  a  more  general 
muscular  action  and  the  actual  withdrawal  of  the  leg.  It  should  also 
be  observed  that  the  stimulus  is  applied  in  this  case  to  the  tactile 
receptors  of  the  skin  and  that  the  response  consists  in  a  seemingly 
purposeful  movement.  This  reaction  is  similar  to  the  one  occurring 
in  us  whenever  our  integument  is  suddenly  stimulated,  say,  in  a  me- 
chanical way.  The  subsequent  contraction  of  the  musculature 
necessary  to  perform  the  protective  movements  corresponding  to 
this  stimulus,  is  non-volitional,  i.e.,  the  response  is  had  without  that 
its  character  can  be  changed  by  the  will.  In  many  cases,  of  course, 
we  obtain  a  perfect  sensory  concept  of  this  act,  but  the  sensorium  is 
activated  in  this  instance  after  the  completion  of  the  primary  act 
and  cannot,  therefore,  influence  the  latter  in  any  way.  Biit  if  this 
cutaneous  stimulus  is  first  received  in  consciousness  and  is  there 
subjected  to  volition,  the  resulting  response  ceases  to  be  a  reflex  and 
becomes  a  complex  reaction. 

Reflex  Time.  Reflex  Fatigue.  —  The  time  elapsing  between 
the  moment  of  the  application  of  the  stimulus  and  the  beginning  of  the 
response,  is  known  as  the  reflex  time.  As  is  easily  observed  in  the  re- 
flex frog,  this  factor  varies  with  the  strength  of  the  stimulus  and 
the  irritability  of  the  nervous  system.  It  has  been  stated  above  that 
a  series  of  slight  stimuli  are  more  effective  than  one  strong  one,  and 
that  the  best  results  are  obtained  if  the  receptor  itself  is  stimulated 
and  not  the  afferent  path  leading  from  it.  Thus,  if  a  tetanic  current 
of  very  moderate  strength  is  applied  to  the  sole  of  the  foot  of  the  reflex 
frog,  a  perfectly  definite  muscular  response  is  evoked,  consisting  in  a 
seemingly  purposive  removal  of  the  foot  from  the  seat  of  stimulation. 
There  is,  of  course,  no  intent  present,  because  this  result  is  wholly 
dependent  upon  the  general  structural  arrangement  of  the  leg.  If 
the  intensity  of  the  stimulus  is  now  increased,  the  response  follows  with 
the  same  mechanical  precision,  but  at  a  somewhat  earlier  moment. 
In  other  words,  the  reflex  time  is  inversely  proportional  to  the  strength 
of  the  stimulus.  It  is  also  possible  to  vary  the  reflex  time  by  altering 
the  receptive  power  or  irritability  of  the  nervous  system.  Depressive 
agents,  such  as  the  narcotics,  lengthen  it,  while  stimulants,  such  as 
strychnin,  oxygen,  warmth,  etc.,  shorten  it. 

We  are  thus  justified  in  applying  to  reflex  action  such  characteriza- 
tions as  ''subminimal  reflex  stimulus,"  meaning  thereby  the  stimulus 
wliich  just  fails  to  elicit  a  reflex  response,  or  "reflex  threshold,"  indi- 
cating thereby  the  stimulus   wliich  is  just   becoming  effective.     It 


586  SIGNIFICANCE    OF   THE    NERVOUS    SYSTEM 

is  also  evident  that  the  repeated  elicitation  of  a  certain  reflex  is  very- 
prone  to  lengthen  the  reflex  time  and  to  lessen  its  conspicuousness, 
because  the  structures  participating  in  this  reaction  become  fatigued. 
We  are  thus  forced  to  recognize  the  condition  of  "reflex  fatigue,"  and 
to  admit  that  reflexes  also  possess  a  definite  "refractory  period." 
This  imphes  that  they  cannot  be  elicited  at  shorter  intervals  than  are 
rcjquired  for  the  anabolic  changes  in  the  different  elements  of  the  reflex 
circuit. 

*  In  all  these  cases,  the  cell-body,  rather  than  the  conducting  paths, 
seems  to  be  the  deciding  factor.  It  is  to  be  noted,  however,  that  the 
reflex  time  includes  several  elements,  namely,  the  time  of  conduction 
of  the  impulse  through  the  afferent  and  efferent  paths,  its  passage 
through  the  center  and  lastly,  the  latent  period  of  the  motor  organ. 
Helmholtz^  has  shown  that  the  transfer  of  the  impulses  through  the 
gray  matter  of  the  spinal  cord  consumes  twelve  times  as  long  a  time 
as  their  passage  through  the  peripheral  conducting  channels.  The 
total  reflex  time  may  thus  be  regarded  as  being  composed  of  the 
"rough"  and  "reduced"  reflex  phases.  The  former  includes  the 
time  elapsing  between  the  moment  of  stimulation  of  the  receptor 
and  the  onset  of  the  response,  and  the  latter,  the  time  consumed 
by  the  processes  occurring  in  the  center,  i.e.,  the  total  time  less  the 
time  of  conduction  over  the  afferent  and  efferent  paths  and  the  length 
of  the  latent  period  of  the  motor  organ.  Exner,^  for  example,  states 
that  the  closure  of  the  eyelids  upon  stimulation  of  the  cornea  (corneal 
reflex)  occupies  0.0578-0.0662  second.  As  the  conduction  requires 
in  this. case,  0.0107  second,  the  central  transfer  must  consume  0.0471- 
0.0555  second.  Listing  and  Vintschgau^  estimate  the  time  of  the 
reaction  of  the  iris  to  varying  intensities  of  light  (light  reflex)  at  0.3-0.4 
second.  The  reactions  accomplished  with  the  aid  of  smooth  muscle, 
are  much  slower,  a  fact  which  is  in  keeping  with  the  lesser  irritability  of 
this  tissue  as  well  as  of  the  nervous  elements  innervating  it.  This 
is  especially  true  of  the  sympathetic  system. 

Spreading  or  Crossing  of  Reflexes. — If  the  stimulus  applied  to  the 
foot  of  a  reflex  frog,  is  of  slight  intensity,  the  leg  is  withdrawn  in  a 
gradual  and  easy  manner,  while  if  the  stimulus  is  severe,  the  leg  is 
jerked  up,  and  besides,  the  muscular  contractions  do  not  remain 
confined  to  this  Hmb,  but  spread  to  the  muscles  on  the  opposite  side 
and  possibly  also  to  those  of  the  trunk  and  forelegs.  This  result  indi- 
cates that  the  primary  afferent  impulse  has  been  transferred  to  other 
reflex  circuits,  or  better,  that  the  primary  reflex  has  led  to  an  activa- 
tion of  those  reflex  circuits  which  are  in  functional  relation  with  the  one 
involved  first.  In  order  to  allow  this  spreading  to  take  place,  certain 
intermediary  neurons  must  be  present,  the  purpose  of  which  is  to 

'  Prot.  der  Akad.  d.  Wissensch.,  Berlin,  1845;  also  Fano,  Arch.  ital.  de  biol., 
xx.xix,  1903,  85. 

2  Pfliiger's  Archiv,  viii,  1874,  526. 
'  Ibid.,  xxvi,  1881,  324. 


REFLEX    ACTION 


587 


conduct  the  iinpulsos  up  or  down  in  the  spinal  cord.  This  arrange- 
ment is  clearly  indicated  in  Figs.  291,  292 
and  293.  Tlie  first  two  illustrate  the  conduc- 
tion paths  required  for  a  simple  reflex  in  which 
a  single  ])ost('rior  extremity  is  involved.     In 


Fig.  291,  Fig.  292, 

Fig.  291. — Schema  to  Illustrate  Slmple  Reflex  Conduction  in  the  Spinal  Cord. 
A,  The  sensory  impulse  is  immediately  transferred  to  the  motor  path  E. 
Fio.  292. — Schema  to  Show  Simple  Reflex  Conduction  in  the  Spinal  Cord. 
A,  The  sensory  impulse  is  transferred  in  the  anterior  horn  to  the  motor  neuron  E. 


this  case,  the  impulse  arriving  by  way  of  the 
mediately  transferred  to  the  motor  neuron  in 
the  anterior  horn  of  the  gray  matter,  and 
from  here  to  the  corresponding  effector. 
Figure  293  shows  how  intermediary  neurons 
enable  the  impulse  to  attain  higher  or  lower 
levels  of  the  spinal  cord,  where  connections 
are  formed  with  the  motor  cells  and  effectors 
situated  at  a  more  remote  distance  from  the 
primary  circuit.  The  spreading  of  a  reflex  to 
adjoining  arcs  may  be  demonstrated  in  various 
ways.  If  the  leg  of  a  frog  "to  which  a  stimulus 
has  been  apphed,  is  firmly  held  in  place  so 
that  the  motor  effects  cannot  fully  develop 
on  this  side,  the  primary  action  eventually 
spreads  to  the  muscles  of  the  opposite  limb  as 
well  as  those  of  the  trunk  and  forelimbs.  It 
is  also  possible  to  ehcit  this  phenomenon  by 
stimulating  the  central  end  of  the  divided 
sciatic  nerve  of  one  side.  As  this  section  ren- 
ders the  muscles  of  the  same  side  functionally 
useless,  the  afferent  impulses  generated  at  the 
seat  of  the  stimulation,  find  their  way  into 
the  motor  paths  of  the  opposite  leg  as  well 
as  into  those  of  the  trunk  and  forelimbs. 

In  general,  it  may  be  said  that  reflexes  may 


sensory  neuron,  is  im- 


FiG.  293. — Schema  to 
Illustrate  Reflex 
Spreading  in  the  Spinal 
Cord. 

A,  The  sensory  impulse 
is  transferred  to  an  inter- 
mediary neuron  j  which 
conveys  it  to  higher  and 
lower  motor  paths  E. 


be  made  to  spread  (a) 


588  SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 

by  increasing  the  intensity  of  the  stimulus,  and  (b)  by  heightening  the 
irritabiUty  of  the  nervous  structures.  The  latter  effect  may  bo  evoked 
by  any  agent  possessing  a  stimulating  action  upon  the  nervous  system, 
such  as  a  weak  solution  of  the  sulphate  of  strychnin.  If  this  drug  is 
injected  under  the  skin  covering  the  dorsal  aspect  of  the  frog,  its  grad- 
ual absorption  finally  leads  to  an  increased  susceptibility  to  stimuli 
wliich  is  clearly  betrayed  by  the  extensive  and  intense  muscular  spasms 
resulting  in  consequence  of  even  the  slightest  possible  tactile  or  elec- 
trical stimulus.  The  mere  touch  of  the  plate  upon  wliich  the  strych- 
ninized  frog  has  been  placed  or  a  current  of  air  blown  across  the  surface 
of  its  body,  now  suffices  to  throw  every  muscle  into  a  state  of  prolonged 
contraction.  The  explanation  usually  given  for  this  effect  is  that  the 
strychnin  lessens  the  resistance  to  conduction.  It  is  said  to  accomplish 
this  end  by  increasing  the  continuity  in  the  synapses,  i.e.,  it  is  sup- 
posed to  bring  the  axon  and  dendritic  terminals  into  closer  relationship 
so  that  the  impulses  are  enabled  to  spread  more  readily  from  neuron  to 
neuron. 

Inhibition  of  Reflexes. — This  phenomenon  consists  in  a  lessening 
and  final  abolition  of  the  motor  response  following  the  apphcation 
of  a  stimulus.  It  is  commonly  believed  that  this  depression  is  brought 
about  by  a  blocking  of  the  reflexes  in  their  respective  centers.  The 
impulses  which  accomplish  this  end  are  derived  from  different  sources, 
namely,  (a)  from  the  faculty  of  volition  in  the  cerebral  hemispheres, 
(6)  from  higher  reflex  centers  situated  in  the  midbrain  and  hindbrain, 
(c)  from  peripheral  nerves,  and  (d)  from  a  lessening  of  the  irritability 
of  the  nervous  system  as  a  whole. 

Cerebral  Inhibition. — It  is  a  matter  of  common  experience  that  reflexes  may  be 
suppressed  by  volitional  efforts.  While,  under  ordinary  conditions,  a  touch  upon 
the  cornea  gives  rise  to  a  quick  closure  of  the  eyelids,  special  efforts  may  be  made 
to  overcome  this  stimulus.  In  a  similar  manner,  we  may  counteract  the  stimulus 
which  ordinarily  gives  rise  to  the  act  of  coughing  or  sneezing.  It  seems,  however, 
that  this  cerebral  inhibition  necessitates  two  conditions,  namelj%  that  the  excita- 
tion be  of  moderate  intensity,  and  that  the  reflex  which  we  endeavor  to  suppress, 
be  in  functional  relation  with  volition.  It  must  be  evident  that  a  strong  excitation 
must  eventually  overcome  even  very  powerful  counter  efforts  and  furthermore,  as 
a  large  number  of  our  reactions  are  not  under  the  guidance  of  the  will  at  anj^  time, 
it  must  be  clear  that  volitional  efforts  cannot  be  brought  to  bear  upon  them. 
This  exception  applies  especially  to  the  motor  end-organs  consisting  of  smooth 
muscle  tissue  and  situated  in  the  domain  of  the  sympathetic  system.  Thus,  we 
are  quite  unable  to  inhibit  vasomotor  and  pilomotor  reactions  or  to  vary  the  size 
of  our  pupils  in  antagonism  to  the  stimulations  received  from  the  retinae.  This 
exception  is  also  apparent  in  the  case  of  several  striated  muscles,  because  we  are 
unable  to  influence  the  cremasteric  reflex  and  to  counteract  the  contraction  of  the 
muse,  bulbocavernosus. 

The  inhibitory  power  of  the  cerebral  cortex  upon  reflex  action  is  well  illustrated 
by  the  changes  in  the  "croaking  reflex"  of  the  frog  occurring  in  consequence  of  the 
removal  of  the  hemispheres.  Under  normal  conditions,  this  act  necessitates  a 
certain  psychic  activity.  "•     It  is  dependent  upon  certain  elementary  associations 

1  Goltz,  Beitrag  zur  Lehre  von  den  Funktionen  der  Nervenzentren  des  Frosches, 
Berlin,  1863. 


REFLEX    ACTION  589 

and  is  executed  volitiomilly.  The  removal  of  the  cerebrum  converts  this  previously 
complex  reaction  into  a  pure  reflex,  as  may  be  gathered  from  the  fact  that  the 
decerel)rated  frog  produces  this  sound  at  any  time  in  consequence  of  such  cuta- 
neous stinudations  as  the  stroking  of  the  skin  of  the  dorsum  or  the  application  of  a 
gentle  pressure  to  the  sitles  of  the  alxlomen.  Mcjreover,  this  reflex  may  be  repeated 
almost  any  number  of  times  until  reflex-fatigue  causes  it  to  cease.  Another  ex- 
periment illustrating  cerei)ral  inhibition  of  reflexes,  is  the  following:  When  the 
female  frog  de]iosits  its  eggs,  the  male  endeavors  as  a  rule  to  aid  its  mate  by 
firndy  clasping  her  abdomen  with  his  fore  limbs.  This  reaction  on  the  part  of  the 
male  may  be  converted  into  a  reflex  l)y  removing  the  cerebrum,  as  is  evinced  by  the 
fact  that  the  decerebrated  male  may  lie  made  to  clasp  objects  of  any  kind  by  sim- 
ply bringing  them  in  contact  witli  the  ventral  aspect  of  his  thorax.  In  fact,  it  is 
possil>le  to  produce  this  reflex  even  in  the  ab.sencc  of  all  parts  excepting  the  thorax 
and  the  two  forelimbs.  In  the  higher  animals,  the  removal  of  the  cerebrum 
distinctly  shortens  the  time  of  the  spinal  reflexes  and  leads  to  the  appearance  of 
certain  reflexes  which  imder  normal  conditions  are  scarcely  perceptible.  Such 
acts  as  licking,  scratching,  growling,  etc.,  then  assume  a  clear  reflex  character, 
because  the  influence  of  volition  has  been  permanently  removed  from  them. 

Inhibition  by  the  Midbrain. — It  has  been  assumed  that  reflex  action  is  regulated 
by  a  higher  center  which,  in  accordance  with  Setschenow,i  is  located  in  the  mid- 
brain, i.e.,  in  the  optic  lobes  of  such  animals  as  the  amphibia  and  reptilia.  This 
conclusion  is  based  upon  the  observation  that  the  removal  of  this  part  of  the 
nervous  system  shortens  the  time  of  the  spinal  reflexes  and  renders  them  more 
vivid.  The  opposite  effect  may  be  produced  by  stimulating  these  bodies  while 
eliciting  any  one  of  the  spinal  reflexes.  The  evidence,  however,  seems  to  be  against 
the  existence  of  specific  inhibitory  centers  for  reflex  action.  Instead,  it  is  generally 
assumed  that  the  optic  lobes  (corpora  quadrigemina)  and  other  bodies,  are 
enabled  to  unfold  this  faculty  in  consequence  of  their  connection  with  the  chief 
conducting  channels  passing  to  and  from  the  cerebral  hemispheres.  In  the  lower 
vertebrates,  they  are  of  even  greater  importance,  because  they  give  origin  to  the 
optic  nerves.  It  is  only  natural  to  suppose  that  the  sensory  impressions  derived 
from  this  source  must  tend  to  hinder  simple  reflex  action  even  in  the  absence  of 
special  inhibitory  centers.  It  seems,  therefore,  that  this  form  of  inhibition  may  be 
most  easih'  explained  upon  the  basis  of  a  central  interference  of  different  afferent 
impulses  with  one  another. 

Inhibition  by  Other  Afferent  Impulses. — It  is  a  well  recognized  fact  that  reflexes 
may  be  inhibited  by  simultaneous  afferent  impulses.  The  act  of  sneezing  may  be 
suppressed  by  exerting  a  gentle  pressure  upon  the  upper  lip  or  by  rubbing  the  nose. 
Quite  similarly,  a  mechanical  stimulus  to  the  skin  may  be  rendered  abortive  by  a 
second  stimulus  applied  elsewhere  to  the  integument.  Thus,  it  may  easily  be 
shown  that  the  reflex  caused  by  stimulating  the  sole  of  the  frog's  foot,  may  be  com- 
pletely inhibited  by  the  simultaneous  excitation  of  the  central  end  of  the  opposite 
sciatic  nerve.  In  the  absence  of  distinct  inhibitory  reflex  centers  and  ner\^es,  these 
results  can  onh^  be  explained  upon  the  basis  of  an  interference  of  impidses,  result- 
ing, as  has  been  more  fully  discussed  above,  in  the  ganglion  cells  of  the  reflex  cir- 
cuit involved  in  this  particular  act.  In  consequence  of  the  refraction  of  the  cell, 
one  of  these  impulses  is  rendered  ineffective. 

Strong  and  continued  stimulation  of  sensory  nerves  eventually  leads  to  a 
depression  and  complete  abolition  of  almost  all  reflexes.  This  condition  is  known 
as  "shock,"  and  if  the  immediate  cause  of  this  depression  is  located  in  the  realm 
of  the  spinal  cord,  as  spinal  shock. 

Shock.^ — A  person  in  shock  is  usually  found  in  a  state  of  complete  muscular 

^Physiol.  Studien  liber  die  Hemmungsmechanismen,  etc.,  Berlin,  1863.  Meltzer, 
The  role  of  inhibition  in  normal  and  pathological  phenomena  of  life,  Med.  Record, 
1902. 

-  Short,  Lancet,  1914,  and  Wiggers,  Am.  Jour.  Med.  Sciences,  clii,  1917,  666. 


590  SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 

relaxation  and  if  movements  are  made,  they  are  feeble  and  irregular.  The 
face  is  pale  and  drawn,  the  pupils  dilated,  sweating  is  often  profuse,  the  reflexes  are 
slight,  consciousness  is  usually  present  but  there  is  a  diminished  sensibility  and 
mental  activity.  The  respirations  are  feeble,  irregular  and  sighing.  The  pulse  is 
small,  frequent  and  dicrotic,  owing  to  the  low  blood  pressure.  The  skin  is  cold  and 
the  temperature  subnormal.  The  theories  which  have  been  brought  forth  in  ex- 
planation of  this  phenomenon,  may  be  grouped  as  follows: 

(a)  Exhaustion  of  the  vasomotor  mechanism  by  a  depression  of  the  activities 
of  the  center.  This  theory  is  not  satisfactory  because  while  shock  commonly  in- 
duces a  fall  in  blood  pres.sure,  the  vasomotor  center  is  not  exhausted  and  the  blood- 
vessels may  be  constricted;  moreover,  the  heart  is  not  seriously  affected,  although 
its  output  is  small. 

(b)  Acapnia,  or  deficiency  in  CO2,  removes  a  most  important  stimulus  from 
different  nerve  centers.  The  breathing  becomes  .shallow  and  occasional,  the  blood- 
pressure  falls  and  the  heart  beats  more  quickly.  The  objections  to  this  theory  are 
many,  chief  among  which  is  that  shock  should  then  be  prevented  by  artificially 
supplying  CO-,  which  is  not  the  case. 

(c)  Oligemia,  or  too  little  blood,  acts  by  reducing  the  blood  pressure,  but  allows 
the  cardiac  and  vasomotor  centers  to  continue  their  activities.  Gravity  shock  may 
be  classified  under  this  heading,  because  it  is  caused  by  a  stagnation  of  blood  in  the 
splanchnic  blood-vessels  and  consequent  inadequate  filling  of  the  heart.  Thus, 
when  a  rabbit  with  a  large  pendulous  abdomen  is  held  vertically  with  the  head  up 
for  any  length  of  time,  it  frequently  passes  into  the  condition  of  shock  and  may  die 
within  20  to  30  minutes. 

{d)  Exhaustion  of  adrenin,  brought  about  by  an  initial  outpouring  of  excessive 
amounts  of  adrenin  in  consequence  of  sensory  stimulation.  This  finally  leads 
to  its  exhaustion. 

(e)  Inhibition  of  the  activity  of  the  nuclei  of  the  spinal  cord  and  midbrain.^ 
^Yhen  such  an  inhibition  takes  place,  the  function  of  the  cord  is  greatly  diminished. 
Consequently,  its  constituent  nuclei  cease  sending  out  those  impulses  which  main- 
tain the  tonus  of  the  muscles.  The  blood  pressure  falls.  Even  the  respiratory 
center  shares  in  the  paralysis.  Eventually  a  venous  engorgement  is  obtained 
which  makes  a  proper  filling  of  the  heart  and  arterial  channels  impossible.  Spinal 
shock,  however,  possesses  a  rather  local  character,  because  it  affects  only  those 
parts  of  the  body  which  lie  below  the  seat  of  the  spinal  lesion.  Under  this  heading 
may  be  classified  the  so-called  nervous  shock  or  shell  shock,  as  well  as  the  shock 
accompanj-ing  overdoses  of  anesthetics.  In  the  latter  case,  however,  the  reflexes 
reappear  after  the  discontinuance  of  the  narcosis,  while  in  surgical  shock  they  do 
not. 

Inhibition  in  Consequence  of  the  Lessening  of  the  Irritability  of  the  Nervous 
System.^This  condition  results  during  sleep  and  narcosis.  The  reflexes  which  are 
abolished  first,  are  the  abdominal,  cremasteric  and  patellar,  while  those  from  the 
sole  of  the  foot  and  from  the  nasal  mucosa  are  more  resistant.  The  reflexes  which 
disappear  last  are  the  corneal  and  retinal.  For  this  reason,  sleep  and  narcosis 
may  be  employed  as  a  means  to  determine  whether  or  no  an  action  is  a  true  reflex, 
because  if  it  persists  during  these  states  of  cerebral  depression,  it  must  be  non- 
volitional.  In  infants  and  children  this  weakening  of  the  reflexes  is  less  e\-ident 
than  in  adults.  It  need  scarcely  be  mentioned  that  the  intensity  of  the  reflexes 
may  be  made  to  serve  as  an  index  of  the  depth  of  the  narcosis.  The  reactions 
usually  employed  for  this  purpose  are  the  corneal  and  pupillar  (light)  reflexes,  the 
danger  line  being  reached  when  a  mechanical  impact  upon  the  cornea  very  nearly 
fails  to  elicit  a  contraction  of  the  muse,  orbicularis  palpebrarum  and  when  imme- 
diately thereafter  the  pupils  become  con.stricted.  A  weakening  and  final  inhibition 
of  the  reflexes  also  results  in  coma  and  depressions  of  the  ner^-ous  sj'stem  resulting 

iPike,  .\m.  Jour,  of  Physiol.,  xxx,  1912,  4.36,  and  Porter  and  Miihlberg,  ibid., 
iv,  1900,  334. 


REFLEX    ACTION  591 

from  cerebral  concussion  and  the  al)S()rpti()n  of  toxic  asents.  such  as  incrotoxin, 
morphin,  (luinin,  potassium  l)romi(l,  and  others. 

Acceleration  and  Conditioning  of  Reflexes. — Certain  conditions 
may  arise  at  times  which  will  tend  to  augment  reflex  action  in  such 
a  degree  that  it  becomes  difficult  to  differentiate  these  responses  from 
those  previously  described  under  the  heading  of  spreading  of  impulses. 
The  causes  to  which  this  accc^leration  ma}^  be  assigned  an;  twofold. 
Thus,  it  may  be  caused  either  by  an  increase  in  the  strength  of  the 
stimulus  or  by  a  heightened  irritability  of  the  nervous  tissue.  If  an 
irritant  is  applied  to  the  nasal  mucosa  of  a  strength  just  sufficient  to 
incite  merely  a  slight  tendency  to  sneeze,  this  primary  stimulus  may  be 
reinforced  by  the  act  of  sniffing.  Clearly,  as  this  augmentation  is  de- 
pendent upon  volition,  it  must  be  attained  with  the  help  of  the  cere- 
brum. We  are  also  in  a  position  to  strengthen  those  reflexes  which 
ordinarily  result  in  consequence  of  cutaneous  impressions,  either  by 
the  apphcation  of  cold  water  or  by  stimuli  involving  the  optic  or 
auditory  mechanism.  In  a  similar  manner,  the  corneal  reflex  may  be 
accelerated  by  gently  blowing  a  current  of  air  across  the  surface  of  the 
conjunctiva.  On  the  whole,  however,  it  must  be  conceded  that  reflex 
acceleration  cannot  be  effected  so  easily  as  reflex  inhibition. 

By  far  the  largest  number  of  reflexes  are  not  conditioned.  A 
particular  kind  of  stimulus  gives  rise  to  a  particular  reaction  with 
almost  mechanical  exactitude.  This  is  true  of  coughing,  sneezing, 
yawning  and  other  acts  with  which  we  are  familiar.  It  is  possible, 
however,  to  subject  these  reflexes  to  other  influences  so  that  they 
assume  an  elaborated  or  conditional  character.^  Thus,  we  are  able  to 
incite  a  flow  of  saliva  quite  readily  by  the  introduction  of  a  drop  of 
dilute  acetic  acid  into  the  mouth  of  the  subject.  If  this  stimulation 
is  repeated  a  number  of  times  at  intervals  and  if  this  stimulation  is 
accompanied  by  a  visual  impression,  such  as  may  be  effected  by  a 
receptacle  filled  with  colored  water,  the  primary  stimulus  may  be 
dispensed  with  in  time,  because  the  retinal  stimulus  alone  will  then 
suffice  to  produce  the  aforesaid  result.  While  many  of  our  reflexes 
may  be  conditioned  in  one  way  or  another,  it  is  true  that  this  cannot 
be  done  without  the  help  of  perception.  In  other  words,  the  condi- 
tioned reflexes  require  training  or  education.  This  conversion  of  a 
simple  reflex  into  an  association  reflex,  however,  does  not  necessitate 
the  participation  of  voHtion;  in  fact,  it  precludes  this  modification 
for  the  reason  that  the  reflex  would  then  lose  its  primitive  character 
and  become  a  reaction. 

Classification  of  Reflexes. — In  accordance  with  their  qualitative 
peculiarities,  reflexes  are  divided  into: 

(a)  Simple  reflexes,  in  which  a  single  muscle  or  glandular  unit  is  involved.  As 
an  example  of  this  kind  of  response  might  be  mentioned  the  corneal  reflex.  The 
afferent  arc  is  formed  by  the  ner\-i  ciliares  trigemini  and  the  efferent  arc  by  the 

1  Pawlow,  Livre  jubil.  du  Prof.  C.  L.  Richet,  1912. 


592  SIGNIFICANCE    OF    THE    NERVOUS    SYSTEM 

orbicular  branches  of  the  facial  nerve.  The  effector  is  the  muse,  orbicularis 
palpebrarum. 

(6)  Complex  reflexes,  in  which  several  muscles  or  secretory  units  are  affected,  but 
the  response  remains  perfectly  co-ordinated,  in  spite  of  the  fact  that  the  effector 
is  now  more  diversified.  As  an  example  of  this  kind  of  response  might  be  men- 
tioned the  patellar  reflex.  The  stimulus  is  applied  to  the  patellar  ligament  whence 
the  impulse  is  transferred  to  the  sciatic  center  by  way  of  the  afferent  fibers  of  this 
nerve.  It  attains  the  muscles  upon  the  anterior  aspect  of  the  thigh  by  waj^  of 
the  efferent  fibers  of  the  same  nerve  (ant.  crural  nerve). 

(c)  Spreading  reflexes,  in  which  a  large  number  of  motor  organs  are  involved. 
Thus,  a  certain  stimulus  may  lead  to  the  contraction  of  many  muscles  far  removed 
from  one  another.      Their  action,  however,  remains  co-ordinated. 

{d)  Antagonistic  reflexes  are  made  possible  by  the  so-called  reciprocal  innerva- 
tion, first  described  by  Sherrington.  ^  It  frequently  happens  that  the  reflex  activa- 
tion of  a  certain  muscle  causes  at  the  same  time  a  lessening  of  the  tonus  of  the  cor- 
responding antagonistic  muscle.  In  a  similar  way,  the  relaxation  of  a  previously 
contracted  muscle  very  frequently  incites  a  contraction  of  the  relaxed  antagonistic 
muscle.  This  phenomenon  is  most  clearly  displayed  by  the  flexors  and  extensors 
of  the  arms  and  legs,  and  also  by  the  constrictors  and  dilators  of  the  iris  and  other 
reciprocating  effectors.  It  seems,  however,  that  this  reciprocity  is  not  dependent 
upon  a  paired  arrangement  of  the  peripheral  nerves,  but  upon  a  peculiar  adjustment 
of  the  motor  centers  governing  the  action  of  these  antagonistic  muscles.-  Appar- 
ently, their  connection  is  such  that  the  excitation  of  one  motor  cell  causes  the 
activity  of  the  other  to  be  inhibited. 

(e)  Tonic  and  Spastic  Reflexes. — The  reaction  following  a  certain  stimulus  is 
usually  prolonged,  and  lasts  much  longer  than  the  stimulus.  In  manj''  cases,  in 
fact,  it  assumes  so  continuous  a  character  that  it  may  be  characterized  as  a  true 
reflex  spasm.  Experimentally,  this  peculiarity  may  be  imparted  to  reflexes  very 
easily  by  the  administration  of  small  doses  of  strychnin  or  morphin.  It  is  also  a 
frequent  symptom  of  certain  pathologic  conditions  tending  to  augment  the  ir- 
ritability of  the  nervous  system.  A  not  uncommon  reflex  of  this  type  is  the  condi- 
tion known  as  blepharospasm,  a  tonic  spasm  of  the  ej'elids. 

(/)  Periodic  and  Clonic  Reflexes. — In  many  instances  a  stimulus  may  cause  a 
certain  response  to  be  repeated  a  number  of  times  at  regular  inter\-als.  This  is 
true  of  the  acts  of  sneezing,  coughing,  hiccoughing,  swallowing,  the  clattering  of 
the  teeth,  and  trembling.  The  cremasteric  reflex  also  consists  of  an  often  repeated 
raising  and  lowering  of  the  testicle.  The  same  is  true  of  the  scratching  reflex,  and 
of  those  which  may  be  elicited  in  decerebrated  cats  and  dogs  by  tickling  the  lateral 
aspect  of  the  abdomen.  In  many  cases,  these  reactions  recur  at  very  brief  intervals 
and  assume  a  prolonged  or  clonic  character.  Of  especial  clinical  importance  is  the 
ankle  clonus,  a  periodic  reflex  which  may  be  set  up  by  suddenly  flexing  the  foot 
and  stretching  the  tendo  Achillis.  In  certain  nervous  diseases  even  the  patellar 
reflex  may  assume  a  clonic  character. 

(g)  Alternating  reflexes  are  commonly  produced  by  an  alternating  activity  of 
antagonistic  groups  of  muscles.  Instead  of  one  reaction,  a  number  of  them  are 
obtained  in  orderly  sequence.  The  rocking  back  and  forth  of  the  head  upon  the 
trunk  may  be  cited  as  an  example  of  this  type  of  reflex.  In  decerebrated  animals 
certain  stimuli  produce  at  times  an  alternate  flexion  and  extension  (kicking)  of  the 
two  posterior  extremities. 

(h)  Association  or  Perception  Reflexes. — It  has  previously  been  stated  that  the 
differential  sign  between  a  reflex  and  a  reaction  is  volition.  Attention  has  also 
been  called  to  the  fact  that  a  relatively  small  number  of  reflexes  necessitate  an  im- 
pression in  consciousness,  otherwise,  they  cannot  fully  develop.  These  actions 
which  skirt  the  realm  of  volition  without  being  actually  influenced  by  it,  are  desig- 

1  The  Integrative  Action  of  the  Nerve  System,  Liverpool,  1906. 

2  Ewald,  Pfliiger's  Archiv,  .xciv,  1903,  46 


KKFI.KX    ACTION  593 

natod  as  perception  or  associalion  reflexes.  Thus,  the  flow  of  saliva  or  ^aslric 
juiee  may  he  eliciteil  upon  Kainiujr  a  visual  or  olfactory  concept  of  well-cooked  food. 
Quite  similarly,  the  yawning  reflex  nuiy  i)e  evoked  in  us  in  conseeiueruie  of  a  visual 
imi)ression  of  some  one  else  already  cnKaj>;ed  in  this  act;  or  we  may  receive  stimuli 
tendinp;  to  produce  micturition  at  the  .sinht  or  sound  of  runniiif;  water.  To  this 
;;roup  also  heloiiKS  the  act  of  vomiting  at  the  si^ht  of  foul  food,  as  well  as  the  .so- 
called  idioinotor  nio\einents.  The  latter  consist  in  involuntary  movements 
executed  by  us  in  imitation  of  the  position  of  other  people.  Thus,  we  may  follow 
the  movements  of  a  football  player  and  find  ourselves  eventually  in  a  state  of 
muscular  contraction  without  actually  realizing  how  we  got  into  it. 

38 


SECTION  XV 
THE  FUNCTION  OF  THE  SPINAL  CORD 


CHAPTER  XLIX 


THE  SPINAL  CORD  AS  A  REFLEX  CENTER— ITS  POWER  OF 

AUTOMATICITY 

Localization  of  the  Spinal  Reflex  Centers. — While  it  is  true  that 
the  segment alism  so  clearlj'  betrayed  by  the  lower  forms,  is  also  in 
evidence  in  the  mammals,  it  must  be  admitted  that  it  has  lost  much 
of  its  original  conspicuousness  on  account  of  the  development  of  the 
long  conducting  system  and  of  those  central  complexes  of  neurons 
which  give  rise  to  psychic  and  other  singular  activities.  In  endeavor- 
ing to  compare  the  conditions  found  in  a  tj^pical  segmental  or  reflex 
animal,  such  as  the  crayfish,  with  those  existing  in  man,  it  may  be 
advantageous  to  begin  this  discussion  with  a  general  survey  of  the 
structural  and  functional  arrangement  of  the  spinal  paths  in  the 
intermediate  groups  of  animals  formed  by  the  reptilia  and  amphibia. 
We  have  previously  noted  that  a  stimulus  applied  to  the  foot  of  a 
decerebrated  frog,  eventual!}'  induces  muscular  contractions  which 
lead  to  a  retraction  of  the  leg  from  the  seat  of  the  stimulation  (Tiirck's 
method).  If  the  spinal  cord  is  now  thoroughly  destroyed  with  the 
aid  of  a  thin  wire,  it  will  be  found  that  subsequent  to  this  time  the 
stimulus  remains  absoluteh-  ineffective.  This  result  proves  that 
the  destruction  of  the  spinal  cord  has  produced  in  this  case  a  break 
in  the  circuit  of  this  particular  reflex.  Secondly,  as  the  receptor  and 
effector,  as  well  as  the  afferent  and  efferent  paths,  have  not  been  in- 
terfered with  in  this  instance,  the  aforesaid  procedure  must  have  led 
to  a  destruction  of  the  center  necessary  for  this  reflex.  Thirdly, 
inasmuch  as  all  other  reflexes  occurring  in  the  realm  of  the  spinal 
cord,  have  also  been  abolished,  the  deduction  may  justly  be  made 
that  this  part  of  the  nervous  system  contains  the  centers  for  a  large 
number  of  reflex  circuits  and  may,  therefore,  be  regarded  as  an  impor- 
tant seat  of  reflex  action. 

We  have  thus  established  one  of  the  two  most  important  functions 
of  the  spinal  cord,  the  other  being  its  power  of  conduction  by  means 
of  which  the  actions  of  peripheral  parts  are  correlated  with  those  of  the 
cerebrum  and  allied  structures.  It  is  probably  not  necessary  to  remind 
the  student  of  the  fact  that  the  destruction  of  this  part  of  the  nervous 
system  does  not  abohsh  all  reflex  action.     Only  those  reflexes  are 

594 


THE    SPINAL    CORD    AS    A    REFLEX    ("ENTP:r 


595 


destroyed  by  this  procedure  which  are  nornuilly  iiietliated  by  the 
spinal  cord.  Thus,  the  large  number  of  s^'uipatiietic  responses 
continue  even  in  tlu^  absence  of  the  cord  and  the  sanu;  holds  tru(?  of 
those  accomplished  with  the  help  of  th(;  cranial  nerves,  provided,  of 
course,  that  the  region  of  the  medulla  oblongata  has  been  left  intact. 

In  the  frog,  the  spinal  cord  extends  backward  as  far  as  the  ninth 
vertebra,  namely,  to  the  prominence  upon  the  dorsal  aspect  of  its 
body.  The  tenth  vertebra,  or  urostyle,  continues  onward  from  here 
and  forms  the  dorsal  wall  of  the  long  extended  ab- 
domen and  pelvis.  By  cutting  transversely  across 
the  cord,  beginning  at  the  level  of  the  first  vetebra, 
it  is  possible  to  show  that  the  reflexes  from  the 
hind  limbs  are  not  aboUshed  until  the  level  of  the 
cartilage  between  the  sixth  and  seventh  vertebrae 
has  been  reached.  Any  section  distally  to  this 
point  of  the  cord  destroys  the  aforesaid  reflexes 
immediately.  The  conclusion  must,  therefore,  be 
made  that  the  reflex  center  for  the  hind  limbs  is 
situated  opposite  to  the  seventh  and  eighth  verte- 
brae (Fig.  294).  It  is  generally  designated  as  the 
"sciatic  center,"  because  the  paths  which  connect 
it  with  the  periphery  are  collected  on  each  side  in 
one  bundle,  known  as  the  sciatic  nerve.  The  latter 
arises  by  three  roots  and  it  can  be  shown  by  stimu- 
lation with  weak  electrical  currents  that  these 
radicles  possess  a  somewhat  different  function,  be- 
cause they  innervate  different  groups  of  muscles 
and  thus  give  rise  to  several  specific  movements 
of  the  leg.  With  the  aid  of  very  delicate  electrodes, 
it  can  also  be  proved  that  a  similar  localization  of 
function  is  present  in  the  sciatic  center  itself. 

This  method  of  dividing  the  spinal  cord  at 
different  levels  has  also  proved  that  the  centers  for 
the  muscles  of  the  abdomen  are  situated  anteriorly 
to  the  sciatic  center  and  that  the  center  for  the  fore 
limbs  is  located  anteriorly  to  these.  Several  reflex 
and  automatic  centers  are  also  found  in  the  me- 
dulla oblongata,  namely,  those  controlling  the  car- 
diac, respiratory  and  vasomotor  activities.  It  is  evident,  therefore, 
that  the  spinal  cord  of  the  frog  and  allied  animals  contains  a  series  of 
centers  for  simple  reflex  action  and  that  a  segmentalism  exists  in 
these  animals  which  closely  approaches  that  found  in  the  vermes  and 
crustaceae. 

Spinal  Reflexes  in  the  Mammals. — If  the  attempt  is  made  to 
pursue  similar  methods  of  localization  in  the  mammals,  we  are 
immediately  confronted  by  several  difficulties,  one  of  which  is 
the   much   greater   susceptibility   and   sensitiveness   of   the   nervous 


Fig.  294.— Dia- 
graji  to  show  the 
Position  of  the  Re- 
flex Centers  in  the 
Spinal  Cord  of  the 
Frog. 

BC    and    BN, 

Brachial  center  and 
nerve;  A,  center  for 
the  parts  of  the 
trunk;  SC  and  SN, 
sciatic  center  and 
nerv'e.  The  num- 
bers indicate  the 
different  vertebrae. 


596  THE    FUNCTION    OF   THE    SPINAL   CORD 

system  of  these  animals  to  operative  interferences.  The  profound 
general  reactions  following  these  operations,  are  commonly  centered  in 
the  phenomenon  of  shock  and  the  development  of  a  hypersensitiveness 
which  frequently  overshadows  the  primary  effect.  But  while  it  must 
be  granted  that  the  spinal  cord  of  the  higher  animals  does  not  exhibit 
quite  so  decided  a  segmentalism  as  that  of  the  reptiles,  amphibia  and 
fish,  it  nevertheless  evinces  a  decided  tendency  at  locahzation  of  func- 
tion. Sherrington,!  for  example,  has  shown  that  the  decapitated  cat 
reacts  to  stimulations  of  the  skin  either  by  scratching  movements  or 
by  flexion  and  extimsion  of  the  legs.  In  fact,  it  is  easily  noted  that  a 
decerebrated  animal,  or  one  in  which  merely  a  part  of  the  cerebral 
cortex  has  been  removed,  exhibits  an  even  greater  number  of  reflexes 
than  a  normal  animal.  Quite  similarly,  the  division  of  the  spinal 
cord  at  a  point  posterior  to  the  nuclei  of  the  phrenic  nerves  does  not 
materially  affect  the  reflexes  from  the  posterior  extremities.  The 
patellar  and  other  deep  reflexes  are  not  destroyed  thereby. 

Besides  these  centers  which  are  solely  concerned  with  reactions 
of  skeletal  muscle,  it  has  been  proved  that  the  spinal  cord  also  con- 
tains centers  for  several  reflex  acts  of  different  character,  as  follows: 

(a)  Dilatation  of  the  pupil.  This  center  lies  opposite  the  1.-3.  thoracic  ver- 
tebrae. The  motor  fibers  leave  by  the  anterior  roots  and  enter  the  upper  thoracic 
nerves  and  the  cervical  sympathetic,  terminating  finally  in  the  ganglion  cervicale 
superior. 

(b)  The  center  for  defecation,  or  centrum  anospinale,  is  situated  opposite 
the  fifth  lumbar  vertebra  (dog).  The  afferent  path  is  formed  by  the  plexus 
hemorrhoidalis  and  the  efferent  path  by  the  nervus  hypogastricus. 

(c)  The  center  for  micturition,  or  centrum  vesicospinale,  is  situated  in  the 
lumbar  or  sacral  segment  of  the  spinal  cord.  The  nervi  hypogastrici  and  erigentes 
constitute  the  efferent  path. 

(d)  The  centers  for  the  erection  of  the  male  and  female  generative  organs  are 
situated  in  the  lumbar  portion  of  the  cord.  The  arteria  profunda  penis  is  inner- 
vated by  the  vasomotor  fibers  of  the  1.-3.  sacral  nerves,  while  the  3.  and  4.  sacral 
nerves  activate  the  muse,  ischiocavernosus  and  transversus  perinei  profundus. 

(e)  The  center  for  ejaculation  is  also  placed  in  the  lumbar  segment  of  the 
cord. 

(f)  The  center  for  the  contraction  of  the  uterus  is  located  in  the  lumbar  seg- 
ment of  the  cord. 

(g)  The  centers  in  the  bulbar  enlargement  of  the  cord,  i.e.,  in  the  medulla 
oblongata,  regulate  the  activity  of  the  heart,  the  respiratory  movements,  the  cali- 
ber of  the  blood-vessels,  deglutition,  reversed  deglutition  or  vomiting,  heat  dissi- 
pation, and  other  functions. 

In  view  of  this  rather  well  marked  segmentalism,  it  cannot  be 
denied  that  the  spinal  cord  of  the  higher  animals  possesses  a  functional 
arrangement  very  similar  to  that  present  in  the  lower  forms.  It  is  an 
important  seat  of  reflex  action.  But,  inasmuch  as  the  cerebrum  gradu- 
ally gains  a  more  complete  control  over  these  simple  functions, 
the  spinal  centers  lose  their  independency  of  action.  This  is  especiafly 
true  of  man,  because,  somewhat  contrary  to  the  results  obtained  in  the 
dog,  cat  and  rabbit,  the  complete  division  of  the  spinal  cord  is  followed 
1  Jour,  of  Physiol.,  xxxviii,  1909,  375. 


THE    SPINAL    COKD    AS    A    KEFLEX    CENTER  597 

in  this  case  by  an  abolition  of  the  n^licxcs  and  a  n^'iicral  loss  of  irrita- 
bility of  the  nervous  structures  situated  posterior  to  the  cut.'  A 
partial  division  of  the  cord,  however,  is  often  recovered  from  without 
permanent  loss  of  function. 

In  this  connection,  brief  reference  should  also  be  niadc;  to  the  ex- 
periments of  Cioltz,'-'  purposing  to  arrive  at  a  definite  conclusion  rc- 
fi;arding  the  function  of  the  spinal  cord  by  the  method  of  total  or  partial 
extirpation.  In  the  mammals,  the  former  procedure  is  not  feasible, 
for  the  reason  that  the  phrenic  nerves  take  their  origin  from  its  cervical 
portion.  Any  interference  with  the  phrenic  nuclei  would  cause  a 
stoppage  of  the  respiratory  movements.  Goltz,  therefore,  removed  the 
cord  merely  as  far  as  its  upper  thoracic  segment,  special  care  being 
taken  to  protect  these  animals  against  an  undue  loss  of  heat  and  other 
injurious  influences.  Those  surviving  the  operation,  showed  a  com- 
plete motor  paralysis  which  eventually  gave  way  to  an  atrophic  condi- 
tion of  tlu^se  parts.  They  also  exhibited  a  complet{^  sensory  anesth(!sia, 
and  although  their  vasomotor  and  other  autonomic  functions  remained 
depressed  for  some  time  after  the  operation,  the  vascular  tonus  re- 
appeared in  a  large  measure.  In  addition  it  was  noted  that  the 
ordinary  pelvic  reflexes  again  assumed  their  original  (juahtics.  These 
results  indicate  very  clearly  that  the  sympathetic  system  is  relatively 
independent  of  the  spinal  cord  and  other  parts  of  the  central  nervous 
system,  because  the  digestive,  secretory,  circulatory  and  excretory 
organs  eventually  regained  their  functions  after  the  destruction  of  the 
cord.  Various  other  symptoms,  however,  such  as  a  gradual  lowering 
of  the  body  temperature  and  a  very  decided  loss  of  adaptation  of  the 
parts  formerly  innervated  by  the  destroyed  portion  of  the  cord,  sug- 
gested that  the  animal  was  no  longer  able  to  influence  its  autonomic 
organs  and  to  correlate  their  functions  with  those  of  other  structures. 

The  Automatic  Activity  of  the  Spinal  Cord. — Having  established 
the  fact  that  the  spinal  cord  is  an  important  seat  of  reflex  action,  it 
should  be  noted  that  several  of  the  centers  situated  within  the  domain 
of  the  cord  and  bulb,  are  automatically  active.  Admittedly,  an  auto- 
matic action  finds  its  origin  neither  in  volition  nor  in  sensory  impres- 
sions of  the  ordinary  intermittent  type.  Its  cause  must  rather  be 
sought  in  an  "inner"  stimulus  which  arises  in  consequence  of  constant 
and  specific  stimulations  and  renders  the  center  self-inducing.  The 
question  of  whether  the  centers  of  the  spinal  cord  possess  automatic 
qualities,  must  be  answered  in  the  positive  and  especially  if  the  medulla 
oblongata  is  taken  to  be  a  part  of  this  structure.  Thus,  it  is  a  well 
known  fact  that  the  cardiac,  respiratory  and  vasomotor  centers  are 
composed  of  cellular  elements  which  generate  impulses  rhythmically 
in  consequence  of  inherent  stimuli.  While  it  is  entirely  probable  that 
the  centers  situated  in  the  more  posterior  segments  of  the  cord 
possess  a  much  slighter  automatic  power  than  those  just  mentioned, 
it  must  nevertheless  be  admitted  that  they  generate  impulses  at  regular 

1  Collier,  Brain,  1904,  38. 

2  pfliiger's  Archiv,  Ixviii,  1896,  362. 


598  THE    FUNCTION    OF    THE    SPINAL    CORD 

intervals.  Moreover,  as  these  impulses  are  intended  merely  to  produce 
a  tonic  setting  of  the  peripheral  musculature,  the  aforesaid  spinal 
centers  may  be  said  to  be  tonically  automatic,  in  contradistinction 
to  the  bulbar  centers,  which  may  be  considered  as  being  rhythmically 
automatic. 

It  must  be  admitted,  therefore,  that  the  ganglion  cells  composing 
these  centers  are  in  a  state  of  constant  tonic  activity.  This  implies 
that  they  produce  "subthreshold"  impulses  at  regular  intervals 
which  tend  to  retain  the  effector  in  a  condition  of  functional  alertness 
ready  at  any  time  to  yield  maximal  effects.  Conversely,  it  may  be 
concluded  that  the  loss  of  these  impulses  must  diminish  the  tonus 
of  the  effector  and  induce  atrophic  changes.  You  will  have  noticed 
that  the  legs  of  a  decerebrated  frog,  suspended  from  a  hook,  assume  a 
definite  position  of  flexion,  because  the  muscles  are  still  in  connection 
with  the  motor  cells  of  the  cord.  If  one  of  the  sciatic  nerves  is  now 
cut,  the  muscles  on  the  side  of  the  lesion  immediately  relax  and  allow 
the  leg  as  a  whole  to  assume  a  more  dependent  position.  In  view  of 
the  fact  that  these  changes  cannot  be  observed  in  a  reflex  frog  after  the 
skin  has  been  removed  or  after  the  posterior  roots  of  the  spinal  cord 
have  been  divided,  it  has  been  assumed  that  the  tonic  automaticity  of 
the  spinal  ganglion  cells  is  due  to  a  constant  influx  of  subminimal 
sensory  impulses  from  the  cutaneous  receptors.  In  other  words,  it 
is  assumed  that  the  "inner  stimulus"  imparted  to  the  motor  cells  of 
the  cord,  finds  its  origin  in  sensory  impulses  of  such  slight  intensity 
that  they  cannot  incite  muscular  contraction.  Hence,  the  tonus 
of  a  muscle  is  really  a  subminimal  reflex  phenomenon.  The  inherent 
or  inner  stimulus  upon  which  the  automatic  power  of  a  nerve  cell 
depends,  may  thus  be  referred  to  subminimal  sensory  stimuli. 

Superficial,  Deep,  and  Organic  Reflexes. — In  man,  the  spinal 
cord  aids  in  the  production  of  a  number  of  reflexes  which  possess  a 
very  distinctive  character  and  may  on  this  account  be  employed  for 
purposes  of  diagnosis.  Among  the  superficial  or  skin  reflexes  may  be 
mentioned  the: 

(a)  Cremasteric  Reflex. — This  reaction  is  elicited  best  by  gently  rubbing  across 
the  inner  aspect  of  the  thigh.  It  consists  in  a  raising  of  the  scrotal  sac  and  testicle 
in  consequence  of  the  contraction  of  the  muse,  cremaster. 

(6)  Scrotal  Reflex. — It  presents  itself  as  a  contraction  of  the  tunica  dartos  in 
consequence  of  an  excitation  applied  to  the  skin  of  the  scrotum. 

(c)  Sternal  and  Abdominal  Reflexes. — These  reactions  may  be  evoked  by  rapidly 
drawing  the  blunt  end  of  a  rod-like  instrument  across  the  external  surface  of  the 
chest  or  abdominal  wall.     It  consists  in  a  contraction  of  the  neighboring  muscles. 

((/)  Scapular  Reflex. — It  results  in  consequence  of  excitations  of  the  skin  in 
the  vicinity  of  the  spinal  column.     The  muse,  rhomboidei  contract. 

(e)  Pharijngeal  Reflex.~The  touching  of  the  posterior  wall  of  the  pharynx 
incites  a  contraction  of  the  muscles  lining  this  passage. 

(/)  Mammillarij  Reflex. — The  stimulation  of  the  integument  in  the  vicinity  of  the 
nipple  is  followed  by  an  erection  of  the  papilla. 

{§)  Ghtteal  Reflex. — The  muse,  gluteus  maximus  contracts  in  consequence  of 
stimuli  applied  to  the  skin  covering  the  buttocks. 


THE  SPINAL  CORD  AS  A  REFLEX  CENTER         599 

(h)  Plantar  Reflex. — It  consists  in  a  flexion  of  tho  toes  in  consequence  of  tactile 
stimulation  of  the  sole  of  the  foot.  In  certain  alTcctions  of  the  pyramidal  tracts 
of  the  cord,  this  stimulation  elicits  an  extension  of  the  great  toe,  instead  of  a  flexion. 
This  constitutes  tlu;  so-called  Hal)inski  phenomenon. 

(i)  Bnlhocavernoauii  Reflex. — This  muscle  may  be  made  to  react  to  stimuli 
applied  to  the  glans  penis. 

0)  Reflexes  from  the  mucosa  may  be  elicited  by  stimulation  of  dilTerent  mucous 
surfaces. 

(A;)  Winking  Reflex. — The  eyelids  are  closed  if  a  stimulus  is  applied  either 
to  the  cornea,  conjunctival  mcml)rane  or  .skin  covering  the  eyelids. 

(/)  Reflexes  from  the  Facial  Muscles. — These  responses  are  obtained  by  stimu- 
lating the  skin  in  vicinity  of  these  muscles. 

Among  the  so-called  deep  reflexes,  i.e.,  reflexes  which  are  elicited  by  stimula- 
tions of  the  tendons,  ligaments  and  periosteum,  may  be  mentioned  the: 

(a)  Patellar  Reflex  or  Knee-jerk.^ — A  slight  stroke  upon  the  ligamentum  patella? 
produces  a  contraction  of  the  muse,  quadriceps  femoris,  involving  especially  the 
muse,  vastus  medialis  and  vastus  intermedius.  The  best  results  are  obtained  if 
the  muscle  is  first  put  under  a  slight  tension  which  end  can  readily  be  attained  by 
crossing  the  knees  or  by  sitting  upon  a  chair  or  table  and  permittiag  the  leg  to 
hang  free  across  its  edge. 

(6)  Achillis  Jerk. — If  the  foot  is  placed  in  the  position  of  dorsiflexion,  a  tap 
upon  the  tendo  calcaneus  (Achillis)  evokes  a  contraction  of  the  muse,  gastrocne- 
mius and  plantar  flexion  of  the  foot.  The  so-called  ankle  clonus  is  obtained  if 
the  foot  is  quickly  flexed  so  that  the  tendo  Achillis  and  muse,  gastrocnemius  are 
suddenly  stretched.  •  In  certain  nervous  disorders  this  reaction  acquires  a  periodic 
character. 

(c)  Wrist  Jerk. — This  reflex  is  obtained  by  tapping  the  tendons  of  the  muscles 
of  the  forearm.  Similar  effects  are  yielded  by  the  muse,  gracilis,  semitendinosus, 
triceps  and  biceps. 

(d)  Jaw  Jerk. — The  jaws  are  closed  if  the  lower  jaw  is  tapped  when  in  the 
half -open  position. 

(e)  Periosteal  Reflexes. — The  muse,  supinator  longus  and  biceps  contract  if  the 
head  of  the  radius  is  tapped  upon. 

(/)  Tensor  Tympani  Reflex. — The  muse,  tensor  tympani  contracts  as  a  result  of 
sound  impacts  of  high  pitch.     The  ear  drum  is  in  this  way  rendered  more  tense. 

The  organic  or  visceral  reflexes  have  been  enumerated  in  part  above.  They 
include  those  pertaining  to  micturition,  defecation  and  the  sexual  activities.  They 
are  executed  chiefly  with  the  help  of  smooth  muscle  and  glandular  tissue,  while 
the  superficial  and  deep  reflexes  are  largely  concerned  with  striated  muscle. 

The  Nature  of  the  Patellar  Reflex. — While  the  question  whether 
or  no  the  knee-jerk  is  a  true  reflex,  has  been  decided  in  favor  of  the 
first  view,  this  decision  has  not  been  reached  without  considerable 
discussion.  To  begin  with,  it  was  thought  that  it  could  not  be  a 
true  reflex,  because  the  time  interposed  between  the  stroke  upon  the 
patella  and  the  contraction  of  the  muse,  quadriceps,  is  altogether 
too  short  to  permit  of  the  passage  of  the  impulse  through  the  spinal 
cord.  This  view  was  based  upon  the  early  calculations  of  the  speed 
of  the  nerve  impulse  which,  in  accordance  with  Helmholtz,  amounts 
to  33  m.  in  a  second  in  warm-blooded  animals.  It  was  believed, 
therefore,  that  the  sensory  impulse  does  not  enter  the  spinal  center 
at  all,  but  is  transferred  to  the  muscle  by  way  of  a  peripheral  collateral. 
If  this  conception  were  correct,  the  patellar  reflex  should  really  be 

^  Discovered  by  Erb,  Archiv  fur  Psychiatric,  v.  1875;  and  Westphal,  ibid.,  1875. 


600  THE    FUNCTION    OF   THE    SPINAL    CORD 

regarded  as  a  pseudo  or  axone  reflex,  i.e.,  as  one  which  is  had  without 
the  intervention  of  the  cell-body  or  center.  In  other  words,  the  im- 
pulse set  up  in  the  receptor,  passes  no  farther  than  the  next  collateral, 
where  it  finds  a  direct  course  to  the  effector.  This  explanation, 
as  has  just  been  stated,  was  intended  to  bring  the  extremely  brief  time 
of  the  patellar  reflex  into  relation  with  the  speed  of  the  nerve  impulse, 
as  determined  by  the  older  methods.  Applegarth,  for  example, has 
stated  that  the  patellar  reflex  time  is  0.014-0.02  sec.  (dog),  while 
Waller  and  Gotch  found  it  to  be  0.008-0.005  sec.  (rabbit).  Later  on, 
however,  it  has  been  shown  by  means  of  the  string  galvanometer, 
that  the  speed  of  the  nei-ve  impulse  in  warm-blooded  animals  may 
amount  to  more  than  100  m.  in  a  second.  In  addition,  Snyder^  and 
Hoffmann-  have  ascertained  that  the  patellar  reflex  time  lies  somewhere 
between  0.0113  and  0.024  sec.  These  figures,  therefore,  prove  very 
conclusively  that  the  patellar  reflex  must  involve  the  spinal  center; 
at  least,  the  time  allowed  for  it  is  sufficient  to  complete  the  entire 
circuit  from  the  hgament  to  the  cord  and  back  again  to  the  muscle. 

The  objection  has  also  been  raised  that  the  contraction  of  the 
muse,  quadriceps  is  a  simple  twitch  and  not  a  tetanus,  as  is  usually 
the  case  when  muscles  are  activated  reflexly.  Much  has  also  been 
made  of  the  fact  that  the  aforesaid  muscle  reacts  best  when  subjected 
to  a  slight  tension.  It  has  been  found,  however,  that  not  all  muscular 
responses  are  tetanic  in  their  character.  Sherrington,-^  for  example, 
has  called  attention  to  the  fact  that  the  so-called  ''extensor  thrust" 
which  may  be  obtained  in  animals  by  suddenly  pressing  upon  the 
plantar  surface  of  the  hind  foot,  consists  of  simple  contractions  of  the 
extensor  muscles  of  the  hind  leg.  Lastly,  it  has  been  proved  that 
any  injury  to  the  lumbar  segment  of  the  spinal  cord  destroys  the 
patellar  reflex  and  that  its  abolition  may  also  be  effected  by  dividing 
either  the  posterior  or  the  anterior  roots  of  the  cord.  Obviously, 
therefore,  the  production  of  the  patellar  reflex  necessitates  not  only 
an  intact  spinal  center  but  also  intact  centripetal  and  centrifugal 
paths.  Its  reflex  nature,  therefore,  seems  to  be  thoroughl}^  established. 
A  similar  controversy  has  led  to  the  establishment  of  the  fact  that  the 
Achillis  jerk  is  a  true  reflex. 

Reinforcement  of  Reflexes."* — In  testing  the  different  reflexes,  it 
soon  becomes  apparent  that  the  subject  must  remain  in  a  state  of  perfect 
inattentioti,  otherwise  the  response  will  be  less  intense,  or  may,  in 
fact,  be  entirely  abolished.  In  other  words,  if  the  attention  of  the 
subject  is  directed  to  the  procedure  of  eliciting  the  reflex,  the  usual 
result  is  its  inhibition  by  the  cerebral  centers.  In  this  way,  a  diagnosis 
of  abolition  of  reflexes  may  be  made  which  in  reality  is  nothing  more 
than  a  normal  phenomenon.     This  difficulty  may  be  easily  overcome 

1  Am.  Jour,  of  Physiol.,  xxvi,  1910,  474. 

2  Archiv  fiir  Physiol.,  1910,  223. 

3  Jour,  of  Physiol.,  xxxviii,  1909,  375. 

*  First  observed  by  Jendrassik  in  1883. 


THE    SPINAL    CORD    AS    A    REFLEX    CENTER  GOl 

if  tho  subject  is  askod  to  ongap;o  in  some  mental  proc(^ss  while  the 
stimulus  is  brouji;lit  to  bear  upon  his  intep;ument  or  tendons.  The 
reflexes  may  also  be  augmented  by  asking  the  subject  to  make  a  voli- 
tional muscular  effort  at  tho  time  the  blow  is  struck.  This  requires  a 
certain  mental  concept  and  it  is  conceivable  that  the  activation  of  th(! 
cerebrum  temporarily  abolislu^s  its  inhibitory  power,  and  thus  dimin- 
ishes the  resistance  along  the  different  reflex  circuits.  Under  ordinary 
conditions,  the  patellar  reflex  may  be  heightened  very  materially  by 
simultaneously  contracting  the  muscles  of  the  hands  or  by  endeavoring 
to  pull  the  interlocked  fingers  apart.  But,  while  we  are  able  in  this 
way  to  intensify  a  feeble  jerk,  no  effect  can  be  produced  after  the  reflex 
has  been  aboUshed  by  disease. 

This  phenomenon  which  is  usually  described  as  reinforcement  of 
reflexes,^  also  permits  of  a  second  explanation.  It  is  commonly 
recognized  that  the  functional  activity  of  one  part  of  the  nervous 
system  also  influences  the  irritability  of  others.  Thus,  it  may  rightly  be 
assumed  that  the  activation  of  the  cerebrum,  accompanying  such 
actions  as  the  interlocking  of  the  hands  or  fingers,  renders  this  organ 
more  irritable.  The  motor  impulses  thus  generated  in  its  cortical 
area,  escape  through  the  descending  columns  of  the  cord,  where  they 
skip  to  neighboring  columns  and  nuclei  and  give  rise  to  a  general 
activity  of  these  nervous  elements.  In  other  words,  the  constituents 
of  the  spinal  reflex  circuits  are  sensitized  by  an  overflow  of  the  cerebral 
impulses.  It  is  quite  impossible  at  this  time  to  decide  definitely 
which  of  these  two  theories  is  the  more  correct.  Obviously,  the  first 
more  closely  agrees  with  the  common  phenomenon  of  inhibition  of 
reflexes  by  the  cerebral  centers,  while  the  second  introduces  a  rather 
new  factor  in  the  form  of  an  activation  of  certain  parts  of  the  nervous 
system  which  He  at  some  distance  from  the  seat  of  the  primary  process. 

It  should  also  be  noted  that  the  reinforcement  does  not  develop 
if  the  interval  of  time  between  the  simultaneous  effort  and  the  excita- 
tion is  too  long.  Thus,  it  has  been  shown  by  Bowditch  and  "Warren  ^ 
that  the  knee-jerk  suffers  its  greatest  augmentation  if  the  blow  upon 
the  tendon  precedes  the  reinforcing  action  by  less  than  0.6  to  0.9 
sec.  A  greater  interval  will  tend  to  minimize  the  reinforcement  until 
it  eventually  gives  way  to  an  inhibition.  This  diminution  of  the  reflex 
in  consequence  of  a  premature  simultaneous  effort  is  designated  as 
negative  reinforcement. 

AboUtion  and  Exaggeration  of  the  Reflexes. — With  few  exceptions, 
reflexes  may  be  regarded  as  a  safe  index  of  the  relative  state  of  irrita- 
biUty  of  the  nervous  system,  provided,  of  course,  that  the  method  of 
stimulation  is  free  from  error.  But  even  a  perfectly  normal  body 
undergoes  diurnal  and  seasonal  changes  which  reflect  their  influences 
upon  reflexes.  Thus,  we  find  that  they  are  weakened  during  sleep  and 
other  states  of  mental  rest;  in  fact,  some  of  them  are  aboHshed  entirely 

'  Mitchell  and  Lewis,  Am.  Jour,  of  the  Med.  Sciences,  xlii,  1886,  363. 
2  Jour,  of  Phy.siol.,  ii,  1890,  25. 


602  THE    FUNCTION    OF    THE    SPINAL    CORD 

during  these  periods.  Conditions  of  mental  excitement  and  general 
neurasthenia,  on  the  other  hand,  increase  them  very  markedly. 

While  one  or  the  other  of  the  reflexes  enumerated  previously  may 
be  absent  in  a  perfectly  healthy  person,  their  general  abolition  sug- 
gests in  most  cases  a  pathological  lesion  of  some  kind.  This  defect 
may  be  restricted  to  a  particular  reflex  circuit  or  may  involve  more 
extensive  areas  of  the  nervous  system.  In  the  first  instance,  the  break 
must  have  occurred  at  some  point  of  the  reflex  arc  which  now  fails  to 
respond  even  on  reinforcement,  while,  in  the  second  instance,  a  more 
general  or  central  depression  of  the  nervous  system  must  have  re- 
sulted. In  illustration  of  the  first  condition  might  be  mentioned  the 
loss  of  a  particular  superficial  or  deep  reflex  of  the  spinal  cord  in  con- 
sequence of  acute  anterior  poliomyelitis  which  infection  destroys 
the  motor  cells  in  the  anterior  horn  of  the  gray  matter.  Reference 
might  also  be  made  to  tabes  dorsalis  in  which  affection  the  posterior 
root  terminals  in  the  cord  are  destroyed,  thereby  causing  a  break  in  the 
central  distribution  of  the  analyzer.  Among  the  general  depressions 
of  the  nervous  system  producing  diminution  or  abolition  of  the  spinal 
and  other  reflexes,  might  be  mentioned  increases  in  intracranial  pres- 
sure, such  as  result  in  hydrocephalus  or  in  consequence  of  cerebral 
tumors.  They  are  also  abolished  for  a  time  in  comas  and  epileptic 
seizures  and  certain  febrile  reactions,  such  as  pneumonia. 

Reflexes  are  said  to  be  exaggerated  when  the  slightest  possible 
stimulus  elicits  an  unusually  brisk  motor  response.  This  is  a  common 
phenomenon  in  simple  neurasthenia  and  hysteria  and  other  conditions 
in  which  the  irritability  of  the  nervous  system  has  been  increased  in 
consequence  of  the  absorption  of  various  poisons,  such  as  the  products 
of  intestinal  fermentation,  strychnin,  caffein,  thebein,  and  others.  In 
many  cases  the  reflexes  are  then  augmented  into  clonic  contractions 
which  are  maintained  until  the  tension  upon  the  tendon  is  again  re- 
leased. Clearly,  therefore,  the  presence  of  a  true  clonus^  implies  that 
the  reflex  arcs  are  in  a  state  of  hyperirritability.  In  this  connection, 
brief  reference  should  also  be  made  to  the  fact  that  the  exaggera- 
tion of  the  spinal  reflexes  constitutes  a  cardinal  sign  in  chronic  affec- 
tions involving  the  motor  neurons  of  the  cerebrum.  In  general,  it 
may  be  said  that  a  "high"  (cerebral)  lesion  leads  to  an  exaggeration 
and  a  "low"  (spinal)  lesion  to  an  abolition  of  the  reflexes.  It  cannot 
surprise  us,  therefore,  that  an  affection  of  the  motor  areas  and  pyramidal 
tracts  is  generally  associated  with  clonic  contractions.  As  typical 
examples  of  this  condition  might  be  mentioned  hemiplegia  from  organic 
brain  disease,  or  paraplegia  due  to  myelitis.  Incomplete  transections 
of  the  cord,  as  often  result  in  fractures  of  the  spine,  produce  exagger- 
ated reflexes,  while  complete  transections  are  usually  followed  by  a 
loss  of  the  deep  reflexes. 

These  differences  may  be  explained  in  the  same  way  as  the  phe- 

^  Spurious  clonic  reflexes  are  obtained  at  times  in  hysterical  conditions.  They 
are  usually  irregular  and  poorly  sustained. 


THE    SPINAL    CORD    AS    A    CONDUCTINtJ    PATH  003 

nouienon  of  reinfort'omont  of  rcfloxcs.  Thus,  we  may  a.ssumo  that  a 
"hiji;h"  lesion  tends  to  remove  the  central  inhibition  and  to  cause  a 
"Bahnung"  of  the  reflex  circuits,  or,  that  a  "high"  lesion  gives  rise  to 
an  increase  in  the  irritability  of  central  parts  which  in  turn  induces 
a  similar  condition  in  other  divisions  of  the  nervous  system.  In 
brief,  we  may  exj)lain  this  phenomenon  either  upon  the  l)asis  of  removal 
of  cerebral  inhibition  or  upon  the  basis  of  an  overflow  of  irritability 
from  this  organ.  At  all  events,  the  facilitation  of  the  spinal  reflexes 
in  consequence  of  central  lesions,  finally  throws  the  paralyzed  muscles 
into  a  state  of  continued  contraction  or  contracture,  their  spastic 
rigidity  eventually  leading  to  contortions  of  the  extremities.  But 
a  paralysis  of  the  muscles  is  also  present  in  "low"  lesions,  because 
these  organs  then  lose  the  volitional  and  tonic  impulses  from  the  spinal 
centers.  In  the  latter  case,  however,  the  muscles  remain  in  a  perfectly 
flaccid  condition  and  finally  undergo  atrophic  changes  from  disuse. 
These  differences  in  the  intensity  of  the  reflexes  and  in  the  behavior 
of  the  muscles  are  usually  so  typical  that  they  may  be  employed  in 
ascertaining  the  exact  location  of  the  lesion. 


CHAPTER  L 


THE  SPINAL  CORD  AS  A  CONDUCTING  PATH— ITS 
TROPHIC  FUNCTION 

The  General  Structure  of  the  Spinal  Cord. — We  have  previously 
noted  that  the  spinal  cord  in  the  invertebrates  consists  of  a  series 
of  ganglia  which  severally  regulate  the  activities  of  those  segments 
of  the  body  to  which  they  have  been  apportioned.  In  further  develop- 
ment of  this  simple  reflex  system,  the  different  ganglia  have  been  con- 
nected with  one  another  and  with  the  head-ganglion  by  means  of  a 
system  of  afferent  and  efferent  fibers  which  pursue  a  course  parallel 
to  the  longitudinal  axis  of  the  body.  This  primitive  segmental 
arrangement  is  also  in  evidence  in  the  vertebrates,  with  this  modifica- 
tion, however,  that  the  reflex  functions  no  longer  exhibit  a  strictly 
local  character  but  are  now  more  closely  correlated  and  subordinated 
to  the  activities  of  the  higher  centers.  This  change  necessitates  first 
of  all  the  development  of  a  system  of  conducting  paths  which  connect 
the  different  spinal  centers  with  one  another,  and  fuse  them  into  a  har- 
monious whole.  In  the  second  place,  it  necessitates  the  formation 
of  certain  conducting  paths  which  connect  these  simple  centers  with 
those  situated  in  the  brain.  In  this  way,  two  types  of  conducting  chan- 
nels have  been  formed,  namely,  the  short  and  the  long.  The  former 
represents  the  more  primitive  reflex  system  over  which  eventually  the 


604 


THE    FUNCTION    OF    THE    SPINAL    CORD 


long  reaction  system  has  been  constructed.  For  this  reason,  it  may  be 
stated  that  reflex  action  is  a  more  primitive  function  than  the  type  of 
conduction  seen  in  the  higher  animals.  But,  while  the  spinal  cord  of 
the  latter  has  lost  much  of  its  simple  reflex  character,  it  cannot  be 
denied  that  it  still  displays  it  in  a  clearly  recognizable  manner.  Thus, 
we  have  seen  that  this  structure  contains  a  series  of  centers  for  super- 
ficial, deep  and  organic  reflexes,  and  that  the  location  of  these  centers 

roughly  corresponds  to  the  seats  of  these 
actions,  i.e.,  they  are  arranged  in  accord- 
ance with  a  definite  segmental  pattern. 
In  addition,  the  succeeding  discussion  will 
show  that  this  segmentalism  and  dissocia- 
tion of  function  has  also  entered  into  the 
construction  of  the  conducting  paths. 


Fig.  295. — The  Mexibr.\xzs  of  the 
Spixal  Cord. 
1.  Dura  mater.  2.  Arachnoid. 
.3.  Posterior  root  of  spinal  nerve. 
4.  Anterior  root  of  spinal  nerve.  5. 
Ligamentum  dentatum.  6.  Linea 
splendens.      {After  Ellis.) 


Fig.  296. — Transverse  Section' 
through  the  region  of  the  fourth 
Cervical  Vertebile. 

V,  Body  of  vertebra;  B,  verte- 
bral blood-vessels;  A',  spinal  nerve; 
RC,  ramus  communicans;  S,  spinal 
ganglion;  A,  subarachnoidal  space 
investing  spinal  cord. 


The  spinal  cord  of  man  appears  as  a  cylindrical  structure  which  extends  into 
the  vertebral  canal  for  a  distance  of  40-45  cm.,  i.e.,  to  the  level  of  the  second  or 
third  lumbar  vertebra.  Beyond  this  point  it  continues  as  a  narrow  thread,  called 
the  filum  terminale.  It  measures  12  mm.  in  diameter  and  weighs  42  grams. 
From  it  arise  thirtj'-one  pairs  of  nerves,  in  serial  order  so  that  each  pair  corre- 
sponds to  a  vertebra  and  innervates  symmetrical  areas  upon  the  two  sides  of  the 
body.  The  spinal  nerves  are  mixed  nerves,  i.e.,  they  consist  of  afferent  and  efferent 
fibers  connecting  central  parts  with  their  respective  receptors  and  effectors.  It  is 
to  be  noted,  however,  that  they  do  not  arise  as  such  directly  from  the  cord,  but 
originate  as  two  compact  bundles,  one  of  which  lies  in  close  relation  with  the  an- 
terior and  the  other  with  the  posterior  aspect  of  this  structure.  The  former 
constitute  the  anterior  (ventral)  roo.t  and  are  efferent  in  their  nature,  while 
the  latter  form  the  posterior  (dorsal)  root  and  conduct  only  in  an  afferent  direction. 
These  two  groups  of  fibers  are  joined  in  the  interv'ertebral  foramina,  their  point 
of  union  being  roughly  marked  by  a  ganglion  composed  of  the  cell-bodies  belonging 
to  the  sensory  fibers  of  the  posterior  root.     The  nerves  which  are  distributed  to 


THE    SPINAL    rORD    AS    A    COXDITCTING    PATH 


G05 


the  arms  and  lo^s  arise  from  tho  lowor  cervical  and  lower  luinbar  regions  respec- 
tively. It  is  for  this  reason  that  these  particular  se>;nients  of  the  cord  are  sorno 
u'hat  broader  than  the  others,  and  present  an  elliptical  outline,  whereas  tho  dorsal 
region  is  almost  circular. 

In  cro.s.s-section  the  spinal  conl  is  found  to  be  compo.scd  of  a  central  mass  of 
gray  matter  which  is  .surrounded  on  all  .sides  by  a  shell  of  white  matter.  The 
former  appears  on  each  side  in  the  form  of  a  crescent,  the  convex  surface  of  which 
is  turned  inward  and  is  joined  with  the  one  in  the  opposite  half  of  the  cord  Ijy  a 
transverse  band  or  commissure.  The  entire  mass  of  gray  matter  roughly  exhil)its 
the  shape  of  the  letter  H,  and  is  divided  on  each  side  into  an  anterior  or  ventral 
and  a  posterior  or  dorsal  horn,  the  intervening  substance  being  known  as  the 
intermediate  gray  matter.  The  anterior  horn  is  short  and  bulky,  while  the 
posterior  horn  is  narrow  and  slender,  extending  to  the  surface  of  the  cord  where  it 

Dorsal  niodian  septum 
Septum 
Dorsal  lateral  groove 

Dorsal  nerve  r 

Substantia  gelatinosa 

Root-fibers  entering 
gray  matter 

Processus  reticularis 
Central  canal 


Nucleus  from  which 
motor  fibers  for  mus- 
cles of  upper  limb  arise 

Ventral  white  commis- 
sure 


Ventral  nerve  root 
Ventral  median  fissure 


Fig.  297. — Cro.ss-.section  through  the  Hitman  Spinal  Cord  at  the  Level  of  the 
Fifth  Cervical  Nerve,  Stained  by  the  Method  of  Weigert-Pal,  which  Color.s  the 
White  Matter  Dark  and  Leaves  the  Gray  Matter  Uncolored.  {From  Cunning- 
ham's Anatomy.) 


is  invested  by  the  substantia  gelatinosa.  The  latter  is  known  as  the  caput  cornu 
posterioris.  In  the  lower  cervical  and  thoracic  regions,  the  intermediate  gray 
matter  becomes  unusually  prominent  and  forms  here  the  so-called  lateral  horn. 
The  center  of  the  commissure  uniting  the  right  and  left  halves  of  the  gray  matter, 
is  occupied  by  a  canal  (0.5-1.0  mm.  in  diameter)  which  extends  throughout  the 
entire  length  of  the  cord,  and  eventually  communicates  with  the  lymphatic  spaces 
of  the  brain.  This  is  the  remains  of  the  primitive  neural  canal  of  the  embryo. 
It  is  surrounded  by  substantia  gelatinosa  and  its  walls  are  lined  with  cylindrical 
epithelium.  It  is  filled  with  liquor  spinalis,  a  lymphatic  fluid  of  the  same  char- 
acter as  the  liquor  contained  in  the  cerebral  spaces. 

The  white  matter  of  the  spinal  cord  is  made  up  of  different  bundles  of  sensory 
and  motor  fibers  which  are  arranged  in  such  a  way  that  they  fill  in  the  different 
spaces  externally  to  the  gray  matter.  They  are  medullated,  but  possess  no 
neurolemma  and  run  within  tubes  formed  by  the  supporting  neuroglia  tis.sue.  In- 
asmuch as  the  entire  mass  of  the  spinal  cord  is  divided  into  two  halves  by  the  ante- 
rior and  posterior  median  fissures,  the  white  matter  of  each  side  presents  itself  in 


60G  THE    FUNCTION    OF    THE    SPINAL    CORD 

three  columns  or  funiculi,  namely:  (a)  one  situated  between  the  anterior  furrow 
and  the  anterior  horn  of  the  gray  matter,  (h)  one  neighboring  upon  the  lateral 
surface  of  the  gray  matter  and  (c)  one  located  between  the  posterior  fissure  and 
the  posterior  horn  of  the  gray  matter.  We  shall  see  later  on  that  the  anterior, 
lateral  and  posterior  funiculi  are  in  turn  made  up  of  several  tracts  or  fasciculi 
which  are  anatomically  and  functionally  distinct  from  one  another.  It  is  also  to 
be  noticed  that  the  median  fissures  do  not  extend  directly  to  the  commissure  of 
the  gray  matter,  but  permit  bridges  of  white  matter  to  intervene.  These  are  the 
so-called  anterior  and  posterior  commissures.  The  fissures  themselves  contain 
a  process  of  the  pia  mater  which  invests  the  external  surface  of  the  cord,  and, 
together  with  the  arachnoid  and  dura  mater,  forms  a  protective  envelope  for  this 
structure. 

The  Functional  Basis  of  the  Gray  Matter.— The  gray  matter 
consists  of  the  supporting  neuroglia  in  which  are  imbedded  numerous 
ceh-bodies  and  the  beginning  portions  of  their  processes.  The  former 
appears  as  a  felt-hke  network  of  fibers  with  scattered  nuclei.  Around 
the  central  canal  and  in  the  vicinity  of  the  entrajice  of  the  posterior 

root,  these  reticular  spider-shaped 
cells  are  especially  small  and  nu- 
merous, forming  here  the  so-called 
substantia  gelatinosa  of  Rolando. 
The  nerve  cells  of  the  spinal  cord 
are  very  numerous  and  exhibit  a 
variety  of  shapes  and  sizes.  It 
should  also  be  noted  that  they  oc- 
cupy definite  areas  of  the  gray 
matter  and  extend  as  distinct  colo- 
FiG.  298.-A  Neuroglia-cell,  Isolated  nies  for  some  distance  up  and  down 
IN  33  Per  Cent.  Alcohol.    (Quain.)     in  the  cord.     In  the  anterior  hom, 

where  they  are  especially  promi- 
nent, they  are  arranged  in  three  groups.  The  median  group  is  situ- 
ated near  the  middle  line  and  its  axons  may  be  traced  across  to  the 
other  side  through  the  anterior  commissure  of  the  white  matter.  The 
anterior  group  consists  of  large  multipolar  cells,  the  axons  of  which 
pass  outward  in  the  anterior  roots  of  the  cord  and  are  distributed 
eventually  to  the  different  effectors  of  the  spinal  system.  Some  of 
these  cells,  as  we  shah  see  later,  send  their  axons  into  neighboring 
sympathetic  gangha  and  thus  form  the  efferent  bridges  between  the 
cerebrospinal  and  sympathetic  systems.  The  aforesaid  cells  are  es- 
pecially numerous  in  the  cervical  and  lumbar  segments  of  the  cord 
which,  as  we  have  seen  above,  innervate  the  anterior  and  posterior 
extremities.  The  posterior  group  of  cells  is  present  in  those  regions 
of  the  cord  in  which  the  lateral  horn  is  well  developed.  A  very  promi- 
nent column  of  cells  also  extends  through  the  dorsal  and  inner  area 
of  the  cord  near  the  base  of  the  posterior  root.  These  cells  l)egin  at 
the  level  of  the  seventh  or  eighth  cervical  nerve  and  reach  downward 
as  far  as  the  second  or  third  lumbar  nerve.  They  are  most  conspicuous 
in  the  thoracic  region,  their  large  bodies  being  elongated  in  the  longi- 


THE    SPINAL    LORD    AS    A    ('(J\DUCTIN(i    PATH  (>(j7 

tudinal  axis  of  tlie  cord.  Their  axons  tend  ol)li(jU('ly  outward  into 
tho  so-called  direct  cerel)ellar  tract  of  the  lateral  white  matter.  Some 
of  these  processes  also  pass  into  the  fasciculi  next  to  the  posterior 
median  fissure.  Posterior  to  this  group  of  cells,  constituting  the 
so-called  Clarke's  vesicular  column,  we  find  a  few  cells  distrii)uted 
in  an  irregular  manner  through  the  posterior  horn.  The  cells  of  the 
sensory  fil)ers  forming  the  posterior  roots,  are,  of  course,  situated 
outside  the  cord,  in  the  spinal  ganglia. 

When  considered  from  the  standpoint  of  gross  and  minute  anatomy, 
the  white  matter  of  the  spinal  cord  presents  itself  as  three  funiculi 
which  in  turn  are  divided  into  several  fasciculi.  The  physiologist, 
however,  is  more  directly  concerned  with  the  function  of  these  col- 
lections of  nerve  fibers  and  hence,  his  unit  is  the  tract,  i.e.,  bundles 
of  fibers  possessing  an  identical  action.  But  as  several  of  these 
tracts  have  clearly  defined  anatomical  boundaries,  these  terms  are 
frequently  used  interchangingly.  As  far  as  the  cells  of  the  gray 
matter  are  concerned,  is  is  important  to  determine  the  tracts  to  which 


Fig.  299. — Spinal  Ganglion  of  an  Embryo  Duck;  Composed  of  Dlaxonic  Ner\t;-cells. 

{van  Gehuchten.) 

these  cells  are  functionally  related.  Upon  this  basis  we  may  divide 
them  into  two  main  groups,  namely,  local  and  general.  As  the  former 
are  intended  to  establish  a  close  relationship  between  the  cells  situated 
in  different  parts  of  the  gray  matter  and  at  different  levels  of  the  cord, 
they  are  associative  (tautomeric)  or  commissural  (heteromeric)  in 
their  nature.  In  this  class  should  be  placed  the  cells  of  Clarke's 
column,  because  they  are  tributary  elements  to  the  direct  cerebellar 
and  posterior  tracts.  The  same  is  true  of  the  cells  of  the  median 
group,  because  they  send  their  axons  across  the  middle  line  to  the 
opposite  gray  matter  and  thus  become  commissural  in  their  nature. 
Another  type  of  associative  cell  is  the  cell  of  Golgi  which  is  found 
chiefly  in  the  posterior  horn.  Its  axon  does  not  pass  far  away  from 
the  cell-bod}^,  but  ramifies  extensively  to  estabhsh  connections  with 
neighboring  cells  at  any  level  of  the  cord. 

The  group  of  the  general  cells  is  made  up  of  those  cells  which  are 
concerned  with  bringing  the  cord  into  relation  with  the  higher  centers 
as  well  as  with  the  peripheral  end-organs.  Chief  among  these 
are   the    large    ganglion    cells    in    the    anterior   horn,   measuring  57 


608  THE    FUNCTIOX    OF    THE    SPINAL    CORD 

to  135^.  They  are  efferent  in  their  nature  and  innervate  the  skeletal 
musculature.  Second  in  importance  are  the  somewhat  smaller  cells 
of  the  lateral  horn,  the  axons  of  which  leave  the  cord  by  way  of  the 
anterior  roots  but  finally  separate  to  enter  the  sympathetic  ganglia. 
In  this  way,  the  white  ramus  communicans  is  formed,  constituting 
one  of  the  efferent  bridges  between  the  cerebrospinal  and  sympathetic 
systems.  As  has  been  stated  above,  the  afferent  cells  of  the  cord  are 
contained  in  the  spinal  ganglia  which  are  situated  upon  the  different 
posterior  roots.  Other  afferent  cells  of  the  projection  system  form  the 
nucleus  gracihs  and  cuneatus,  the  end-stations  of  the  posterior  fasciculi. 


Fig.  300. — Spixal  Gangliox-cells  showen'g  Transition'  from  Bipolar    to    Unipolar 

Condition.      (Holmgren.) 

The  Functional  Basis  of  the  White  Matter — The  characteristic 
appearance  of  the  gray  matter  and  white  matter  is  dependent  upon 
certain  structural  differences.  The  former  is  composed  principally 
of  cell-bodies  and  the  dendrites  and  axons  in  their  immediate  vicinity, 
while  the  latter  consists  cliiefly  of  axons  enveloped  in  their  medullary 
sheaths,  in  other  words,  of  nei-^'e  fibers.  It  is  evident  that  the  white 
matter  decreases  constant!}'  in  the  direction  toward  the  tip  of  the  cord, 
because  the  number  of  fibers  still  retained  at  its  lumbar  level  is  much 
smaller  than  that  near  the  medulla.  Fibers  leave  this  structure  all 
the  time  to  reach  peripheral  parts,  and  fibers  enter  it  continuously  to 
attain  the  higher  centers.  This  does  not  imph',  however,  that  there 
is  an  absolute  proportion  between  these  fibers  and  the  total  area  of  the 
white  matter  at  different  levels  of  the  cord,  because  a  large  number  of 
them  do  not  pass  all  the  way  through,  but  form  merely  local  reflex 
connections.  In  addition,  it  should  be  noted  that  the  relative  amounts 
of  gray  and  white  matter  vary  at  different  levels  of  the  cord,  thereby 
enabhng  us  to  determine  with  accm-ac}'  from  what  particular  area  any 
given  section  has  been  taken.  Sections  from  its  lumbar  region  are 
characterized  by  a  copious  amount  of  graj-  matter,  while  those  from 
its  cei-\'ical  portion  are  relatively  poor  in  this  substance.  Besides,  as 
especially  large  numbers  of  fibers  arise  in  its  cervical  and  lumbar  seg- 
ments at  the  points  of  origin  of  the  plexuses  of  the  arms  and  legs,  the 
total  cross-area  of  the  cord  must  be  markedh'  increased  at  these  levels. 

The  posterior  roots  serve  as  points  of  entrance  for  about  haK  a 
miUion  fibers  and  we  may  assume  that  an  equal  number  leaves  by 
way  of  the  anterior  roots.     The  afferent  impulses  which  are  in  this 


THE    SPINAL    COUD    AS    A    CONDUCTING    PATH 


609 


way  poured  into  the  central  nervous  system  are  of  different  kinds  and 
may  either  remain  within  the  domain  of  the  cord  or  may  be  conveyed 
onward  to  liigher  centers.  The  same  holds  true  of  the  efferent  im- 
pulses. While  some  of  them  arise  in  the  ])rain  and  neighboring  parts, 
some  also  originate  in  the  motor  cells  of 
the  cord  itself  Obviously,  therefore,  th(i 
conduction  system  of  the  cord  is  arranged 
in  the  form  of  a  long  or  projection  system 
and  a  short  or  reflex  system.  The  latter 
is  the  more  primitive,  and  hence,  we  find 
that  it  occupies  a  position  next  to  the 
gray  matter,  while  the  projection  paths 
correlating  peripheral  parts  with  the 
brain,  form  the  external  shell  of  the 
spinal  white  matter. 

The  axons  of  the  nerve  cells  uniting 
these  widely  separated  portions  of  the 
nervous  system,  are  of  different  lengths. 
It  is  said  that  the  motor  neurons  in 
the  anterior  horn  of  the  spinal  gray 
matter  reach  all  the  way  to  the  peripherj^ 
and  attain  a  length  of  1.0  m.  The  same 
holds  true  of  the  motor  cells  of  the  cere- 
bral cortex,  the  axons  of  which  terminate 
low  down  in  the  cord.  In  many  cases, 
however,  two  or  three  neurons  are  re- 
quired to  cover  a  distance  of  only  a  few 
centimeters.  In  adult  life,  the  axons  of 
the  spinal  white  matter  are  surrounded 
by  medullary  sheaths  but  not  by  neuro- 
lemma. They  differ,  therefore,  in  this 
regard  from  ordinary  nerve  fibers.  They 
are  of  different  size  and  give  off  small 
collaterals  which  connect  with  the  gray 
matter  at  different  levels  of  the  cord. 
Externally,  they  are  invested  by  a  tube 
formed  l^y  neuroglia  tissue. 

The  Methods  Used  for  the  Localiza- 
tion of  Spinal  Conduction. — We  have 
previously  seen  that  the  white  matter  of 
the  cord  is  arranged  as  anatomically  dis- 
tinct bundles.  The  question  may  now 
be  asked  whether  these  morphological 
units  also  represent  physiological  entities.  In  other  words,  can  it  be 
proven  that  the  different  fasciculi  possess  a  different  origin  and  desti- 
nation so  that  their  direction  of  conduction  assumes  a  specific  char- 
acter?    AVhile  the  investigations  pertaining  to  this  topic  cannot  be 

39 


Fig.  301. — Sections  through 
Different  Regions  of  the  Spinal 
Cord. 

A,  At  the  level  of  the  sixth  cer- 
vical nerve;  B,  at  the  mid-dorsal 
legion;  C,  at  the  center  of  the 
lumbar  enlargement;  D,  at  the  up- 
per part  of  the  conus  meduUaris. 
1.  Posterior  roots.  2.  Anterior 
roots.  3.  Posterior  fissure.  4. 
Anterior  fissure.  5.  Central  canal. 
(After  Schwalbe.) 


GIO 


THE    FUNCTION    OF    THE    SPINAL    CORD 


regarded  as  at  all  complete,  the  material  already  at  hand  suffices  to 
show  that  the  spinal  cord  contains  definite  tracts  which  in  the  main 
correspond  with  the  anatomical  grouping  previously  discussed.  The 
methods  employed  to  trace  the  course  of  these  different  neuron  sys- 
tems are  as  follows:^ 

(a)  Morpfiological. — Different  procedures  of  staining  have  been  made  use  of 
in  order  to  differentiate  the  cell-bodies  and  their  processes  more  clearly  from  the 
surrounding  tissue.  The  impregnation  procedures  of  Weigert  and  Golgi  consist 
in  hardening  the  preparation  in  chromate  or  bichromate  and  subjecting  it  subse- 
quently to  a  solution  of  silver  nitrate  or  mercuric  chlorid.  The  silver  or  mercuric 
chromate  precipitates  are  not  diffuse,  but  are  restricted  to  certain  parts  of  the 
neuron  and  may  be  bleached  sufficiently  to  allow  the  tracing  of  the  processes  in 


Fig.  302.^Schema  of  the  Tracts  tx  the  Spinal  Cord.     (Kolliker.) 
g,  Fasciculus  gracilis;  b,  fasciculus  cuneatus;  pc,  fasciculus  cerebrospinalis  lateralis; 
pd,    fasciculus    cerebrospinalis    anterior;  /,    fasciculus    cerebellospinalis;    gr,    fasciculus 
anterolateralis  superficialis. 

rather  thick  sections.     Ehrlich  has  advocated  the  intravatam  staining  with  methy- 
lene-blue. 

The  method  of  differential  stainmg  is  frequently  employed  as  a  means  of 
recognizing  medullated  and  non-medullated  nerve  fibers.  It  has  been  pointed  out 
by  Flechsig  that  the  newly-formed  axons  are  non-medullated,  but  acquire  a  sheath 
when  developed  sufficiently  to  become  functional.  Now,  as  the  different  parts  of 
the  nervous  system  attain  their  full  development  in  a  definite  sequence,  it  cannot 
surprise  us  to  find  that  the  myelination  of  the  various  fiber  groups  takes  place 
successively  and  at  certain  intervals  from  one  another.  Moreover,  as  the  projec- 
tion system  is  the  most  recent  acquisition  of  the  nervous  system,  we  are  justified  in 
assuming  that  the  pyramidal  tracts,  connecting  the  cerebrum  with  the  cord,  re- 

^  Galenus  compared  the  spinal  cord  to  a  stream  which  distributes  nervous  energy 
to  all  parts  of  the  body.  Oribasius  describes  the  effects  following  sections  of  the 
cord.     These  are  also  discussed  in  the  writings  of  Hippocrates. 


THE    SPINAL   CORD    AS    A    CONDUCTING    PATH  Oil 

ceive  their  luodulhiry  coverings  last  of  all.  In  this  assumption  we  are  correct, 
because  the  niyelination  of  these  fibers  is  not  conipletcfl  until  the  first  month  after 
birth.  Next  in  order  follow  those  fibers  which  connect  the  cerebellum  with  the 
spinal  cord.  These  also  belong  to  the  long  system.  Following  the  same  course 
of  reasoning,  it  may  be  assumed  that  the  fibers  composing  the  more  primitive 
system,  which  regulates  the  reflex  life  of  the  aninuil,  acquire  their  medullary  sheaths 
long  l)efore  the  others.  In  this  assumption  we  are  al.so  correct,  because  the  fibers 
connecting  the  centers  in  the  spinal  cord  with  the  sensory  and  motor  organs  at  the 
periphery,  are  myelinated  first.  From  here  the  niyelination  progresses  to  those 
intraspinal  fibers  which  connect  the  different  segments  of  the  cord.  In  the  human 
embryo,  this  process  is  practically  completed  at  the  time  of  birth. 

The  third  morphological  method  consists  in  tracing  the  course  of  degenerating 
nerve  fibers.^  It  has  been  pointed  out  above,  that  a  nerve  fiber,  when  separated 
from  its  cell-body,  is  eventually  converted  into  a  band-fiber.  This  process  neces- 
sitates the  conversion  of  the  phosphorized  fat  of  the  myelin  into  fat  which  is 
absorbed  and  displaced  by  fibrous  tissue.  In  studying  the  distribution  of  the 
spinal  fibers,  it  is  possible  to  divide  the  cord  in  places  and  to  trace  the  degenerating 
fibers  by  the  method  of  staining.  The  sections  are  hardened  in  a  bichromate 
solution  and  are  then  placed  in  a  mixture  of  osmic  acid  and  bichromate.  Normal 
myelin  remains  unstained,  while  its  fatty  derivative  assumes  a  black  color.  Ob- 
viously, the  degeneration  of  a  tract  above  the  section  implies  that  the  trophic 
centers  (cell-bodies)  of  these  fibers  are  situated  below  the  lesion  and  that  the  de- 
generation is  ascending  in  its  character.  Quite  similarly,  a  degeneration  below  the 
cut  signifies  that  the  cell-bodies  are  located  above  the  lesion  and  that  the  degenera- 
tion is  descending  in  its  nature.  This  method  has  been  employed  by  Waller  in 
his  determination  of  the  function  of  the  roots  of  the  cord. 

It  should  also  be  remembered  that  the  localization  of  the  cell-bodies  of  a  given 
tract  of  fibers  does  not  always  necessitate  a  repeated  transection  of  the  cord  at 
different  levels,  but  may  also  be  effected  by  means  of  staining  the  suspected  cells. 
It  has  been  pointed  out  above  that  the  degeneration  following  upon  the  separation 
of  a  nerve  fiber  from  its  cell-body,  does  not  remain  confined  to  the  peripheral  stump 
of  the  cut  fiber,  but  also  involves  its  central  end  and  corresponding  cell-body. 
This  central  degeneration  which  is  known  as  retrogressive  degeneration,  finds  its 
cause  in  a  trophic  disturbance  of  the  cell-bodj^  in  consequence  of  the  inacti\'ity 
forced  upon  it  by  its  separation  from  its  end-organs  and  neighboring  neurons. 
In  their  final  atrophic  state,  these  cells  may  readily  be  recognized  after  staining 
with  methylene  blue  or  toluidin  blue.  They  exhibit  a  swollen  and  eccentric  nu- 
cleus as  well  as  indistinct  and  diffusely  stained  chromophil  granules. 

{h)  Physiological. — The  early  view  of  ^'anDeen  and  Schiff,  that  the  white 
matter  of  the  spinal  cord  is  non-receptive  to  electrical  stimuli,  has  been  thoroughly 
disproved  by  the  work  of  Fick,  Biedermann,  and  others.  It  must  be  admitted, 
however,  that  the  results  of  the  direct  stimulation  of  the  different  tracts  of  the 
cord  leave  much  to  be  desired,  because  the  paths  are  not  sufficiently  separated 
from  one  another  to  be  able  to  obtain  sharply  differentiated  effects.  In  spite  of 
this  difficulty  this  method  has  proved  distinctly  helpful  as  an  adjunct  to  other 
procedures.  By  applying  a  galvanometer  or  capillary  electrometer  to  the  different 
spinal  paths,  Eckhard,  Gotch  and  Horsley^  have  succeeded  in  tracing  the  action 
current  which  is  produced  whenever  the  motor  areas  of  the  cerebrum  are  stimu- 
lated. This  method  has  been  amplified  by  the  procedure  of  fractional  di\asion 
of  the  spinal  cord.  Obviously,  the  di\'ision  of  certain  spinal  tracts  enables  us  to 
determine  whether  these  electrical  variations  continue  even  after  the  establishment 
of  this  block  between  the  motor  area  and  the  level  of  the  galvanometer.  This 
procedure  is  also  appUcable  to  the  tracing  of  the  circuits  of  the  common  spinal 
reflexes. 

1  Employed  by  Tiirck  in  1S51  upon  sections  of  the  diseased  spinal  cord  of  man. 
-  Proc.  Royal  Society,  London,  1888. 


612 


THE    FUNCTION    OF    THE    SPINAL    CORD 


(c)  Clinical  Observations. — A  study  of  the 
clinical  pictures  of  diseases  of  the  spinal  cord 
must  prove  of  especial  value  if  the  symptoms 
are  subsequently  compared  with  the  record  of 
the  autopsy.  Naturally,  the  difficulties  con- 
nected with  an  accurate  localization  of  motor  and 
sensory  defects  are  minimized  in  man,  owing  to 
his  ability  to  observe  and  to  describe  his  own 
symptoms. 

Classification  of  the  Fasciculi  of  the 
Spinal  Cord. — The  white  matter  of  the 
spinal  cord  is  divided  into  three  fascicuH, 
an  anterior,  a  lateral  and  a  posterior.^ 
The  first  two  are  often  called  the  antero- 
lateral fasciculi,  because  the  rather  scat- 
tered distribution  of  the  axons  forming 
the  anterior  root,  causes  the  boundary 
line  between  these  two  columns  to  become 
somewhat  indefinite.  Furthermore,  as 
the  cervical  and  upper  thoracic  segments 
of  the  cord  show  slight  furrow-like  depres- 
sions at  the  points  of  exit  of  the  fibers  of 
the  anterior  roots,  the  anterior  funiculus 
seems  to  be  composed  of  two  fascicuU, 
namely,  the  anteromedian  and  the  antero- 
lateral. A  similar  condition  exists  pos- 
teriorly, this  funiculus  appearing  as  the 
posteromedian  and  posterolateral  fasciculi. 
The  following  subdivisions  may  easily  be 
made  out: 

1.  The  anterior  funiculus  comprises  the  area 
between  the  anterior  median  fissure,  and  the  an- 
terior root.  It  is  motor  in  its  function  and  is 
divided  into  the : 

(a)  Fascicuhis  cerehrospinalis  anterior,  also 
known  as  Tiirck's  column,  or  the  direct  (anterior) 

pyramidal  tract. 


-MERCURY 


'SULPHURIC  ACID  10% 


<( 


MICROSCOPE 


twk 


-MERCURY 


Fig.  30.3. — Schema  iLLrsTRATiNG  the  Experiment  foe  De- 
termining THE  Number  of  Separate  Nerve  Impulses  Passing 
Down  the  Spinal  Cord  upon  Stimulation  of  the  Cortex. 
(Horsley.) 

E,  E,  electrodes,  intended  to  be  on  the  "leg  area."  Where 
the  cord  is  interrupted,  one  non-polarizable  electrode  is  placed 
over  the  cut  end  of  the  pyramidal  fibers  going  to  the  lumbar  en- 
largement; the  other,  on  the  side  of  the  cord.  These  lead  to  the 
capillary  electrometer,  in  which  the  column  of  mercury  moves 
each  time  an  impulse  passes. 


It  lies  next  to  the 
median  fissure  and 
extends  downward 
as  far  as  the  mid- 
thoracic  region. 
Its  caliber  de- 
creases constantl}', 
because  the  fibers 
composing  it  enter 

1  Von  Bechterew, 
Die  Funktionen  der 
Nervencentra, 
Jena,  1908-1911, 
and  Edinger,  Yergl. 
Anat.  des  Gehirns, 
Leipzig,  1911. 


THE    SPINAL    CORD    AS    A    CONDUCTING    PATH  613 

the  gray  matter  of  the  opposite  side  by  way  of  the  anterior  white  commissure. 
We  shall  see  later  on  that  these  fibers  arise  in  the  motor  cortex  of  the  cerebrum 
(cells  of  Betz)  of  the  same  and  opposite  side,  and  are  therefore  descending  in  their 
character. 

(fc)  Fasciculnti  anterior  /rroimus,  also  called  the  anterior  ground  bundle  or 
root  zone.  This  column  occupies  the  area  next  to  the  anterior  root  and  extends 
throughout  the  cord.  The  fibers  composing  it  are  commissural  in  their  character, 
i.e.,  they  bring  different  segments  of  the  gray  matter  into  functional  relation. 
This  end  they  accomplish  by  passing  to  higher  as  well  as  to  lower  levels  of  the  cord, 
where  they  reenter  the  gray  matter  uiid  nuike  connections  with  other  cells. 

2.  The  lateral  funiculu.s  embraces  the  white  matter  l)etween  the  anterior  and 
posterior  roots  and  is  composed  of  the: 

(a)  Fasciculus  cerebrospinalis  lateralis,  also  called  the  lateral  or  crossed  pyram- 
idal tract.  It  occupies  the  posterior  area  of  this  funiculus,  but  its  position  varies 
somewhat  at  different  levels  of  the  cord.  In  the  lumbar  region,  it  comes  right  to 
the  surface,  while  in  the  cervical  and  thoracic  regions  it  remains  at  some  distance 
from  it.  It  is  covered  here  by  a  layer  of  fibers  composing  the  fasciculus  cere- 
bellospinalis.  Its  fibers  arise  in  the  motor  area  of  the  cerebrum  (cells  of  Betz), 
but  cross  to  the  opposite  side  of  the  body  in  the  medulla.  In  their  downward 
course  through  the  cord  they  terminate  successively  at  different  levels  of  the  gray 
matter  so  that  the  size  of  the  entire  column  diminishes  gradually  from  above 
downward. 

(6)  Fasciculus  spinocerebellaris,  also  designated  as  the  direct  cerebellar  or 
Flechsig's  column.  It  lies  externally  to  the  crossed  pyramidal  tract.  Its  fibers 
take  their  origin  in  the  cells  of  Clark's  column.  From  here  they  pass  obUquely 
outward  and  upward  and  finally  terminate  in  the  cerebellum,  where  they  decussate 
in  part  in  the  superior  vermiform  lobe  of  this  structure. 

(c)  Fasciculus  anterolateralis  superficialis,  also  known  as  Gower's  tract.  It 
occupies  the  external  realm  of  the  lateral  funiculus  in  front  of  the  crossed  pyra- 
midal tract  and  extends  forward  as  far  as  the  anterior  roots.  It  begins  in  the 
lumbar  segment  and  forms  a  compact  strand  through  the  entire  cord.  The  largest 
number  of  its  fibers  arise  in  the  opposite  gray  matter  and  cross  the  midline  by  way 
of  the  w-hite  commissure.  The  uncrossed  fibers  find  their  origin  in  relation  with 
axons  which  have  passed  through  the  graj'  commissure  and  have  come  from  cell- 
bodies  in  the  gray  matter  of  the  opposite  side.  In  the  brain-stem  this  column 
divides  into  several  groups  of  fibers  which  terminate  in  the  reticular  nuclei,  the 
cortex  of  the  cerebellum,  the  tectum,  the  substantia  nigra  and  the  thalamus. 

(d)  Fasciculus  lateralis  proprius  or  lateral  ground  bundle.  This  tract  forms  a 
narrow  layer  next  to  the  external  surface  of  the  gray  matter.  It  is  believed  to  be 
composed  of  efferent  and  afferent  fibers,  the  former  being  situated  in  front.  Its 
function  seems  to  be  associative,  because  its  fibers  originate  in  cells  of  the  spinal 
gray  matter  and  terminate  at  levels  above  and  below  their  points  of  origin. 

3.  The  posterior  funiculus  comprises  the  white  matter  between  the  posterior 
median  fissure  and  the  posterior  roots.      It  consists  of  the : 

(a)  Fasciculus  gracilis,  also  called  the  column  of  Goll  or  the  posteromedian 
tract.  It  is  situated  next  to  the  posterior  fissure  and  begins  with  the  posterior 
root  of  the  coccygeal  nerve.  Beginning  at  this  level,  it  gradually  increases  in  size 
owing  to  the  acquisition  of  the  root  fibers  of  higher  nerves  of  the  same  side.  Above 
the  fifth  thoracic  nerve  it  retains  its  caliber  or  becomes  even  somewhat  smaller, 
because  while  it  ceases  here  to  receive  root  fibers,  it  continues  to  give  off  collaterals 
to  the  successive  segments  of  the  gray  matter.  It  terminates  in  the  nucleus  funi- 
culi gracilis  of  the  medulla. 

(b)  ^Fasciculus  cuneatus,  also  known  as  the  column  of  Burdach  or  posterolateral 
tract.  It  lies  next  to  the  posterior  horn  and  begins  in  the  middle  thoracic  region. 
As  it  acquires  new  fibers  constantly,  its  size  increases  from  below  upward  until  it 
terminates  in  the  nucleus  funiculi  cuneati  of  the  medulla.  Its  fibers  are  derived 
from  the  successive  posterior  roots  of  the  spinal  nerves  of  the  same  side  as  well  as 


614 


THE    FUNCTION    OF    THE    SPINAL    CORD 


from  cells  of  the  corresponding  gray  matter.     The  latter  are  short  fibers,  i.e., 
associative  in  their  function,  while  the  former  belong  to  the  projection  system. 

Classification  of  the  Tracts  of  the  Spinal  Cord. — In  accordance 
with  the  foregoing  histological  discussion,  it  will  be  seen  that   the 


Fig.  304. — Diagram  Showing  the  Course,  Origin  and  Termination  of  the  Fibers  of 
THE  Principal  Tracts  of  the  White  Matter  of  the  Spinal  Cord. 
Descending  tracts:  la,  a  fiber  of  the  crossed  pyramid  or  corticospinal  tract;  lb,  an 
uncrossed  fiber  of  the  pyramid  or  corticospinal  tract  passing  to  the  lateral  column  of 
the  same  side;  2,  a  fiber  of  the  ventral  pyramid  or  cortico-spinal  tract;  3,  a  fiber  of  the 
ventrolateral  descending  or  pontospinal  tract;  4,  a  fiber  of  the  rubrospinal  tract;  5, 
a  fiber  of  the  common  tract.  Ascending  tracts:  6,  a  fiber  of  the  dorsomesial  spino- 
bulbar  tract;  7,  fibers  of  the  dorsolateral  spinobulbar  tract;  9,  one  belonging  to  the 
dorsal  spinocerebellar;  10,  a  fiber  of  the  ventral  spinocerebellar  tract.  (Quain,  Ele- 
vients  of  Anatomy.) 

different  fasciculi  of  the  spinal  cord  constitute  different  descending 
and  ascending  tracts.  In  this  connection  brief  reference  should  also 
be  made  to  a  number  of  small  and  narrow  tracts  which  have  been 


THE    SPINAL    CORD    AS    A    CONDUCTING    PATH 


015 


localized  in  those  fasciculi  at  different  levels  of  the  cord.  But,  the 
origin  and  distribution  of  the  latter  are  still  rather  obscure  so  that  the 
following  iihysioiogical  classification  must  necessarily  be  subject  to 
frequent  revision. 

1.  Descending  Trnrts.  (o)  Pyramidal  tracts. — We  have  previously  seen  that 
tlie  fibers  coniposiiifi  the  direct  (anterior)  and  crossed  (lateral)  pyramidal  tracts, 
ori}i;inate  in  tiie  lar;!;e  cells  uf  Betz  of  the  motor 
areas  of  the  cerel)rum.  Hence,  an  injury  to 
these  regions  or  a  transverse  division  of  these 
paths  at  a  lower  level  must  result  in  a  down- 
ward degeneration  of  these  tracts.  It  should  / 
he  rememliered,  however,  that  by  far  the  largest/', 
number  of  those  fibers  cross  to  the  opposite  side^-' 
so  that,  say,  the  left  cerel)ral  hemisphere  eventu- 
ally obtains  control  over  the  musculature  of  the 
right  side  of  the  body,  and  vice  versa.  Only  a 
few  fibers  remain  on  the  same  side,  where  they 
eventually  enter  the  lateral  column.  The  afore- 
said crossing  is  effected  principally  in  the  pyra- 
midal decussation  in  the  lower  region  of  the 
medulla,  but  in  part  also  in  the  spinal  cord  itself. 
Thus,  it  appears  that  the  crossed  pyramidal 
tract  is  made  up  of  fibers  which  have  gained 
the  opposite  side  in  the  medulla,  w'hile  the  an- 
terior pyramidal  tract  comprises  in  addition  a 
certain  number  of  fibers  which  have  failed  to 
cross  in  the  medulla  but  which  seek  the  opposite 
side  gradually  by  way  of  the  anterior  commis- 
sure. As  this  crossing  is  completed  in  the  mid- 
dorsal  region,  these  anterior  tracts  disappear 
at  this  level.  In  fact,  it  is  said  that  they  are 
entirely  wanting  in  about  15  per  cent,  of  human 
spinal  cords,  because  in  these  cases  the  decussa- 
tion is  had  solely  in  the  medulla,  the  fibers  being 
distributed  from  here  exclusively  to  the  crossed 
pyramidal  tract.  ^  This  condition  also  prevails 
in  the  cat,  while  in  the  mole  the  fibers  remain 
uncrossed  and  descend  anteriorly.  In  the  frog 
this  system  is  absent. 

It  may  be  concluded,  therefore,  that  the 
pyramidal  tracts  are  efferent  in  their  nature  and 
form  the  motor  path  for  those  impulses  which 
originate  in  the  motor  cells  of  the  cerebrum  and 
are  finally  transferred  to  the  large  motor  neurons 
in  the  anterior  horn  of  the  spinal  gray  matter, 
whence  the.v  are  distributed  to  the  skeletal  mus- 
culature. From  this  discussion  it  maj^  be  in- 
ferred that  they  are  the  chief  constituents  of 
the  efferent  side  of  the  cerebral  projection  sys- 
tem. Hence,  any  injury  to  this  path  must  re- 
sult in  a  loss  of  voluntary  control  over  the  action  of  the  corresponding  skeletal 
muscles,  but  naturally,  the  ordinary  reflex  movements  of  the  cord  are  not  inter- 
fered with  unless  the  lesion  is  situated  at  a  low  level.  High  lesions  of  the  pyra- 
midal system,  as  has  been  stated  above,  really  tend  to  exaggerate  the  activity' 

1  Simpson,  Quart.  Jour,  of  Ex-p.  Physiol.,  viii,  1914,  79;  also:  Lenhossek,  Bau 
des  Nervensystemes,  1895. 


Fig.  305. — Schema  Represent- 
ing THE  Course  of  the  Fibers  of 
THE  Pyramidal  System. 

1,  Fibers  to  the  nuclei  of  the 
cranial  nerve;  2,  uncrossed  fibers 
to  the  lateral  pyramidal  fasciculus; 
3,  fibers  to  the  anterior  pyra- 
midal fasciculus  crossing  in  the 
cord ;  4  and  5,  fibers  that  cross  in 
the  pyramidal  decussation  to 
make  the  lateral  pyramidal  tract 
of  the  opposite  side.      (Howell.) 


616  THE    FUNCTION    OF    THE    SPINAL    CORD 

of  the  spinal  cord.  It  is  to  be  noted,  however,  that  these  defects  differ  in  different 
animals  in  accordance  with  the  state  of  development  of  these  tracts.  They  are 
most  apparent  in  the  apes  and  man  and  less  evident  in  lower  animals,  in  which 
the  pyramidal  system  is  always  rather  incomplete.  In  the  latter,  other  motor 
paths  serve  to  bring  the  spinal  nuclei  into  unison  with  the  higher  centers.  This 
is  also  true  of  the  dog,  because  the  division  of  the  pyramids  causes  merely  a  par- 
tial paralysis  of  the  muscles,  and  still  permits  the  stimulation  of  the  cerebral 
cortex  to  evoke  certain  movements.'  Clearly,  therefore,  the  results  obtained  by 
experiments  upon  lower  animals  cannot  be  directly  applied  to  man. 

(h)  The  anterior  tectosjrinal  bundle,  or  Held's  bundle,  lies  just  beside  the  entrance 
to  the  anterior  median  fissure.  It  has  its  origin  in  the  superior  quadrigeminal 
colliculus  and  descends  through  the  dorsal  tegmented  decussation,  midbrain,  pons 
and  upper  half  of  the  medulla  to  a  place  between  the  pj'ramidal  decussation  and 
the  isolated  head  of  the  anterior  columna.  It  is  concerned  with  the  production  of 
the  ocular  and  pupillary  reflexes,  of  which  circuits  it  forms  the  central  division. 

(c)  The  rubrospinal  or  prepyramidal  tract,  also  called  Monakoiv's  bundle.  It 
is  triangular  in  outline  and  is  situated  anterior  to  the  crossed  pyramidal  tract. 
Its  fibers  may  be  traced  from  the  red  nucleus,  a  group  of  cells  situated  in  the  midbrain 
anterior  to  the  nucleus  of  the  third  nerve.  Shortly  after  their  origin  they  cross  the 
midline  of  the  body  and  descend  through  the  pons,  medulla  and  cord  to  the  level  of 
the  lumbar  region,  where  they  arborize  around  the  cells  of  the  posterior  extent  of  the 
anterior  horn.  This  tract  appears  to  be  an  adjunct  of  the  pyramidal  system, 
because  the  red  nucleus  is  connected  with  the  cerebrum  and  cerebellum. 

(d)  The  vestibulospinal  tract  is  composed  of  descending  fibers  which  are  scattered 
through  the  anterior  funiculus  in  the  immediate  vicinitj^  of  the  root  fibers.  They 
arise  in  the  lateral  vestibular  nucleus  (Deiters')  in  the  medulla  and  terminate  in 
the  spinal  gray  matter.  It  may  be  inferred,  therefore,  that  this  tract  constitutes 
an  important  transmitting  system  between  the  cerebellum  and  the  cord,  being 
directly  concerned  with  the  adjustment  of  the  musculature  to  sensory  stimuli  from 
the  semicircular  canals. 

(e)  The  olivospinal  tract  or  bundle  of  Helweg.  It  is  a  small  tract  and  is  situated 
near  the  surface  of  the  cord  just  lateral  to  the  anterior  roots.  Its  fibers  are  said  to 
arise  in  the  thalamus  and  to  extend  through  the  inferior  olive  of  the  medulla  as  far 
as  the  lower  cervical  region. 

(J)  The  comma  tract  of  Schultze  is  situated  in  the  posterior  funiculus  of  the 
cervical  and  upper  thoracic  regions.  It  occupies  the  anterior  realm  of  the  column 
of  Burdach,  and  appears  to  be  formed  by  the  descending  branches  of  the  posterior 
root  fibers.  Many  of  the  latter  divide  into  ascending  and  descending  branches  and 
thus  connect  afferently  with  different  levels  of  the  cord.  For  this  reason,  they 
cannot  be  regarded  as  forming  true  descending  tracts.  A  similar  origin  is  ascribed 
to  Lissauer's  bundle  which  embraces  the  tip  of  the  posterior  horn,  as  well  as  to  the 
oval  field  of  Flechsig  and  the  median  triangle  of  Gombault  and  Philippe. 

(g)  The  septomarginal  bundle  is  oval  in  shape  and  borders  upon  the  posterior 
median  fissure.  It  contains  short  fibers,  but  has  been  said  to  embrace  also  certain 
fibers  from  the  midbrain. 

2.  Ascending  Tracts. — (a)  The  posterior  tracts  occupy  the  fasciculi  gracilis  and 
cuneatus,  and  are  formed  almost  wholly  by  the  axones  of  the  cells  situated  in  the 
ganglia  of  the  spinal  roots.  Several  of  them  also  arise  from  different  segments  of 
the  spinal  gray  matter.  The  former  are  characterized  as  exogenous  and  the  latter 
as  endogenous;  moreover,  while  some  of  these  fibers  terminate  at  different  levels 
of  the  gray  matter,  others  extend  through  the  entire  length  of  these  columns  and 
eventually  end  in  the  nucleus  gracilis  and  nucleus  cuneatus  of  the  medulla.  The 
former,  very  clearly,  are  spinal  associative  in  their  function,  while  the  latter  belong 
to  the  projection  system  and  form  a  part  of  the  afferent  side  of  this  cerebral  con- 
ducting path.     During  their  course  through  the  cord,  these  fibers  remain  on  the  side 

1  Rothmann,  Zeitschr.  f.  klin.  Med.,  xlviii,  and  Schafer,  Quart.  Jour,  of  Exp. 
Physiol.,  iii,  1910,  355. 


THE    SPINAL   CORD    AS    A    CONDUCTING    PATH 


(317 


on  which  thej'  have  arisen,  but  finally  cross  the  median  Hne  l)y  way  of  the  sensory 
decussation  of  the  medulla.  It  is  also  to  be  noted  that  the  fibers  whi(-h 
have  their  origin  at  a  low  level,  are  gradually  pushed  toward  the  median  fissure 
by  those  fii)er3  which  enter  at  hip;lu'r  levels,  and  naturally,  as  this  displacement 
affects  the  exoRcnous  fibers  only,  the  upper  thoracic  and  cervical  segments  of  the 
fasciculus  gracilis  gradually  assume  the  character  of  the  conducting  path  for  the 
root  fibers  of  the  lumbar  and  sacral  regions. 


cerebral 


cortex 


trigeminal   lemniscus 
sKin 


Tnediol  lemniscus 


nucleus  of  dorsal 

funiculus 


spinal  lemniscus 


venTrol  py ramida 
Tract 


dorsal  funiculus 
ateral  pyramidal  fracT 
spinal  ^an^lion 
sKin 

muscle 

Fig.  306. — Diagram  of  the  Chief  Conn-ections  Between*  the  Spinal  Cord  and  the 

Cerebral  Cortex. 
The  spinal  lemniscus  complex  carries  the  ascending  exteroceptive  systems  (touch, 
temperature,  and  pain) ;  the  dorsal  funiculus  and  medial  lemniscus  complex  carry 
chiefly  ascending  proprioceptive  impulses  (a  nerve  of  muscle  sense  is  the  only  member 
of  this  group  included  in  the  drawing).  The  diagram  also  shows  the  sensorj^  path  from 
the  skin  of  the  head  to  the  cerebral  cortex  through  the  V  cranial  nerve  (trigeminus) 
and  the  trigeminal  lemniscus.  The  pyramidal  tract  (tractus  corticospinalis)  is  the 
common  descending  motor  path  for  both  exteroceptive  and  proprioceptive  nervous 
impulses  from  the  cerebral  cortex.     (Herrick.) 


(b)  The  direct  or  spinocerebellar  tract  (Flechsig's)  is  one  of  the  two  best  known 
tracts  in  the  lateral  funiculus.  As  its  fibers  arise  in  the  cells  of  Clark's  column, 
thej^  are  endogenous  in  character,  and  serve  for  the  inward  conduction  of  those 
impulses  which  have  attained  the  aforesaid  cells  bj-  w-aj'  of  certain  fibers  of  the 
posterior  root.  \Miile  most  of  them  enter  the  inferior  peduncle  of  the  cerebellum 
and  terminate  in  the  posterior  and  median  areas  of  the  vermiform  lobe,  some  also 


618 


THE    FUNCTION   OF   THE    SPINAL    CORD 


pass  into  the  gray  matter  of  the  upper  spinal  cord.     The  cerebellar  groups  remain 
largely  uncrossed. 

(c)  The  superficial  anterolateral  tract  (Gower's). — The  origin  of  these  fibers  in 
the  lower  spinal  gray  matter  and  their  distribution  to  the  cerebellum  and  related 
parts  suggest  that  they  convoy  afferent  impulses  from  the  posterior  roots  to  the 
cerebellum,  1  and  hence,  their  function  must  be  similar  to  that  of  the  fibers  of 
Flechsig's  tract.  They  are  concerned  with  the  coordination  of  muscular  move- 
ments, their  immediate  purpose  Joeing  to  aid  in  the  conduction  of  the  impulses  from 
the  receptors  in  the  muscles,  tendons  and  joints  to  the  coordinating  organ,  the  cere- 


FiG.  307. — Diagram  of  the  Spinocerebellar,  Bulbotegmental,  Cerebellotegmental, 

PONTOTEGMENTAL,  AND  PONTOCEREBELLAR  TRACTS. 

OT,  Optic  thalamus;  F,  fillet;  RN,  red  nucleus.      {After  v.  Gehuchten.) 


bellum.  For  this  reason,  they  may  be  regarded  as  forming  a  part  of  the  afferent 
arc  required  for  the  production  of  the  muscle  sense  and  coordination  of  muscular 
action.  That  this  is  true  may  also  be  gathered  from  the  fact  that  the  division  of 
this  tract  is  followed  by  a  moderate  degree  of  atonia  and  ataxia-  below  the  seat  of 
the  lesion. 

(d)  The  spinothalamic  and  spinotectal  tracts  are  really  a  part  of  Gower's  tract. 
These  fibers  traverse  the  medulla  and  pons  and  terminate  very  largely  in  the  optic 

^  Bruce,  Quart.  Jour,  of  Exp.  Physiol.,  iii,  1910,  391;  also  see:  Lewandowsky, 
Untersuchungen  viber  die  Leitungsbahnen  d.  Truncus  cerebri,  etc.,  Jena,   1904. 

2  Bing,  Archiv  fiir  Physiol,  1906,  250;  also  see:  Horsley  and  Macnalty,  Brain, 
1909,  237. 


THE    SPINAL    CORD    AS    A    CONDUCTING    PATH  619 

thalamus  of  the  same  side  but  iti  jwrt  also  in  the  corpora  quadriKomina  of  both 
sides. 

(e)  A  few  scattered  bundles  of  asceiidiii^  fil)ers  are  also  found  in  the  anterior 
funiculus.  They  intermingle  here  with  the  deseendins  tracts  mentioned  previously. 
The  fasciculi  proprii  or  ground  bundles  are  not  mentioned  separately  in  this  enu- 
meration, because  parts  of  tliem  have  already  been  described  under  the  heading 
of  the  septomarginal  and  connna  tracts. 

The  Function  of  the  Roots  of  the  Spinal  Cord.  The  Bell-Magendie 
Law.' — The  general  conclusion  to  be  derived  from  the  preceding 
discussion  is  that  the  white  matter  of  the  spinal  cord  of  the  higher 
animals  is  arranged  in  definite  tracts  which  connect: 

(a)  Different  segments  of  this  structure  with  one  another,  thus 
forming  the  propriospinal  paths,  i.e.,  a  short  or  reflex  system  of 
conduction. 

(b)  The  cord  with  the  hindbrain,  midbrain  and  forebrain,  forming 
a  long  or  projection  system  of  conduction.  With  the  hindbrain  the 
connections  are  made  over  the  posterior  cerebellar  tracts,  the  tracts 
of  Goll  and  Burdach,  the  spino-olivary  and  vestibulospinal  bundles. 
The  midbrain  receives  its  impulses  by  way  of  the  spinotectal  tracts 
and  discharges  them  over  the  rubrospinal.  The  forebrain  (thalamus) 
is  entered  through  the  spinothalamic  tracts.  From  here  the  impulses 
are  relegated  to  the  cerebrum,  which  organ,  as  has  been  stated  above, 
is  not  in  direct  afferent  communication  with  the  cord,  because  the 
impulses  directed  to  it  from  the  latter  structure,  are  first  relayed 
into  lower  nuclei  and  centers  before  they  are  finally  distributed  to  the 
cerebral  cortex.  On  the  efferent  side,  however,  the  cerebrum  is  in 
possession  of  a  direct  path  in  the  shape  of  the  anterior  and  lateral 
pyramidal  tracts.  As  has  been  emphasized  repeatedly,  the  mere 
entrance  of  an  impulse  into  the  cerebrum  does  not  admit  it  to  conscious- 
ness; in  fact,  many  of  the  reactions  resulting  in  consequence  of  cerebral 
activity  retain  their  reflex  character  as  strictly  as  those  evoked 
exclusively  with  the  help  of  the  spinal  cord.  It  is  true,  however, 
that  many  of  them  are  controlled  by  consciousness.  They  are  then 
converted  into  volitional  acts,  the  preceding  afferent  impulses  having 
been  received  in  consciousness  as  sensations  of  different  qualities. 

We  are  now  in  a  position  to  go  one  step  farther  and  to  inquire 
how  the  different  spinal  tracts  and  especially  those  belonging  to  the 
projection  system,  are  connected  with  the  distant  receptors  and  ef- 
fectors. It  will  be  remembered  that  each  spinal  nerve  arises  by  two 
roots,  an  anterior  or  ventral,  and  a  posterior  or  dorsal,  and  that  these 
roots  finally  unite  to  form  a  nerve.  Centrally  to  their  point  of  union, 
the  posterior  group  of  fibers  is  associated  with  a  colony  of  cells,  which 
form  the  so-called  intervertebral  ganglion.  In  1811  Ch.  Bell^  found 
that  the  mechanical  stimulation  of  the  anterior  group  of  fibers  gives 
rise  to  movements,  while  the  posterior  behaves  negatively  in  this 

'  Longet,  Anat.  et  physiol.  de  la  syst.  nerv.,  1847. 

2  An  idea  of  a  new  anatomy  of  the  brain,  London,  1811. 


620  THE    FUNCTION    OF   THE    SPINAL    CORD 

regard.  In  1822  Magendic^  succeeded  in  demonstrating  that  the 
division  of  the  anterior  roots  destroys  motion,  while  the  section  of  the 
posterior  roots  produces  a  loss  of  sensation.  Owing,  however,  to  the 
fact  that  the  former  is  in  possession  of.  a  perfectl}^  local  sj^stem 
of  sensory  fibers  and  that  the  latter  is  connected  with  motor  reflex 
paths,  this  investigator  did  not  succeed  in  fully  establishing  their 
function.  This  end  was  finally  attained  by  Joh.  v.  MuUer  as  a  result 
of  his  experiments  upon  tlu^  spinal  roots  of  the  frog. 

In  its  modern  form  the  Bell-Magendie  law  holds  that  the  afferent 
impulses  from  the  superficial  and  deep  parts  of  the  trunk  and  ex- 
tremities are  conducted  into  the  cord  by  way  of  the  posterior  roots, 
while  the  efferent  impulses  to  these  parts  leave  this  structure  over  the 
fibers  of  the  anterior  roots.  Thus,  a  most  perfect  localization  of 
sensory  and  motor  function  is  had  in  this  region  of  the  nervous  system. 
To  prove  this,  we  may  resort  to  the  methods  of  division  and  stimulation, 
as  follows: 

1.  Section: 

(A)  Anterior  root:  loss  of  motion  in  the  regions  supplied  by  this  nerve. 

(B)  Posterior  root:  loss  of  sensation  (contralateral)  in  the  region  innervated  by 
this  nerve  (ataxia  and  loss  of  reflex  movements). 

2.  Stimulation: 

(A)  Anterior  root: 

(o)  Distal  end :  motor  results  of  the  kind  ordinarily  produced  by  this  nerve. 
(6)  Central  end :  no  motor  results,  but  retrogressive  sensation. 

(B)  Posterior  root: 

(a)  Distal  end :  no  results. 

(b)  Central  end :  sensations  of  the  kind  ordinarily  conveyed  by  this  nerve. 

In  its  complete  form  the  Bell-Magendie  law  also  takes  cognizance 
of  certain  minor  facts  which  are  as  follows:  It  has  been  mentioned 
above  that  the  anterior  root  as  such  is  not  devoid  of  sensation  and 
hence,  does  not  differ  in  this  regard  from  other  tissues.  For  this 
reason  its  excitation  must  give  rise  to  "retrogressive"  sensory  impulses 
which  are  purely  local  in  their  origin,  and  should  therefore  be  sharply 
differentiated  from  those  which  arise  at  the  periphery  and  attain 
consciousness  by  way  of  the  posterior  group  of  fibers.-  In  the  second 
place,  as  the  sensory  impulses  traversing  the  posterior  roots  also  in- 
clude those  which  help  in  the  formation  of  the  muscle-sense,  the  divi- 
sion of  these  fibers  must  necessarily  be  followed  by  a  certain  degree 
of  ataxia;  in  other  words,  in  the  absence  of  the  sensory  impressions 
from  the  muscles  and  tendons,  the  muscular  movements  must  lose 
their  coordinated  character.  In  the  third  place,  it  should  be  re- 
membered that  the  stimulation  of  the  central  end  of  the  divided 
posterior  root  may  also  give  rise  to  movements,  but  these  occasional 
motor  effects  are  reflex  in  their  nature  and  cease  immediately  after  the 
division  of  the  anterior  roots.  Being  desirous  of  simplifying  this  topic 
as  much  as  possible,  I  refrain  at  this  time  from  a  discussion  of  certain 

1  Jour,  de  Physiol,  ii,  1822,  276. 

2  CI.  Bernard,  Lemons  sur  la  physiol.  et  la  path,   du  syst.  nerveaux,  i. 


THE    SPINAL    CORD   AS   A    CONDUCTING    PATH 


621 


other  facts  which,  however,  do  not  put  the  general  applical)ihty  of 
this  hiw  ill  question.  I  also  oinit  for  the  present  the  structural  and 
functional  relationship  existing  between  the  spinal  cord  and  the 
sjnnpathetic  system.  We  shall  see  later  on  that  the  anterior  roots  also 
contain  efferent  fibers  for  the  autonomic  organs  and  that  these  in  turn 
send  impulses  to  central  parts  by  way  of  the  rami  communicantes 
and  the  posterior  roots. 

The  Trophic  Function  of  the  Spinal  Cord.  The  Wallerian  Law 
of  Degeneration. — It  has  been  discovered  Ijy  Nasse^  that  a  nerve- 
fiber,  when  disconnected  from  its  cell-body,  undergoes  certain  very 
characteristic  alterations  in  its  structure.     In  applying  this  fact  to 


^ 


Fig.  308. 


Fig.  309. 


Fig.  308. — Schema  to  Show  the  Course  of  the  Degeneration  Following  the 
Division  of  the  Roots  of  the  Spinal  Cord. 

A,  Division  of  the  anterior  root;  B,  division  of  the  posterior  root  distally  to  spinal 
ganglion;  C,  division  of  the  posterior  root  centrally  to  spinal  ganglion.  The  degen- 
erated portions  are  indicated  in  solid  black. 

Fig.  309. — Schema  Illustrating  the  Course  of  Degeneration  in  Motor  and 
Sensory  Neurons. 

A,  Motor  neuron  of  the  anterior  root;  B  and  C,  sensory  neurons  of  the  posterior 
root.  The  portion  separated  from  the  cell  degenerates,  as  is  indicated  by  the  dotted 
lines. 

the  spinal  nerves,  A.  Waller-  succeeded  in  demonstrating  that  a  cut 
made  distally  to  the  intervertebral  ganghon,  leads  to  a  degeneration 
of  both  roots  in  an  outward  direction,  involving  finally  the  entire 
nerve  as  far  as  its  end-organs  (secondary  degeneration).  Quite 
similarly,  it  was  shown  that  the  division  of  the  spinal  roots  centrally 
to  this  ganglion  gives  rise  to  degenerative  changes  which  pursue 
a  course  in  opposite  directions  from  the  seat  of  the  lesion,  t'.e.,  the 
anterior  root  degenerates  toward  the  periphery   and    the    posterior 

1  Mviller's  Archiv,  1839,  405. 

2  Compt.  rend.,  Acad,  des  sciences,  xxxiv,  1852. 


622  THE    FUNCTION    OF   THE    SPINAL   CORD 

root  toward  the  cord.  The  deduction  immediately  to  be  derived 
from  these  facts,  is  that  the  trophic  center  (cell-bodies)  of  the  fibers 
composing  the  former,  is  situated  in  the  spinal  cord,  while  that  of  the 
posterior  root  fibers  lies  in  the  ganglion  with  which  this  root  is  associ- 
ated. Having  been  told  previously  that  the  efferent  fibers  composing 
the  anterior  root  originate  in  the  ganglion  cells  of  the  gray  matter  of  the 
anterior  horn,  and  that  the  afferent  fibers  of  the  posterior  root  are  derived 
from  the  cells  of  the  spinal  gangha,  we  are  now  able  to  localize  the 
degeneration  in  these  neurons  in  the  manner  indicated  by  Fig.  309. 
It  might  be  mentioned  that  the  descending  type  of  degeneration,  ob- 
served in  anterior  poHomyehtis,  is  represented  by  neuron  A  of  this 
figure,  because  it  is  commonly  accepted  that  the  active  agent  of  this 
disease  destroys  the  cells  of  the  anterior  horn,  and  thus  produces  a 
functional  uselessness  of  the  corresponding  nerve  fibers  and  motor 
organ.  A  degeneration  very  similar  to  that  represented  by  neuron 
C,  occurs  in  the  course  of  tabes  dorsalis,  or  locomotor  ataxia.  In  this 
disease  the  lesion  remains  localized  at  first  in  the  terminals  of  the  pos- 
terior root  fibers  with  the  result  that  the  muscle  and  tendon  sense  is 
rendered  defective,  thereby  preventing  the  proper  coordination  of 
muscular  movements. 

These  facts,  however,  do  not  justify  us  in  recognizing  the  existence 
of  special  neurons  with  an  exclusive  trophic  function,  because  the 
nutrition  of  a  tissue  is  dependent  primarily  upon  its  activity,  and  the 
latter  in  turn  upon  the  excitatory  and  regulatory  power  of  the  nerve 
cells.  Thus,  an  injury  to  these  nervous  elements  invariably  leads  to 
trophic  disturbances  in  the  tissues  even  without  their  being  equipped 
with  special  trophic  quahties.  For  this  reason,  we  find  that  the  skele- 
tal muscles  atrophy  when  separated  from  their  ganglion  cells.  Ex- 
ceptions to  this  rule  are  few  in  number  and  are  referable  to  the  fact  that 
some  muscles,  such  as  the  sphincter  ani,  are  not  under  the  direct 
control  of  the  central  nervous  system.  Upon  this  basis,  we  are 
also  able  to  explain  the  trophic  disturbances  which  are  frequently 
observed  in  the  course  of  degenerating  afferent  nerves  (Fig.  309,  B). 
Thus  it  is  found  that  the  inflammation  of  the  ganglia  upon  the  posterior 
roots  leads  to  the  condition  of  herpes  zoster  ("shingles")  in  the  area 
from  which  the  corresponding  fibers  are  derived.^  The  skin  may  also 
become  glossy  and  desquamate,  which  condition  may  eventually  give 
rise  to  a  loss  of  the  hair  and  nails,  or  to  a  formation  of  ulcers.  In- 
clusive of  this  trophic  influence,  the  functions  of  the  spinal  cord  may 
therefore  be  summarized  as  follows: 

(o)  It  is  an  important  seat  of  reflex  action. 

(b)  It  forms  one  of  the  principal  conducting  paths. 

(c)  Its  centers  are  automatically  active  and  give  rise  to  the  tonicity  of  the 
musculature. 

(d)  It  regulates  the  activity  and  trophic  condition  of  the  tissues  and  plays  an 
important  part  in  the  heat  production  of  our  body. 

1  Head  and  Campbell,  Pathology  of  Herpes  Zoster,  Brain,  xxiii,  1901,  353. 


THE    SPINAL   COIID    AS    A    CONDUCTING    PATH 


023 


The  Distribution  of  the  Impulses  Derived  from  the  Posterior 
Roots. — The  posterior  roots  of  the  cord  are  very  iinpcjrtiuit  "feeders" 
of  the  central  nervous  sytcm.  Together  with  the  afferent  fibers  of 
the  cranial  nerves,  they  constitutci  the  only  means  by  which  the  higher 
centers  may  l)e  influenced  by  impulses  generated  peripherally.  These 
impulses  em])race  first  of  all  the  superficial  and  deep  sensations  of 
touch,  pain  and  temperature,  as  well  as  those  derived  from  the  re- 
ceptors in  the  muscles  and  tendons,  having  to  do  with  the  muscle- 
sense.     On  their  arrival  in  the  terminals  of  the  posterior  root  fibers, 

Eomolalcral  imptihra  underli/in/j  muteutar  setuibilihj—i.e.  tetue  oj  patiive  position  and  of 
viovemcnl,  also  nj  touch  and  preeewc  Jot  a  Jew  ttgrncnln. 


6.  Homolateral 
unconscious 


7.  BtUrdUuereU 

iincOtttciout  ajjerertt 
impuUa  undcrlijiruj 
j  muse.  Co-ordination 
I    and  refiex  lone. 


8.  All  impuliet 
oJ  pain,  oJ  heat, 
and  oJ  cold 
(Uttcrolaleral). 


9.  Uelerolateral  impuUea  oJ 
touch  and  pre^Bure^ 

Fig.  310. — Dl^-GRam  to  Illustrate  the  Termination  of  Peripheral  Afferent 
Fibers  in  the  Spinal  Cord,  and  the  Origin  of  the  Secondaky  Central  Paths,  with  a 
Brief  Summary  of  Their  Function. 

1,  Bundles  of  fibers  passing  up  in  the  posterior  column — many  myelopetal  (to  sp. 
cord)  and  the  remainder  bulbopetal  (to  p.  col.  nuclei) ;  2,  fibers  terminating  around  the 
cells  of  Clarke's  column;  3,  fibers  arborizing  around  cells  in  the  posterior  horn,  and  inter- 
mediate gray  matter;  4,  ditto  around  the  anterior  horn-cells;  5,  ditto  swerving  into  the 
lateral  column  to  neighboring  gray  matter;  6,  direct,  or  dorsal  spinocerebellar  tract; 
7  and  8,  Gowers'  tract,  i.e.  (7)  ventral  spinocerebellar  tract;  (8)  spinothalamic  and 
tectal  tracts;  9,  ascendingtract  in  the  anterior  column.     (Starling  after  W.  Page  May.) 


they  are  distributed  to  those  particular  groups  of  cells  and  fibers 
which  are  directly  concerned  with  their  conduction  to  other  parts. 
Their  distribution  is  effected  as  follows: 

(A)  Impulses  Retained  at  the  Level  of  their  Entrance  into  the  Cord. — They  are 
reflex  in  their  nature  and  gain  the  corresponding  effector  by  way  of  the  anterior 
root  fibers.  This  transfer  of  the  afferent  impulses  into  efferent  ones  is  accomplished 
directly  through  the  intervention  of  the  cells  of  the  anterior  and  lateral  horns  of  the 
neighboring  gray  matter.  While  the  largest  number  of  these  impulses  remain 
confined  to  the  same  side  of  the  cord,  some  also  seek  the  opposite  spinal  gray  matter 
and  opposite  anterior  root  by  way  of  the  posterior  white  commissure. 

{B)  Impulses  Seeking  Levels  above  and  below  their  Level  of  Entrance. — They  are 
distributed  to : 


624  THE    FUNCTION    OF    THE    SPINAL    CORD 

(o)  Higher  or  Lower  Segments  of  the  Cort/.— These  are  also  reflex  in  character, 
but  involve  the  spinal  sray  matter  and  anterior  roots  of  segments  situated  above 
or  below  the  point  of  their  entrance.  These  segments  are  reached  over  the  filjers 
of  the  ground  bundles  or  by  way  of  the  terminals  and  collaterals  of  the  fi})ers  of 
the  posterior  columns.  In  the  latter  case,  they  are  not  relayed,  because  many  of 
the  fibers  of  the  posterior  roots  divide  inside  the  cord  into  an  upper  and  a  lower 
branch,  the  former  eventually  arborizing  at  a  higher  and  the  latter  at  a  lower  level 
than  their  point  of  bifurcation.  The  connection  between  the  terminals  of  this 
afferent  fiber  and  the  anterior  gray  matter  is  effected  in  either  case  in  the  manner 
just  described. 

{}))  Higher  Centers  in  the  Cerebellum  and  Cerebrurn.— The  cerebellar  impulses 
are  concerned  with  the  muscle-sense  and  the  coordination  of  muscular  movements. 
They  are  transferred  from  the  posterior  root  to  posterior  cells  and  subsequently 
to  the  cerebellar  tracts  in  the  lateral  funiculus  and  the  cerebellum.  Some  of  these 
are  no  doubt  transferred  directly  to  efferent  channels,  while  others  pass  from  this 
organ  to  the  cerebrum,  where  they  may  either  enter  consciousness  or  remain  sub- 
conscious. They  then  seek  the  efferent  tracts  by  way  of  the  motor  areas.  The 
cerebral  impulses  leave  the  fibers  of  the  posterior  roots  and  enter  either  the  pos- 
terior tracts  or  those  of  the  lateral  funiculus.  Inasmuch  as  no  separate  tract  is 
set  aside  for  them  by  means  of  which  they  could  reach  the  cerebrum  directly, 
they  are  relayed  in  the  medulla  and  basal  ganglia  to  secondary  bundles  of  fibers. 
These  impulses  serve  conscious  and  subconscious  reactions.  In  the  first  instance, 
they  enter  consciousness  as  sensations  of  touch,  pain  and  temperature. 

Nothing  further  need  be  said  regarding  the  afferent  impulses  of 
touch,  pain  and  temperature,  when  concerned  with  reflex  action. 
Their  course  has  been  mapped  out  above  under  the  headings  of  A 
and  B,  a.  Much  controversy,  however,  has  arisen  as  to  their  course 
when  they  enter  consciousness,  and  give  rise  to  their  respective  sen- 
sations which  are  then  followed  by  voluntary  reactions.  This  con- 
troversy finds  its  origin  in  the  diversity  of  the  symptoms  following 
lesions  of  the  posterior  and  lateral  fasciculi.  Thus,  it  has  been  ob- 
served that  the  posterior  tracts  may  be  divided  in  lower  animals 
without  destroying  the  sense  of  touch.  Cases  have  also  been  recorded 
of  persons  with  extensive  lesions  of  the  same  columns  whose  sense  of 
touch  was  not  seriously  impaired.  But  this  evidence  does  not  prove 
that  the  tactile  impulses  do  not  enter  the  posterior  tracts  at  all,  but 
merely  suggests  that  two  paths  are  open  to  them,  namely,  the  long 
projection  fibers  of  the  posterior  funiculus  and  the  short  fibers  of  the 
lateral  funiculus.  Thus,  if  the  former  fibers  are  destroyed,  these  im- 
pulses are  still  able  to  gain  the  cerebrum  by  way  of  the  latter.  This 
view,  however,  is  not  fully  in  accord  with  the  results  of  experiments 
upon  lower  animals,  but  is  in  agreement  with  the  symptoms  presented 
by  persons  suffering  from  certain  affections  of  the  spinal  cord.  While 
this  matter  cannot  be  definitely  decided  at  the  present  time,  it  appears 
that  these  differences  are  chiefly  dependent  upon  the  fact  that  the 
spinal  paths  vary  somewhat  even  among  the  mammals. 

If  we  confine  ourselves  to  man,  we  may  draw  the  conclusion 
that  the  impulses  of  touch  and  pressure  are  transmitted  under  normal 
conditions  to  the  posterior  tracts  of  the  same  side,  })ut  may  be  trans- 
ferred in  the  upper  cord  to  the  opposite  anterolateral  columns.     Head 


THE    SPINAL    CORD    AS    A    CONDUCTING    PATH  625 

and  Thompson^  have  elucidated  this  matter  further  by  dividing  the 
sense  of  touch  into  tactile  discrimination  and  tactile  localization.  The 
former  term  is  employed  to  designate  the  ability  of  being  able  to 
discriminate  between  two  mechanical  stimuli  applied  simultaneously 
to  the  skin.  This  sensation  may  be  evoked  most  easily  by  touching  the 
integument  with  a  compass  the  points  of  which  have  been  separated 
from  one  another.  Tactile  localization  is  the  ability  accurately  to 
designate  the  area  which  has  been  stimulated.  In  certain  spinal 
diseases,  these  two  forms  of  touch  sensation  have  been  found  to  be 
dissociated.  The  former  was  lost,  while  the  latter  persisted.  In 
explanation  of  this  phenomenon,  it  is  held  that  the  fibers  allotted  to 
touch  discrimination,  are  contained  in  the  posterior  tracts  of  the  same 
side,  while  those  conveying  the  impulses  of  touch  proper,  are  included 
in  the  anterolateral  fasciculi  and  cross  the  median  line  below  the 
medulla. 

In  addition  to  this  dissociation  of  the  tactile  impressions  into 
touch  discrimination  and  touch  localization,  the  cutaneous  sensations 
may  also  be  divided  into  two  groups,  namely,  those  of  touch  and  those 
of  pain  and  temperature.  The  former  impulses,  as  we  have  just  seen, 
select  in  part  the  posterior  columns,  while  the  latter  appear  to  enter 
the  cells  of  the  posterior  gray  matter,  whence  they  attain  the  tracts 
of  the  opposite  anterolateral  fasciculi.  The  evidence  which  may  be 
submitted  in  support  of  this  view,  is  the  fact  that  in  syringomyeHa  the 
sensations  of  touch  and  pressure  are  retained,  while  those  of  pain  and 
temperature  are  lost.  In  other  words,  the  patient  exhibits  an  anal- 
gesia and  thermo-anesthesia  below  the  seat  of  the  lesion.  These 
symptoms  are  suggestive,  because  this  disease  affects  chiefly  the  gray 
matter  of  the  cord,  causing  a  vacuolization  of  the  cells  and,  therefore, 
a  destruction  of  the  connection  between  the  posterior  roots  and  the 
anterolateral  fasciculi  of  the  same  and  opposite  sides.  It  would  seem, 
therefore,  that  the  loss  of  the  sensations  of  pain  and  temperature  is 
dependent  in  this  case  upon  the  fact  that  they  cannot  reach  their  desti- 
nation on  account  of  this  block  upon  the  path  usually  selected  by  them 
in  gaining  the  opposite  anterolateral  tract. 

The  impulses  serving  the  muscle-sense,  may  also  be  divided  into 
two  groups,  namely,  those  which  pass  directly  to  the  cerebellum  and 
always  remain  subconscious  and  those  which  are  relayed  to  the  cere- 
brum and  finally  involve  voHtion.  It  has  been  stated  above  that,  the 
former  select  the  anterior  and  posterior  cerebellar  tracts  of  the  lateral 
funiculus  of  the  same  side,  while  the  latter  ascend  in  the  posterior 
columns  of  the  same  side.  The  latter,  however,  cross  finally  to  the 
opposite  cerebral  hemisphere  by  way  of  the  optic  thalamus.  Our 
muscular  movements  are  executed  in  accordance  with  the  character 
of  the  impulses  received  from  our  muscles  and  tendons.  This  regula- 
tion is  primarily  cerebellar,  but  may  be  modified  by  volition,  i.e.,  the 
activity  of  our  muscles  may  be  controlled  by  the  cerebellum  and  cerebrum 

1  Brain,  1906;  also  see:  Saunders,  Brain,  xxxvi,  1913,  166. 

40 


626  THE    FUNCTION    OF   THE    SPINAL    CORD 

either  without  or  with  the  help  of  consciousness,  especially  of  volition. 
In  the  first  case,  the  control  is  involuntary  or  reflex,  and  in  the  second, 
volitional  and  based  upon  an  accurate  conception  in  consciousness  of 
the  state  of  contraction  of  our  muscles  and  of  the  position  of  our  limbs. 
The  Effects  of  Hemisection  of  the  Spinal  Cord.^ — The  symptoms 
following  the  division  of  one-half  of  the  spinal  cord,  are  homolateral 
and  contralatei'al  in  their  nature,  i.e.,  they  may  or  may  not  be  con- 
fined to  the  side  of  the  lesion. 

A.  Homolateral: 

(a)  Motor  paralysis,  affecting  (o)  the  skeletal  muscles  innervated  by  the  efferent 
fibers  which  leave  the  cord  below  the  level  of  the  section,  and  (6)  the  smooth 
musculature  of  the  blood-vessels.  The  latter  is  made  evident  by  the  injection 
of  the  blood-vessels  of  the  parts  affected  and  the  consequent  rise  in  tempera- 
ture. The  skin  becomes  dry  which  fact  points  toward  a  secretory  motor 
paralysis. 

(6)  Sensory  paralysis  (anesthesia)  in  the  region  of  those  afferent  fibers  which 
enter  directly  at  the  seat  of  the  injury.  This  zone  is,  of  course,  limited.  Loss 
of  the  muscle-sense  and  tactile  discrimination.  The  other  parts  show  a  cer- 
tain degree  of  hyperesthesia. 

B.  Contralateral: 

(a)  Motor  paralysis,  negative. 

(6)  Sensory  .paralysis,'  affecting  pain,  temperature  and  tactile  localization  in 

the  region  innervated  by  those  fibers  which  have  crossed  below  the  level  of 

the  lesion. 

This  syndrome,  consisting  of  unilateral  loss  of  motion  and  contra- 
lateral loss  of  sensation,  is  not  very  evident  in  the  lower  animals,  but 
this  need  not  surprise  us,  because  the  localization  of  conduction  in  the 
simple  spinal  cords  differs  somewhat  from  that  found  in  the  human 
cord.^  In  addition,  we  are  confronted  here  by  the  difficulty  that  an 
animal  cannot-  interpret  sensory  disturbances  for  us. 

^  Brown-Sequard,  Jour,  de  Physiol.,  vi,  1863,  124;  also  see:  Petren,  Archiv  fiir 
Psychiatrie,  xlvii,  1911,  495. 

2  Karphus  and  Kreidl,  Pfliiger's  Archiv,  clviii,  1914,  275. 


SECTION  XVI 
THE  AUTONOMIC  NERVOUS  SYSTEM 


CHAPTER  LI 
THE  SYMPATHETIC  AND  PARASYMPATHETIC  SYSTEMS 

General  Arrangement. — It  has  been  stated  above  that  the  nervous 
system  consists  of  a  central  and  a  peripheral  division,  and  that  the 
latter  in  turn  is  built  up  of  (a)  the  cranial  and  spinal  nerves,  and  (6) 
the  ganglia  and  nerves  of  the  sympathetic  system.  The  term  sympa- 
thetic, however,  is  somewhat  misleading,  because,  as  originally  em- 
ployed, this  system  included  merely  those  ganglia  which  are  situated 
along  the  spinal  cord,  beginning  above  with  the  superior  cervical  and 
ending  below  with  the  coccygeal.  Its  function  was  said  to  be  the 
regulation  of  the  activities  of  the  internal  organs  or  viscera.  In  the 
course  of  time  a  number  of  ganglia  have  also  been  found  which,  al- 
though innervating  the  viscera,  do  not  occupy  a  position  within  the 
realm  of  the  sympathetic  system  as  originally  mapped  out.  These 
are  said  to  form  the  so-called  parasympathetic  system.  On  account 
of  this  conflict,  Langley '  has  advocated  the  use  of  the  more  general  term 
visceral  or  autonomic.  Hence,  in  its  modern  conception  the  autonomic 
nervous  system  is  composed  of  a  number  of  ganglia  and  plexuses  of 
nerves  which  are  rather  sharply  differentiated  from  the  cerebrospinal 
system  by  certain  anatomical,  histological  and  physiological  character- 
istics. It  is  formed,  on  the  one  hand,  by  the  sympathetic  system  as 
originally  conceived  and,  on  the  other,  by  certain  ganglia  which  are 
situated  in  the  realm  of  the  cranial  and  sacral  nerves.  The  latter  are 
collectively  known  as  the  parasympathetic  system.  In  making  these 
distinctions  the  student  is  cautioned  not  to  regard  the  autonomic 
system  as  a  functional  curiosity,  or  to  separate  it  completely  from  the 
cerebrospinal  system,  because  it  forms  after  all  a  closely  correlated 
division  of  the  whole  nervous  mechanism. 

The  entire  autonomic  nervous  system  is  composed  of  a  series  of 
gangUa  which  are  scattered  through  the  regions  of  the  head,  neck, 
thorax,  abdomen  and  pelvis,  beginning  above  with  the  superior  cer- 
vical and  terminating  below  with  the  coccygeal  ganglion.  These  col- 
onies of  cells  are  united  by  nerve-fibers  which  are  frequently  augmented 
into  networks  or  plexuses.     It  consists  of: 

1  Ergebn.  der  Physiol.,  ii,  1903,  2,  and  Zentralbl.  fur  Physiol.,  xxvii,  1913,  149. 

627 


628 


THE    AUTONOMIC    NERVOUS    SYSTEM 


THE  SYMPATHETIC  AND  PARASYMPATHETIC  SYSTEMS         G29 

A.  The  si/mpathctic  chain,  situated  on  each  side  of  the  vertebral  cohimn  and  ron- 
sistint?  of  {j;aiifz;Ua  which  are  connected  by  strands  of  fibers.  It  is  divided  into  a: 
(a)  Ceruiail  portion  which  is  placed  along  the  neck  and  is  beset  with  the  superior, 

middle  and  inferior  cervical  ganglia.  This  delicate  string  of  non-medullated 
fibers  may  pursue  an  independent  course  along  the  carotid  artery  (rabbit) 
or  be  intermingled  with  the  niedullated  fibers  of  the  vagus  (dog). 

(6)  Thoracic  portion,  consisting  of  eleven  or  twelve  ganglia,  the  first  three  of 
which  are  united  into  the  large  ganglion  stellatum. 

(c)  Lumbar  portion,  embracing  the  three  or  four  ganglia  of  this  region. 

{d)  Sacrococcygeal  portion,  formed  by  an  equal  number  of  sacral  ganglia 
terminating  with  the  ganglion  coccygeum. 

B.  A  system  of  large  ganglia  which  may  be  grouped  as : 

(a)  Cranial,  for  example,  the  ganglion  ciliare  upon  the  third  nerve,  the  ganglion 
sphenopalatinum  upon  the  second  branch  of  the  trigeminus,  the  ganglion 
oticum  et  ganglion  submaxillare  upon  the  third  branch  of  the  same  nerve. 
The  vagus  and  glossopharyngeus  also  embrace  certain  fibers  which  connect 
with  the  sympathetic  system. 

(b)  Thoracic,  for  example,  the  plexus  cardiacus  upon  the  arch  of  the  aorta. 

(c)  Abdominal,  for  example,  the  plexus  Solaris,  embracing  the  right  and  left 
suprarenal,  the  superior  mesenteric,  the  celiac  and  certain  smaller  ganglia  in 
the  region  of  the  stomach.  The  greater  and  lesser  splanchnic  nerves  unite 
this  complex  with  the  thoracic  ganglia.  The  distalmost  ramifications  of  the 
sympathetic  system  in  this  region  form  the  plexuses  of  Meissner  and  Auerbach. 

{d)  Pelvic,  for  example,  the  ganglion  hypogastricum. 

Characteristics  of  the  Autonomic  Nervous  System. — The  preceding 
outline  teaches  us  that  the  autonomic  nervous  system  occupies  an 
anatomically  distinct  position;  in  fact,  its  gross  anatomical  charac- 
teristics are  such  that  we  are  tempted  to  regard  it  as  a  nervous  system 
within  a  nervous  system.  On  the  histological  side,  we  find  that  the 
sympathetic  cells  are  usually  multipolar,  rounded  in  outline,  and  some- 
what smaller  than  those  bslonging  to  the  cerebrospinal  structures. 
The  nerve-fibers  are  characterized  by  an  absence  of  the  myelin  sheath 
which  imparts  to  them  a  grayish  color.  The  only  exception  to  this 
rule  is  to  be  found  in  the  medullated  fibers,  forming  the  connection 
between  the  gray  matter  of  the  cerehrospinal  system  and  the  neighbor- 
ing sympathetic  ganglia.  These  bridges  of  fibers  are  known  as  the 
white  rami  communicantes.  On  the  physiological  side,  we  observe 
that  the  reactions  occurring  in  the  realm  of  the  sympathetic  system, 
are  for  the  most  part  subconscious.  This  implies  that  they  are  not 
under  the  direct  guidance  of  volition  and  are,  therefore,  typically 
reflex  in  their  character.  Besides,  as  they  are  relatively  independent 
of  the  central  nervous  system,  and  may  continue  even  after  the  de- 
struction of  the  latter,  they  are  usually  described  as  autonomic.  On 
the  pharmacological  side,  we  find  that  the  sympathetic  elements  behave 
in  a  very  characteristic  manner  toward  certain  drugs.  Nicotin  acts 
as  a  cell  poison,  i.e.,  it  paralyzes  the  synapses  and  thus  separates  the 
distal  from  the  central  neuron.  Efferent  impulses  are  in  this  way 
prevented  from  reaching  the  peripheral  motor  organ.  Adrenalin 
exerts  a  specific  action  upon  the  thoracic  and  lumbar  divisions  of  the 
sympathetic  system,  while  atropin,  muscarin  and  pilocarpin  are  said 


630 


THE    AUTONOMIC    NERVOUS    SYSTEM 


to  act  primarily  upon  the  paras^^npathetic  system,  and  chiefly  upon 
the  cranial  gangUa  and  their  ramifications. 

The  Function  of  the  Autonomic  System. — The  innervation  of  the 
striated  musculature  is  effected  b}'  fibers  which  arise  in  the  cerebrum, 
cerebellum  and  spinal  cord  and  pursue  a  perfectly  straight  course 
to  the  peripheiy.  Those  fibers,  on  the  other  hand,  which  are  con- 
cerned with  the  vegetative  processes,  do  not  pass  directly  to  the 
motor  end-organs,  but  are  fii-st  relayed  into  the  sjTnpathetic  system. 
The  latter,  therefore,  may  be  regarded  as  a  siding  upon  the  cerebro- 
spinal tract.  In  its  amplified  form  this  statement  signifies  that  the 
impulses  apportioned  to  striated  muscle  are  distinctly  cerebrospinal 
in  their  origin  and  remain  so  throughout  their  course,  while  those 


Fig.  312. — Cells  from  the  G.aa'gl.  Cervic.\le  Slpremum  of  Mast. 
-4.  and  B,  Cells  -vvith  short  dendrites;  C,  cell  with  long  dendrites;  a,  axon.      (Cajal.) 


distributed  to  smooth  and  cardiac  muscle  tissue,  as  well  as  to  the  glands, 
do  not  remain  so,  but  presently  assume  the  characteristics  of  the  auto- 
nomic or  sympathetic  system.  It  has  been  stated  above  that  the 
effectors  are  limited  in  nmnber,  because  only  two  structural  units 
enter  into  their  formation,  namely,  muscle  tissue  and  glandular  tissue. 
The  former,  however,  presents  itself  as  striated,  smooth  and  cardiac 
muscle.  We  now  observe  that  the  smooth  and  cardiac  muscle  tissues, 
together  with  the  glandular  tissue,  form  the  tj-pical  motor  organs 
of  the  autonomic  system,  w-hile  the  striated  muscle  alone  remains  dis- 
tinctly cerebrospinal  in  its  character. 

In  further  analysis  of  this  fact  it  becomes  immediately  apparent 


THE  SYMPATHETIC  AND  PARASYMPATHETIC  SYSTEMS         G31 

that  the  motor  units  of  the  autonomic  system  are  moulded  into  an 
array  of  end-organs  presenting  a  most  perplexing  structural  and  of 
functional  diversity.  Naturally,  all  of  them  are  concerned  with  vege- 
tative processes  and  as  such  give  rise  to  mov(!ments  as  well  as  to  se- 
cretions. The  former  embrace  the  musculomotor  effects  along  the 
alimentary  and  urinary  tracts,  the  vasomotor  and  pilomotor  actions, 
the  movements  of  the  iris,  and  others.  It  would  lead  us  altogether  too 
far  to  discuss  these  different  autonomic  functions  in  detail;  many  of 
them,  in  fact,  we  have  become  acquainted  with  in  the  course  of  our 
studies  upon  respiration,  the  circulation  of  the  blood  and  reflex  action. 
For  this  reason,  we  shall  confine  ourselves  at  this  time  to  a  more 
general  summary,  such  as  the  following: 

A.  The  Cranial  or  Parasympathetic  Sj/ste7ti. 

(a)  The  region  of  the  midbrain.  These  fibers  pass  through  the  nervus  oculo- 
motorius  and  end  in  the  gangl.  ciliare.  Motor  fibers  are  sent  to  the  muse, 
sphincter  pupiUte  and  muse,  ciliaris. 

(6)  The  region  of  the  bulb.  (1)  The  facial  nerve  conveys  fibers  to  the  gangl. 
sphenopalatinum  (nerv.  petrosus  superfic.  major),  whence  they  gain  the 
mucous  membrane  of  the  nose,  palate  and  upper  pharynx  as  well  as  the 
lacrimal,  submaxillary  and  sublingual  glands.  They  are  vasomotor  and 
secretomotor  in  their  function.  (2)  The  glossopharyngeus  contains  fibers 
for  the  gangl.  oticum  (nerv.  tympanicus  et  nerv.  petrosus  superf.  minor), 
whence  they  gain  the  parotid  gland.  They  are  vasodilator  and  secreto- 
motor in  their  function.  (3)  The  vagus  nerve  embraces  inhibitor  fibers  for 
the  heart,  motor  fibers  for  the  musculature  of  the  bronchi,  esophagus, 
stomach  and  intestine,  and  secretomotor  fibers  for  the  glands  of  the  stomach 
and  pancreas. 

B.  The  Cervical  Sympathetic  Syste?}}. 

1.  Musculomotor  fibers  for  the  muse,  dilator  pupilkr  and  the  smooth  muscle  tis- 
sue of  the  orbits  and  eyelids. 

2.  Vasomotor  fibers  for  the  blood-vessels  of  the  ears,  face,  conjunctiva,  iris, 
choroidea,  salivary  glands,  esophagus,  larynx,  thyroid,  and  brain. 

3.  Secretomotor  fibers  for  the  sweat  glands  of  the  head  region,  and  the  salivary 
and  lacrimal  glands. 

C.  The  Thoracic  Sympathetic  System. 
(o)  Vertebral  ganglia : 

1.  Vasomotor  fibers  for  the  skin  of  the  trunk  and  extremities. 

2.  Pilomotor  fibers  for  the  same  regions. 

3.  Secretomotor  fibers  for  the  sweat  glands  of  the  same  areas. 
(6)    Thoracic   and   abdominal   ganglia: 

1.  Musculomotor  fibers  for  the  heart  (gangl.  stellatum). 

2.  Vasomotor  fibers  for  the  abdominal  viscera  (splanchnic  s3-stem  and  solar 
ganglia). 

3.  Vasomotor  fibers  for  the  colon  descendens,  rectum,  bladder  and  uterus 
(gangl.  mesent.  inf.  and  nerv.  hypogastrici). 

D.  The  Sacral  Sympathetic  System  {Parasympathetic  in  Character) . 

1.  Musculomotor   fibers   for   the    colon   descendens,    rectum,    bladder   and 
genital  organs. 

The  Connections  between  the  Cerebrospinal  and  Autonomic 
Systems. — Inasmuch  as  the  vegetative  processes  are,  under  the 
direct  control  of  the  autonomic  system,  it  must  be  evident  that  those 
impulses  which  are  relegated  to  this  system  from  the  brain  and  cord, 


632  THE    AUTONOMIC    NERVOUS    SYSTEM 

must  leave  the  cerebrospinal  channels  and  enter  the  sympathetic 
ganglia.  This  transfer  is  accomplished  in  three  different  regions, 
namely,  by  way  of  the: 

A.  Cranial  nerves. 

(a)  Midbrain,  third  nerve  and  gangl.  ciliare. 

(b)  Bulb.      (1)  Second  branch  of  the  trigeminus,  gangl.  sphenopalatinum.      (2) 
Third  branch  of  the  trigeminus  and  gangl.  oticum  et  gangl.  submaxillare. 

(3)  Vagus    and    glo.ssopharj'ngeus. 

B.  Thoracic  and  hunbar  divisions  of  the  spinal  cord,  from  the  first  thoracic  to  the 
fourth    lumbar    nerves. 

C.  Sacral  division  of  the  spinal  cord,  over  the  nerv.  pelvicus. 

We  have  previously  seen  that  the  sympathetic  system  as  originally 
described,  consists  of  a  chain  of  ganglia  and  their  connections  situated 
along  the  vertebral  column  in  the  region  of  the  thoracic  and  lumbar 
segments  of  the  spinal  cord.  But  the  autonomic  system  also  includes 
a  number  of  ganglia  and  plexuses  which  do  not  belong  to  this  particu- 
lar region  of  the  nervous  system,  but  form  the  anatomically  distinct 
parasympathetic  system.  The  latter  embraces  the  cranial  and  sacral 
ganglia.  To  summarize,  the  autonomic  nervous  system  consists  of 
the  sympathetic  and  parasympathetic  systems.  The  latter  includes 
all  those,  ganglia  and  plexuses  which  are  not  directly  related  to  the 
thoracic  and  lumbar  divisions  of  the  spinal  cord.  A  glance  at  Fig.  311 
will  show  that  the  largest  number  of  the  viscera  receive  a  double 
nerve  supply,  namely,  one  from  the  sympathetic  system  proper  and 
one  from  the  parasympathetic  system.^  Peculiarly  enough,  the  func- 
tions of  these  two  groups  of  fibers  are  generally  antagonistic  to  one 
another.  In  illustration  of  this  statement  might  be  mentioned  the 
variations  in  the  size  of  the  pupil,  or  in  the  action  of  the  heart.  In 
the  former  case,  the  stimulation  of  the  oculomotor  nerve  representing 
the  autonomic  pathway  from  the  midbrain,  gives  pupillar  constriction 
and  the  excitation  of  the  cervical  sympathetic,  pupillar  dilatation. 
In  the  case  of  the  heart,  the  bulbar  autonomic  fibers  contained  in 
the  vagus  nerve,  are  cardio-inhibitory  in  their  function,  and  the  sym- 
pathetic, cardio-acceleratory. 

Having  found  that  the  cerebrospinal  and  autonomic  systems 
are  connected  by  definite  bridges  of  fibers,  let  us  for  a  moment  examine 
the  structural  details  of  one  of  these.  I  select  for  this  purpose  the 
spinosympathetic  rami,  because  their  course  has  been  made  out  with 
at  least  a  fair  degree  of  accuracy  (Fig.  313).  We  have  seen  that  the 
axons  of  the  cells  in  the  anterior  horn  seek  their  corresponding  motor 
end-organs  by  way  of  the  anterior  roots  (I).  In  tracing  these  fibers 
outward  to  the  point  where  they  intermingle  with  the  afferent  fibers 
tending  toward  the  posterior  root,  it  is  noted  that  a  numl)er  of  them 
leave  the  mixed  neiA^e  and  pursue  a  straight  course  toward  the  sympa- 
thetic ganglion  at  the  side  of  the  vertebral  column    (II    and    III). 

1  Gottlieb  and  Meyer,  Die  exper.  Pharmak.  als  Grundlage  der  Arzeneibehand- 
lung,    Berlin,    1912. 


THE  SYMPATHETIC  AND  PARASYMPATHETIC  SYSTEMS  (533 

These  fibers  retain  their  medullary  sheath  and  form  the  so-called  ramus 
all)us  c'oinmunicuns  (IF),  i.e.,  a  bridge  by  means  of  which  certain  effer- 
ent cerebrospinal  impulses  are  enabled  to  enter  the  sympathetic 
system  {S).  The  cell-bodies  of  these  neurons  form  the  lateromedian 
group  of  cells  of  the  anterior  horn  in  the  thoracic  and  lumbar  regions 
of  the  spinal  cord.  It  is  to  be  noted,  therefore,  that  the  anterior 
root  is  made  up  of  two  groups  of  efferent  fibers,  one  of  which  conveys 
impulses  directly  to  the  striated  muscles  and  the  other,  to  the  sympa- 
thetic system.  The  former  are  musculomotor  (striated  muscle)  in 
their  function,  and  the  latter,  musculomotor  (smooth  muscle)  vaso- 
motor, secretomotor  and  pilomotor. 


Fig.  313. — DiAGR.\iniATic  Representatiox  of  the  Connection  Betweex  the  Cerebro- 
spinal AND  Sympathetic  Systems. 
AR  and  PR,  Anterior  and  posterior  roots  of  the  spinal  cord;  SG,  spinal  ganglion; 
N,  spinal  nerve;  W,  white  ramus;  G,  gray  ramus;  <S,  sympathetic  ganglion;  /,  ordinary 
motor  neuron,  the  axon  of  which  pursues  a  straight  course  to  peripheral  effector; 
//,  motor  neuron,  the  axon  of  which  enters  sympathetic  ganglion  through  the  white 
ramus.  ///,  secondary'  neuron  carrj-ing  the  impulses  from  II  to  other  parts  of  sympa- 
thetic system;  IV,  secondarj^  neuron;  carrying  impulses  from  sympathetic  system 
through  the  gray  ramus  to  the  peripheral  effector  in  the  domain  of  the  cerebrospinal 
system;  T',  neuron  carrying  afferent  impulses  from  sympathetic  system  into  cerebro- 
spinal system  by  way  of  spinal  ganglion  and  posterior  root. 

Immediately  adjoining  the  ramus  albus  is  another  bridge  which 
unites  the  sympathetic  ganglion  with  a  somewhat  more  peripheral 
point  of  the  mixed  nerve.  Its  gray  color  suggests  that  the  fibers 
composing  it  are  non-meduUated  and  are,  therefore,  of  sympathetic 
origin.  This  is  the  ramus  griseus  communicans  (G).  In  some  animals, 
however,  the  white  and  gray  rami  are  united  into  a  single  trunk  and 
arise  from  the  same  segment  of  the  mixed  nerve  immediately  beside 
the  spinal  ganglion.  It  need  scarcely  be  emphasized  that  the  gray 
ramus  forms  an  afferent  connection  which  enables  sympathetic 
impulses  to  reach  the  spinocerebral  tracts  (IV  and  V). 


634  THE    AUTONOMIC    NERVOUS    SYSTEM 

At  the  hand  of  these  details,  we  are  now  in  a  position  to  explain 
why  typically  autonomic  functions  may  also  be  had  in  regions  which 
on  casual  observation  seem  to  be  innervated  exclusively  by  a  cerebro- 
spinal nerve.  Thus,  we  observe  that  vasomotor  and  secretomotor 
actions  are  not  restricted  to  the  viscera,  but  are  also  enacted  in  the 
integument  and  deeper  structures  of  the  trunk,  arms  and  legs.  It 
must  be  inferred,  therefore,  that  the  spinal  nerves  innervating  these 
parts,  derive  their  supply  of  sympathetic  fi])ers  ])y  way  of  the  gray 
rami  (IV).  In  this  way,  their  original  power  of  regulating  the  activity 
of  the  striated  musculature  is  augmented  by  the  control  of  the  smooth 
muscle  and  glandular  tissue.  To  illustrate,  the  sciatic  nerve  contains 
first  of  all  a  certain  number  of  fillers  for  the  skeletal  muscles  of  the 
leg,  secondly,  fibers  for  the  smooth  muscle  df  the  blood-vessels  (vaso- 
motor) and  skin  (pilomotor)  and  thirdly,  fibers  for  the  sweat  glands 
(secretomotor)  of  this  part.  The  former  pursue  a  straight  course 
from  the  spinal  cord  to  their  peripheral  effectors  (I),  while  the  latter 
are  first  diverted  into  the  sympathetic  ganglia  by  way  of  the  white 
rami  (II),  whence  they  are  again  directed  into  this  spinal  nerve  by 
way  of  the  gray  rami  (IV).  For  this  reason,  they  are  frequently  desig- 
nated as  recurrent  fibers.  It  seems  quite  probable  that  a  similar 
arrangement  exists  at  the  points  of  union  between  the  cranial  nerves 
and  the  sympathetic,  or  more  correctly  speaking,  the  parasjaupathetic 
system. 

The  peculiar  manner  of  distribution  of  these  fibers  is  well  illustrated 
by  that  of  the  pilomotors.^  Using  the  cat  as  an  example,  it  is  found 
that  the  latter  leave  the  spinal  gray  matter  by  way  of  the  anterior 
roots  of  the  fourth  thoracic  to  third  lumbar  nerve.  They  enter  the 
sympathetic  system  through  the  white  rami,  where  they  arborize  in  the 
ganglia  of  this  chain  to  form  connections  with  neighboring  ganglia 
above  and  below  their  point  of  entrance.  Each  ganglion  in  turn 
remits  a  certain  number  of  secondary  fibers  which  again  reach  the 
corresponding  spinal  nerve  by  way  of  the  neighboring  gray  ramus. 
From  here  they  are  distributed  to  the  smooth  muscle  cells  of  the  skin 
of  that  particular  region.  The  fact  that  the  sympathetic  ganglia 
permit  of  a  spreading  of  the  primary  impulse  may  be  proved  by  the 
stimulation  of  the  neighljoring  white  and  gray  rami.  For  example, 
while  the  excitation  of  a  certain  gray  ramus  will  yield  pilomotor  effects 
only  in  that  segment  of  the  body  to  which  the  corresponding  mixed 
nerve  is  distributed,  the  stimulation  of  the  neighboring  white  ramus 
most  generally  evokes  these  effects  in  the  areas  of  the  three  or  four 
adjoining  spinal  nerves.  Obviously,  this  result  can  onl}-  be  obtained 
if  the  primary  impulse  is  relaj'cd  to  neighboring  efferent  paths,  and 
naturally,  there  is  every  reason  to  believe  that  this  spreading  is  not 

1  While  the  production  of  "goose  flesh"  and  the  erection  of  the  hairs  are  usually 
classified  as  involuntary  phenomena,  cases  have  been  placed  on  record  which 
show  that  individuals  may  acquire  an  accurate  voluntary  control  over  these 
otherwise  purely  sympathetic  reactions. 


THE  SYMPATHETIC  AND  PARASYMPATHETIC  SYSTEMS  G35 

coiiriiiod  to  tlio  pilomotor  impulses,  but  also  involves  other  sympathetic 
impulses. 

Afferent  Conduction  in  the  Autonomic  System. — We  have  noted 
that  those  libers  of  the  anterior  horn  which  eventually  enter  the  white 
ramus  communicans,  terminate  around  the  cells  of  the  first  sympa- 
thetic ganglion  (Fig.  314,  S).  The  axons  of  the  latter  either  return 
to  the  spinal  nerve  by  way  of  the  gray  ramus  communicans  or  continue 
within  this  system  to  other  more  distant  ganglia.  The  neuron  form- 
ing the  connection  between  the  cord  and  the  sympathetic  ganglion 
constitutes  the  preganglionic  path  (P),  and  the  one  situated  on  the 
distal  side  of  the  ganglion,  the  postganglionic  path  (Po).  This  termin- 
ology, however,  is  not  always  indicative  of  real  conditions,  because 
some  of  the  preganglionic  fibers  may  pass  directly  through  the  first 
sympathetic  ganglia  without  entering  into  communication  by  synapse 
with  these  cells.  According  to  Langley,  the  precise  nature  of  a 
certain  sympathetic  fiber  may  be  ascertained  by  moistening  the 
ganglion  with  a  solution  of  nicotin  (N).     This  agent,  it  will  be  remem- 


7^ ^^ ^ &' 

^r^^--^ ^ 

Fig.  314. — Diagram  to  Illustrate  the  Action  of  Nicotin. 
C,  Spinal  cord;  P,  preganglionic  path;  S,  sympathetic  ganglion;  Po,  postganglionic 
path;  E,  effector;  I,  neuron  which  does  not  form  a  synapse  in  S;  II,  neuron  forming 
synapse  in  S;   N,  destroys  connections  in  synapse,  blocking  nerve  impulse  in  neuron 
//  but  not  in  /. 

bered,  first  stimulates  and  then  paralyzes  the  cells,  preeminently  at 
their  junction  with  the  axon  terminations  of  the  central  neurons. 
Consequently,  the  stimulation  of  the  preganglionic  path  must  remain 
without  effect  if  the  fibers  composing  the  latter  actually  enter  into 
synapses  within  the  nicotinized  area  (II).  The  reason  for  this  is 
that  the  nicotin  has  produced  a  block  within  the  ganglion.  Conversely, 
if  the  central  fibers  traverse  the  ganglion  without  entering  into  com- 
munication with  other  cells  (I),  they  must  necessarily  retain  their 
power  of  conducting  impulses  to  peripheral  parts,  because  the  nicotin 
does  not  affect  the  nerve-fibers.  In  the  latter  case,  therefore,  the 
excitation  of  the  preganglionic  path  must  give  rise  to  motor  effects. 
It  is  true,  however,  that  this  method  does  not  allow  of  a  universal 
application,  because  certain  animals,  such  as  the  dog,  are  very  re- 
sistant against  this  agent;  in  fact,  its  action  differs  even  in  the  same 
animal  when  applied  to  different  structures.  Thus,  it  has  been  found 
that  the  cervical  ganglia  are  much  more  susceptible  to  it  than  the 
ganglia  of  the  splanchnic  area. 

The  autonomic  nervous  system  is  essentially  a  distributing  mechan- 
ism and  hence,  its  ganglia  may  be  said  to  serve  primarily  the  purpose 


636  THE    AUTONOMIC    NERVOUS    SYSTEM 

of  relaj'  centers.  As  such  the}'  effect  a  considerable  increase  in 
the  number  of  the  efferent  channels,  because  when  the  preganglionic 
path  terminates  in  a  certain  sjonpathetic  ganglion,  its  fibers  arborize 
and  form  various  new  connections  with  these  cells.  The  postganglionic 
path,  therefore,  must  be  numerically  stronger  than  the  preganglionic. 
A  similar  multiplication  of  paths  results  in  the  next  ganglion  and  so  on 
until  the  periphery  has  been  reached,  where  we  find  such  intricate 
ramifications  of  fibers  as  the  plexuses  of  Meissner  and  Auerbach,  or  the 
plexus  cardiacus.  Obviously,  this  fan-like  expansion  of  the  primary 
path  into  multiple  secondary  and  tertiary  paths,  enables  the  principal 
center  to  control  a  large  number  of  effectors  and  a  wide  area  of  tissue. 
In  the  second  place,  it  renders  the  distal  ganglia  and  plexuses  partially 
independent  of  the  cerebrospinal  centers,  because  they  can  intercom- 
municate with  one  another  without  that  the  impulses  need  be  relayed 
within  the  cerebrospinal  system. 

The  formation  of  these  relatively  local  centers  for  the  control 
of  particular  processes,  necessitates  the  development  of  a  certain 
number  of  afferent  channels,  without  which  the  motor  actions  could  not 
attain  the  preciseness  required  of  them.  While  it  cannot  be  doubted 
that  these  afferent  elements  are  present,  it  must  be  admitted  that  they 
are  fewer  in  number  and  retain  for  the  most  part  a  local  importance. 
It  is  also  e%ddent  that  their  number  varies  considerably  in  different 
parts  of  the  autonomic  system.  This  must  necessarily  be  so  because 
certain  structures,  such  as  the  glands  along  the  intestinal  tract,  re- 
quire a  closer  functional  correlation  than  other  organs.  In  general, 
it  may  be  said  that  these  afferent  sj-mpathetic  neurons  serve  two 
purposes,  namely,  to  effect  perfectly  local  reflexes  and  to  consummate 
reactions  in  parts  remote  from  the  seat  of  the  stimulation.  In  the 
latter  case,  the  impulses  may  even  enter  consciousness  and  give  rise 
to  voluntary  actions.  This,  however,  is  rather  the  exception.  To 
illustrate,  the  stomach  or  intestine  may  be  excised  and  if  kept  under 
proper  conditions  of  moisture  and  temperature,  may  be  made  to  move 
and  to  secrete  in  a  manner  not  widely  different  from  normal.  This 
implies  that  these  organs  are  in  possession  of  local  nervous  mechanisms, 
consisting  of  afferent  and  efferent  arcs  and  their  corresponding  end- 
organs,  which  enable  them  to  continue  their  actions  even  when  iso- 
lated from  the  cerebrospinal  sj'stem  or  from  neighboring  sjmipathetic 
gangUa.  But  it  is  also  evident  that  these  organs  are  constantly  sub- 
jected to  stimuU  arising  elsewhere  in  the  autonomic  sj^stem  or  even 
in  the  cerebrospinal  system  itself.  Thus,  a  flow  of  gastric  juice  or  of 
any  other  digestive  secretion  may  be  evoked  by  stimuli  arising  else- 
where in  the  abdominal  cavit}'  or  in  the  receptors  of  the  mucous  mem- 
brane of  the  mouth,  the  taste-buds,  olfactory  cells,  and  others.  The 
fact  that  the  different  sjTnpathetic  paths  contain  afferent  fibers,  finds 
ample  proof  in  the  pressor  and  depressor  reactions  following  in  the  wake 
of  the  excitation  of  the  hepatic  and  mesenteric  plexuses.  "^  It  may  be 
1  Burton-Opitz,  Quart.  Jour,  of  Exp.  Physiol.,  iv,  1911,  93. 


THE  SYMPATHETIC  AND  PARASYMPATHETIC  SYSTEMS  637 

conchidccl  that  these  different  local  reflex  circuits  are  associated  by 
commissural  fibers. ' 

Lastly,  it  should  be  noted  that  the  afferent  impulses  of  the  auto- 
nomic system  may  pass  into  the  cerebrospinal  system  to  be  received 
eventually  in  consciousness  (Fig.  314,  V).  The  fact  that  a  path  of  this 
kind  exists,  may  be  gathered  from  the  work  of  Dogiel,^  who  has  found 
that  afferent  visceral  fibers  arise  in  certain  sensory  cells  of  the  sympa- 
thetic system  which  then  enter  the  posterior  root  and  arborize  around 
the  cells  of  the  spinal  ganglion.  From  here  these  visceral  impulses 
are  conveyed  inward  over  the  usual  afferent  tracts  of  the  spinal  cord. 
Thus  we  may  obtain  at  times  distinct  sensations  of  visceral  pressure, 
pain  and  temperature,  such  as  arise  in  the  course  of  the  movements 
of  the  stomach,  intestine,  bladder,  and  other  organs.  It  must  be 
admitted,  however,  that  the  viscera  are  relatively  insensitive  to  ordi- 
nary stimuli,  as  may  be  gathered  from  the  fact  that  the  handling  or 
cutting  of  internal  organs  does  not  give  rise  to  a  decided  sensation  of 
pain,  whereas  the  mere  opening  of  a  body-cavity  by  an  incision  through 
the  integument  can  scarcely  be  effected  without  local  or  general  anes- 
thesia. It  should  be  noted,  however,  that  the  sensation  of  visceral 
pain  need  not  be  restricted  to  the  area  in  which  it  has  been  produced, 
but  may  also  be  projected  to  the  surface  layers  of  the  body  by  way 
of  the  corresponding  cutaneous  somatic  fibers.  Thus,  a  diseased  organ 
may  give  rise  to  a  hypersensitiveness  (hyperalgesia)  and  tenderness 
to  mechanical  and  thermal  stimuli  in  an  area  of  the  integument  cor- 
responding to  the  distribution  of  these  fibers.  As  examples  of  referred 
visceral  pain  might  be  mentioned  the  radially  disseminated  pain  ex- 
perienced in  the  course  of  the  passage  of  calculi  through  the  biliary 
ducts  or  the  extreme  painful  sensations  which  may  be  elicited  by 
pressing  upon  the  integument  in  the  region  of  a  gastric  ulcer. 

In  general,  therefore,  it  may  be  said  that  the  autonomic  system 
possesses  the  same  functional  powers  as  the  cerebrospinal  system,  be- 
cause it  serves  as  a : 

(a)  Conductor  of  efferent  and  afferent  impulses, 

(6)  Center    for    reflex    action, 

(c)  Tonically  automatic  center  which  retains  the  parts  innervated  by  it  in  a 

condition  of  tonus,  and  as  a 
{d)  Center  for  the  regulation  of  the  trophic  condition  of  these  parts. 

Pseudo-  or  Axon-reflexes. — The  question  has  frequently  been 
asked  whether  reflexes  may  also  be  elicited  with  the  help  of  single 
ganglia  and  their  peripheral  connections?  This  should  remind  us 
first  of  all  of  the  controversy  pertaining  to  the  nature  of  the  patellar 
reflex  which  has  finally  been  decided  in  favor  of  the  view  that  it  is 
not  an  axon-reflex,  but  is  actually  effected  with  the  help  of  the  cor- 
responding spinal  center.  The  only  other  structure  which  need  be 
considered  in  this  connection  is  the  spinal  ganglion.     It  has  been  found 

1  Hoffman,  Jahresber.  fiir  die  ges.  Med.,  cclxxi,  1904,  113. 

2  Der  Bau  der  Spinalganglien  des  Menschen  und  der  Saugetiere,  Jena,  1908. 


638 


THE    AUTONOMIC    NERVOUS    SYSTEM 


that,  in  the  lower  forms,  its  cells  are  typically  bipolar,  while  in  the 
mammals  they  are  unipolar,  possessing  a  single  process  which  divides 
into  two  branches,  one  of  which  enters  the  spinal  cord  and  the  other, ' 
the  spinal  nerve.  As  commonly  conceived,  the  function  of  these 
fibers  is  to  conduct  impulses  from  the  periphery  to  the  posterior  region 
of  the  spinal  cord.  Naturally,  the  severance  of  the  corresponding  pos- 
terior root  would  render  these  fibers  useless  for  reflex  action,  because 
they  would  thereby  be  disconnected  from  their  efferent  channels 
and  motor-organs.  A  moment  ago,  however,  we  have  noted  that  the 
spinal  ganglia  receive  certain  afferent  fibers  from 
the  sympathetic  system.  Under  experimental  con- 
ditions these  afferent  sympathetic  fibers  may  also 
be  made  to  conduct  in  a  centrifugal  or  efferent 
direction.  It  need  not  surprise  us,  therefore,  to 
learn  that  the  stimulation  of  these  spinal  ganglia 
frequently  gives  rise  to  vasodilator  effects  in  that 
region  of  the  body  from  which  the  aforesaid  afferent 
fibers  have  been  derived.  It  is  highly  improbable 
that  an  effect  of  this  kind  is  produced  under  normal 
conditions,  although  it  may  arise  in  consequence  of 
inflammatory  reactions  in  the  region  of  the  spinal 
ganglia,  multiple  neuritis  and  other  conditions. 

While  our  search  for  axon-reflexes  within  the 
realm  of  the  cerebrospinal  system  has  thus  proved 
negative,  it  cannot  be  doubted  that  the  ganglia  of 
the  autonomic  system  are  well  adapted  for  this 
form  of  reflex  action,  because  practically  every  one 
of  them  is  a  reflex  center  dominating  the  function 
of  a  rather  circumscribed  region  of  the  body.  No 
definite  facts,  however,  are  at  hand  to  prove  that 
the  sympathetic  system  is  especially  constructed 
for  true  axon-reflexes.  The  example  usually  given 
is  the  following:  If  the  inferior  mesenteric  ganglion 
(Fig.  315)  is  isolated  from  the  central  nervous 
system  by  the  division  of  its  preganglionic  path 
(P),  but  is  left  in  functional  relation  with  the  blad- 
der (B)  through  the  two  hypogastric  nerves  (H),  the  stimulation 
of  the  central  end  of  one  of  these  nerves  invariably  evokes  a  con- 
traction of  the  musculature  of  the  opposite  half  of  this  organ.  If 
the  aforesaid  ganglion  is  now  moistened  with  a  solution  of  nicotin, 
this  motor  effect  cannot  be  obtained.  The  conclusion  to  be  de- 
rived from  this  experiment  is  that  this  "reflex"  cannot  be  effected 
without  the  help  of  the  cells  of  the  inferior  mesenteric  ganglion,  but 
since  the  normal  conditions  of  conduction  have  been  reversed  in  this 
case,  we  cannot  justly  regard  this  reaction  as  a  true  reflex.  For  this 
reason,  Langley  and  Anderson^  have  applied  to  it  the  term  of  pseudo- 

1  Jour,  of  Physiol.,  xvi,  1894,  410. 


Fig.  315.— Dia- 
gram Showing  Ner- 
vous Innervation 
OF  Bladder. 

C,  Spinal  cord ; 
JM,  inferior  mesen- 
teric ganglion;  P, 
preganglionic  path; 
Po,  post-ganglionic 
path  formed  by  H, 
the  hypogastric 
nerves;  B,    bladder. 


THE    SYMPATHETIC    AND    PARASYMPATHETIC    SYSTEMS       639 

or  axon-reflex.  Obviously,  the  stimulus  is  applied  here  to  normally 
efferent  fibers  from  wliich  the  impulse  is  then  transferred  at  the  central 
synapses  to  the  efferent  fibers  of  the  opposite  side.  This  transfer 
is  made  possible  by  the  fact  that  each  preganglionic  fiber  arriving 
in  this  ganglion,  divides  into  two  branches,  one  of  which  pursues  a 
direct  course  to  the  corresponding  side  of  the  bladder,  while  the  other 
makes  connections  by  synapse  with  the  fibers  forming  the  opposite 
hypogastric  nerve. 

On  closer  analysis,  however,  it  becomes  evident  that  this  particular 
experiment  docs  not  prove  anything  further  than  that  the  normal 
direction  of  conduction  in  the  hypogastric  fibers  may  be  reversed  by 
experimental  means.  This  is  not  a  new  fact,  because  Klihne  has  shown 
that  a  similar  reversion  may  be  effected  in  the  motor  nerves  of  skeletal 
muscle.  It  will  be  remembered  that  the  nerve  innervating  the  gra- 
cilis muscle  divides  into  two  branches,  one  of  which  supplies  the 
upper,  and  the  other,  the  lower  end  of  this  muscle  (Fig.  74).  'Inas- 
much as  a  contraction  may  be  evoked  in  its  upper  end  by  the  stimula- 
tion of  the  nerve  terminals  in  its  lower  end,  the  fibers  of  this  normally 
efferent  branch  must  be  able  to  conduct  the  impulses  so  generated  in 
an  afferent  direction.  It  should  not  be  assumed,  however,  that  this 
reversal  of  conduction  may  also  take  place  under  perfectly  normal 
conditions.  The  same  statement  applies  to  the  manner  of  conduction 
within  the  sympathetic  system,  because  we  have  not  been  able  to 
observe  these  phenomena  under  other  than  experimental  conditions. 
There  is  one  reaction,  however,  which  may  be  of  positive  value  and 
that  is  the  following:  If  an  irritant,  such  as  mustard  oil,  is  applied  to 
the  skin,  this  area  becomes  red,  swollen,  warm  and  painful  in  con- 
sequence of  the  dilatation  of  its  blood-vessels.  These  changes  may  also 
be  brought  about  after  the  sensory  fibers  from  this  region  have  been 
severed,  but  are  much  diminished  if  the  sensitiveness  in  this  part  is 
first  abolished  by  a  local  anesthetic.  It  appears,  therefore,  that 
this  vasomotor  reaction  is  not  effected  in  a  direct  manner,  but  reflexly. 
Now,  inasmuch  as  this  area  may  be  isolated  from  its  center  by  the 
division  of  its  afferent  fibers,  the  resultant  dilatation  of  the  blood- 
vessels must  have  been  brought  about  by  a  local  reflex  accomplished 
solely  with  the  help  of  peripheral  axons  and  their  collaterals.^ 

1  Bardy,  Skand.  Archiv  fur  Physiol.,  xxii,  1908,  194. 


SECTION  XVII 

THE    MEDULLA    OBLONGATA    AND    THE    CRANIAL 

NERVES 


CHAPTER  LII 


THE  FUNCTION  OF  THE  MEDULLA  OBLONGATA 

The  Medulla  as  a  Reflex  Center. — While  the  medulla  oblongata 
or  bulb  may  be  regarded  essentially  as  a  part  of  the  spinal  cord,  it 
really  possesses  a  much  greater  functional  importance  than  the  latter, 
because  it  gives  lodgment  to  a  number  of  centers  which  control  the 
most  vital  processes  in  our  body.     Thus,  a  separation  may  be  effected 


Vagoglossopharyngeal 

roots      Nucleus  of  the 
Restiform       I      fasdtulus  sqlitarius 


Vagus  nucleus 
Fasc'cu'us  sol'tarius 

Dc^cinding  root  of  vestibular 

nerve  (\'III) 
.,j-.^,^^ .  Vago-glossopharyngeal 

Ml 


Jr-  1  \tcrnal  arcuate  fibers 
— wr  Medial  lemniscus 
frSi^^^^  a\  Medial  acces.  olive 


Inferior  olive 


Fig. 


Pyramid 
External  arcuate  fibers 


316. — Cross-section  Through  the  Adult  Human  Medulla  Oblongata  at  the 
Level  of  the  IX  Cranl%.l  Nerve.      (From  Cunningham's  Anatomy.) 


between  this  structure  and  the  other  parts  of  the  central  nervous  sys- 
tem without  actually  destroying  the  life  of  the  animal,  but  its  isola- 
tion must  be  brought  about  by  sections  through  the  region  of  the 
pons  and  through  the  spinal  cord  below  the  nuclei  of  the  phrenic  nerves. 
If  the  latter  section  is  made  above  this  point,  the  ensuing  paralysis 
of  the  diaphragm  would,  of  course,  make  life  impossible.     Similarly, 

640 


THE    FUNCTION    OF   THE    MEDULLA    OBLONGATA  641 

the  destruction  of  the  medulla  itself  is  followed  l)y  an  almost  immediate 
cessation  of  the  respiratory  movements,  a  relaxation  of  the  vascular 
channels  and  a  stoppage  of  the  heart. 

The  centers  situated  in  the  domain  of  the  bulb  are  of  two  kinds, 
namely,  simple  reflex  and  dominating  or  automatic.  Regarding 
their  function,  nothing  further  need  be  said,  because  the  manner  in 
which  reflex  action  is  effected  has  already  been  discussed  in  detail 
in  an  earlier  chapter.  The  following  bulbar  reflex  centers  have  been 
localized  with  some  degree  of  accuracy: 

(a)  Closure  of  the  eyelids.  The  sensory  impulses  reach  the  medulla  from  the 
cornea,  conjunctiva,  and  vicinity  of  the  eyelids  by  way  of  the  trigeminus  nerve. 
The}-  are  transferred  to  the  motor  fibers  of  that  branch  of  the  facial  nerv6  which 
innervates  the  orbicularis  palpebrarum.  The  center  itself  extends  from  the  ala 
cinera  to  the  posterior  border  of  the  pons.  While  this  reflex  is  bilateral  in  character, 
the  volitional  closure  of  the  lids  may  be  unilateral  and  may  be  intensified  by  the 
contraction  of  the  neighboring  muscles  of  the  face. 

(6)  Center  for  sneezing.  The  afferent  arc  is  formed  by  the  trigeminus,  and  the 
efferent  arc  by  the  nerves  innervating  the  different  muscles  of  respiration.  In 
addition,  afferent  impulses  may  be  received  by  way  of  the  olfactory  and  optic 
nerves,  because  this  reflex  is  also  evoked  by  intense  odors  and  sudden  high  intensi- 
ties of  light. 

(c)  Center  for  coughing.  It  is  situated  above  the  center  for  respiration.  The 
sensory  side  of  this  reflex  circuit  is  formed  by  the  afferent  fibers  of  the  vagus,  and 
the  efferent  arc  by  the  nerves  innervating  the  muscles  of  the  larynx  and  the  expira- 
tory muscles  of  the  thorax. 

(d)  Center  for  mastication  and  sucking.  The  sensory  path  includes  the  second 
and  third  branches  of  the  trigeminus  and  the  glossopharyngeus.  The  motor 
path  includes  the  facialis  to  the  muscles  of  the  lips,  the  hypoglossus  to  the  tongue, 
and  the  third  branch  of  the  trigeminus  to  the  muscles  raising  and  lowering  the 
lower  jaw. 

(e)  Center  for  deglutition.  It  is  situated  near  the  floor  of  the  fourth  ventricle 
above  the  respiratory  center.  The  afferent  side  of  this  circuit  is  formed  by  the 
second  and  third  branches  of  the  trigeminus  and  the  vagus.  Its  efferent  side  is 
formed  by  the  vagus. 

(/)  Center  for  the  secretion  of  saliva.  It  is  placed  near  the  floor  of  the  fourth 
ventricle  and  may  be  activated  by  different  sensory  impulses.  Its  efferent  fibers 
enter  the  parasympathetic  system  and  appear  peripherally  as  the  chorda  tympani 
and  the  auriculotemporal  branch  of  the  inferior  maxillary  division  of  the  trigeminus. 

(g)  Center  for  vomiting.  Besides  the  afferent  fibers  of  the  vagus,  these  im- 
pulses may  also  be  derived  from  other  sensory  tracts,  such  as  the  optic  and  ol- 
factory.    The  chief  efferent  fibers  are  contained  in  the  vagus. 

The  Medulla  as  an  Automatic  Center. — The  foregoing  discussion 
shows  that  the  reflex  centers  of  the  medulla  are  practically  identical 
with  the  nuclei  of  the  different  cranial  nerves  concerned  in  these 
reactions.  For  this  reason,  the  latter  may  be  considered  as  gene- 
rating a  state  of  nervous  activity  very  similar  to  that  displayed  by 
the  spinal  nuclei  or  by  the  cells  of  the  automatic  centers  regulating 
the  most  vital  processes  in  our  body,  namely,  respiration,  the  action 
of  the  heart,  and  the  distribution  of  the  blood.  These  functions  are 
of  such  great  importance  that  the  medulla  is  capable  of  assuming 
through  them   a  position  almost  independent  of  the  cerebrum  and 

41 


642 


MEDULLA    OBLONGATA   AND    THE    CRANIAL   NERVES 


allied  structures.  Inasmuch  as  it  is  thus  placed  in  a  position  to  in- 
fluence the  respiratory,  cardiac  and  vasomotor  activities,  it  must  also 
dominate  in  an  indirect  way,  the  function  of  the  cerebral  centers. 

Lastly,  the  medulla  must  be  considered  as  an  organ  of  conduction, 
because  it  occupies  a  position  directly  in  the  path  of  the  cerebro- 
spinal tracts.  It  also  gives  origin  to  several  of  the  cranial  nerves  which 
in  this  way  are  enabled  to  gain  access  to  the  higher  centers.  All  in 
all,  therefore,  the  medulla  is  one  of  the  most  widely  connected  struc- 
tures of  the  nervous  system. 


Nuc.   dorsalis  vagi 

Nuc.  fasc.  solitarius 

Fasc.  solitarius 

Nuc.  fasciculus 

cuneatus 

Nuc.  XII 

Spinal  V  nuc 

Spinal  V  tr. 

Nuc.  sal.  inf. 

X  root 

Nuc.  ambiguus 


Reticular 
formation 


Inferior  olive 


XII  root 
Fig.  317. — Diagraiwmatic  Cboss 
AT  THE  Level  of  the  Vagus  Nerve, 
(Herrick.) 


Ala  cinerea 
Trigonum  hypoglosei 
Nuc.  vestibularis  spinalis 

Fasc.  long.  med. 

Lemniscus  V 

Corpus  restiforme 


Tr.  spino-cereb. 
dorsalis 


Tr.  rubrospinalis 

Tr.  spino-cereb. 
'        ventralis 
•Lemniscus  spinalis 

Tr.  tectospinalis 
Lemniscus  medialis 
Pyramidal  tract 
i-.sECTiON  Through  the  Human  Medulla  Obloxgata 
Illustrating  Details  of  Functional  Localization. 


CHAPTER  LIII 


THE  CRANIAL  NERVES 

The  Functional  System  of  the  Cranial  Nerves. — We  have  seen 
above  that  the  spinal  nerves  enter  the  cord  by  a  series  of  roots 
arranged  in  strict  agreement  with  segmentalispi.  The  sensory  fibers 
and  corresponding  gray  matter  occupy  the  dorsal  realm  of  this  struc- 
ture, while  the  motor  fibers  with  their  gray  matter  are  situated  ante- 
riorly. The  cranial  nerves  show  a  similar  functional  arrangement, 
because  the  sensory  centers  are  situated  dorsally  to  the  motor,  but  the 
segmentalism  observed  in  the  case  of  the  spinal  fibers  has  here  given 
way  to  a  perfectly  definite  grouping  of  the  different  units.  This  enables 
all  impulses  of  Uke  character  to  become  closely  associated.  In  general, 
therefore,  it  may  be  said  that  the  twelve  pairs  of  cranial  nerves  repre- 
sent twelve  pairs  of  interlocking  systems,  regulating  one  or  several 
independent  functions,  irrespective  of  their  anatomical  location.  This 
fact  shows  that  the  grouping  of  the  components  of  the  cranial  nerves 


THE    CRANIAL   NERVES 


643 


is  based  upon  function  rather  than  upon  structure,  and  implies  that 
these  componc^nts  are  arranged  in  accordance  with  their  terminations. 
Thus,    the   chissification  of  these  nerves  should  be  based  upon  the 


Out  edge  of  cerehetiar  peduncle 


Pineal  body 

Colhculus  mfmori   ' 
Puhtinar  of  Ihalnr, 
Uesial  geniculate  body 

Lateral  geniculate  body 

4th  nerve 
5th  nerve 


■piQ  318. — View  from  Dorsal  Aspect  of  Upper  Part  of  the  Spinal  Cord,  Medulla 
Oblongata,  Pons,  Fourth  Ventricle,  Mid-brain,  Thalamus,  etc..  Dissected  in  situ. 
(./.  Symington.) 

type  of  organ  with  which  they  are  united  peripherally  or  upon  the 

type  of  center  in  which  they  arise  or  terminate.^     Thus,  it  happens 

that  a  certain  cranial  nerve  may  embrace  fibers  from  two  different 

1  Herrick,  Wood's  Reference  Handbook  of  the  Med.  Sciences,  iii,  1914,  321. 


644 


MEDULLA  OBLONGATA  AND  THE  CRANIAL  NERVES 


sense-organs  which  then  diverge  centrally  to  seek  the  respective  centers 
for  these  functions.  Again,  a  certain  sense-organ  may  distribute  its 
ingoing  fibers  to  two  different  cranial  nerves,  after  which  they  reunite  to 
attain  a  common  center. 

This  structural  divergency  implies  that  the  cranial  nerves  may  be 
efferent  or  afferent  in  their  function,  as  well  as  mixed.  The 
efferent  fibers  arise,  of  course,  in  cells  situated  within  the  domain  of 
the  cerebrum,  isthmus  and  medulla,  while  the  cells  of  the  afferent 
fibers  are  situated  in  special  ganglia  at  some  distance  from  these  parts. 
In  the  latter  case,  the  same  arrangement  is  found  to  exist  as  in 
the  spinal  ganglia,  i.e.,  the  sensory  cell  sends  out  an  axon  which  soon 
divides  into  two  branches,  one  of  them  tending  toward  the  brain,  and 
the  other  toward  the  peripheral  sense-organ.  The  trophic  centers 
of  the  motor  fibers,  therefore,  are  situated  within  the  brain,  and  those  of 
the  sensory  fibers  in  the  peripheral  ganglia. 

With  the  exception  of  the  first  and  second  pairs,  the  cranial  nerves 
arise  from  the  medulla  oblongata  and  neighboring  parts,  their  nuclei 
being  situated  chiefly  in  the  gray  matter  below  the  floor  of  the  fourth 
ventricle  and  its  prolongation  below  the  aqueduct. 

1.  The  olfactory  nerve,  or  nerve  of  smell,  forms  the  connection  be- 
tween the  olfactory  region  of  the  nose  and  the  olfactory  center.     These 

Olfactory  tract 


Granule  cell 
Mitral  cell 
Glomerulus 
Olfactory  nerve 
Ethmoid  bone 
Olfactory  epithelium 

Fig.  318a. — Diagram  of  the  Connections  of  the  Olfactory  Bulb.     (Herrick.) 


fibers  arise  in  the  olfactory  cells  of  the  aforesaid  area,  whence  they 
attain  the  primary  center  within  the  olfactory  bulb  by  passing  through 
the  cribriform  plate  of  the  ethmoid  bone.  The  arborizations  formed  by 
these  fibers  in  this  particular  locality,  are  known  as  glomeruli  and  repre- 
sent synapses  between  the  primary  and  secondary  olfactory  neurons. 
The  latter,  which  begin  here,  are  known  as  the  mitral  cells.  Their 
axons  continue  inward  and  form  the  so-called  olfactory  tract,  ending 
finally  in  the  secondary  olfactory  nucleus,^  at  the  base  of  the  olfac- 
tory bulb.  The  olfactory  center  is  then  attained  by  three  paths  which 
are   known   as   the  medial,  intermediate  and  lateral  olfactory  stria?. 

1  Zwaardemaker,  Ergebn.  d.  Physiol.,  i,  1902;  also:  Edinger,  Vergl.  Anat.  des 
Gehirns,  Leipzig,  1908. 


THE    CRANIAL   NERVES  645 

The  center  itself  contains  the  following  sul)di visions:  (a)  The  lateral 
olfactory  nucleus  which  extends  backward  into  the  tip  of  the  temporal 
lobe  of  the  cerebrum  as  far  as  the  point  of  contact  between  the  ventro- 
lateral extremities  of  the  hippocampus  and  hippocampal  gyrus, 
(h)  the  medial  olfactory  nucleus  into  which  the  medial  olfactory  striae 
are  discharged,  and  (c)  the  intermediate  olfactory  nucleus  in  the  anterior 
perforated  substance  in  which  the  intermediate  olfactory  stria?  termin- 
ate. These  nuclei  are  intimately  connected  with  other  cerebral  centers 
and  diverse  motor  paths,  thereby  enabling  the  sensory  impressions 
of  smell  to  become  associated  with  other  sensations  as  well  as  with 
the  different  motor  mechanisms.  This  close  correlation  permits  these 
nuclei  to  play  the  part  of  reflex  centers,  in  which  the  olfactory  impulses 
are  transferred  to  efferent  paths  and  to  the  motor  end-organs.  In 
man,  these  olfactory  reflex  centers  are  dominated  by  a  psychic  or 
cortical  center  which,  as  will  be  shown  later,  occupies  the  hippocampal 
convolution,  especially  its  distal  end,  the  uncus.  Different  association 
paths  connect  this  area  with  other  cortical  centers. 

2.  The  optic  nerve,  or  nerve  of  sight,  conveys  the  impulses  from 
the  retina  to  the  thalamus,  where  they  are  transferred  onward  to  the 
center  for  vision  in  the  occipital  region  of  the  cerebral  cortex.  The 
essential  receptive  element  of  the  eye  is  the  retina  which  forms  the 
innermost  coat  of  this  sense-organ  and  contains  neurons  of  the  fol- 
lowing four  types:  (a)  The  rods  and  cones,  (b)  the  bipolar  cells,  (c) 
the  ganglion  cells,  and  (d)  the  horizontally  arranged  association  neu- 
rons. The  fibers  of  the  optic  nerve  take  their  origin  from  the  ganglion 
cells,  but  this  does  not  mean  that  these  elements  constitute  neurons 
of  the  first  order.  In  fact,  as  the  real  receptors  of  the  retina  are  the 
rods  and  cones,  these  elements  should  be  regarded  as  forming  the 
neurons  of  the  first  order  of  the  optic  path.  Their  impulses  are 
transmitted  across  the  external  molecular  layer  to  neurons  of  the  sec- 
ond order,  the  cell  bodies  of  which  are  situated  in  the  internal  granular 
layer.  These  data  tend  to  show  that  the  ganglion  cells  of  the  retina 
are  already  neurons  of  the  third  order  which  then  leave  the  eye  through 
the  optic  papilla  to  form  the  optic  nerve  proper. 

Having  reached  the  optic  chiasma  at  the  ventral  aspect  of  the 
cerebrum,  these  fibers  enter  into  a  decussation  which  carries  them  either 
in  part  or  as  a  whole  to  the  opposite  side  of  the  brain,  A  complete 
crossing  is  effected  in  fishes,  amphibians,  reptiles  and  most  birds,  and  a 
partial  one  in  man  and  the  mammals,  namely,  in  those  animals  in 
which  the  visual  fields  overlap  and  which  possess  stereoscopic  vision. 
There  is,  however,  no  evidence  at  hand  to  show  that  the  crossing  in 
the  latter  is  absolutely  symmetrical,  because  the  number  of  fibers 
remaining  on  the  same  side  seems  to  become  the  greater,  the  higher 
the  rank  of  the  animal  in  the  scale  of  the  Animal  Kingdom.  In  man, 
however,  the  fovea  centralis  or  yellow  spot  seems  to  be  innervated 
bilaterally,  i.e.,  the  fibers  emerging  from  this  area  pass  to  both  visual 
centers.      This  crossing  carries  the  fibers  from  the  inner  halves  of  the 


646 


MEDULLA    OBLONGATA    AND    THE    CRANIAL    NERVES 


retinae  to  the  opposite  side  and  leaves  the  fibers  from  their  outer 
halves  on  the  same  side.  Thus,  the  right  occipital  center  innervates 
the  right  halves  of  both  retinae,  and  the  left  center  their  left  halves. 
The  yellow  spot  of  each  eye,  on  the  other  hand,  is  innervated  by  both 
centers.  ^ 

Posteriorly  to  the  chiasma,  these  crossed  and  uncrossed  fibers  con- 
tinue upward  and  backward  in  the  form  of  the  optic  tracts.  Having 
passed  the  surface  of  the  thalamus,  they  divide  into  two  groups,  one 
of  which  terminates  in  the  lateral  geniculate  body  and  the  other  in 
the  roof  of  the  colliculus  of  the  midbrain.  In  this  way,  certain  reflex 
centers  are  established  which  are  concerned  with  the  movements  of  the 


LEFT  RETINA 


RIGHT  RETINA. 


^C/>f 


"^crpiT^^ 


Fig.  319. — Diagram  Showing  the  Probable  Relations  Between  the  Parts  of  the 
Retina  and  the  Visual  Area  of  the  Cortex.  The  Bilateral  Representation  of  the 
Fovea  is  Indicated  by  the  Course  of  the  Dotted  Lines.     (Schafer.) 

eyeballs,  the  process  of  accommodation,  and  other  reactions.  This  is 
true  especially  of  the  colliculus,  while  the  thalamus  seems  to  be  set 
aside  rather  as  a  relay  station  in  the  path  leading  to  the  visual  center 
situated  in  the  occipital  cortex  of  the  cerebrum.  The  latter,  therefore, 
forms  a  direct  dependency  of  the  cortical  center  and  hence,  its  impor- 
tance must  increase  with  the  development  of  the  center  for  vision.  We 
find  here,  therefore,  an  arrangement  very  similar  to  that  previously 
noted  in  the  case  of  the  olfactory  mechanism,  i.e.,  the  hght  impressions 
received  by  the  retinae,  may  actually  reach  the  center  for  vision  to  be 
associated  or  may  be  transferred  unto  a  motor  path  in  the  lower  reflex 
center  situated  in  the  superior  colliculus.  In  the  former  case,  they  must 
first  give  rise  to  a  psychic  impression,  and,  in  the  latter,  to  a  simple 
1  Wilbrand    and    Sanger,    Die    Neurologie    des    Auges,    Wiesbaden,    1904. 


THE    CRANIAL   NERVES 


647 


reflex  reaction.  This  lower  center  is  intimately  connected  with  the 
path  for  tactile  and  auditory  sensations  by  way  of  the  neighboring 
cerebral  peduncle  and  is  closely  associated  with  the  nuclei  of  the  third 
and  fourth  cranial  nerves.  Connection  is  also  made  here  with  the 
other  cranial  and  spinal  nerves  by  way  of  the  fasciculus  longitudinalis 
medial  is. 

3.  Th(>    oculomotor   nerve    arises   from    the    oculomotor   nucleus 
situated  in  llie  ccntial  gray  matter  near  the  floor  of  the  aqueduct  of 


toe^ 


Fig.  320. — Diagram  of  the  Pbincipal  Components  of  the  Optic  Apparatus. 

(Cunninohain.) 

Sylvius.  The  latter  is  composed  of  three  groups  of  cells,  namely, 
(a)  a  lateral  colony  of  large  ganglion  cells  situated  next  to  the  median 
line  below  the  aqueduct,  (6)  a  smaller  median  colony  consisting  of  large 
cells,  and  (c)  a  median  colony  composed  of  much  smaller  cells.  This 
nerve  is  motor  in  its  function  and  embraces  fibers  for: 

(a)  The  internal  rectus,  superior  rectus,  inferior  rectus  and  inferior  oblique 
muscles  of  the  eye.  According  to  Bernsheimer/  these  fibers  arise  in  the  group  of 
cells  constituting  the  lateral  subnucleus.  The  coordination  of  these  muscles  with 
those  of  the  opposite  eyeball,  is  not  under  the  guidance  of  the  will.  This  nerve 
also  innervates  the  muse,  levator  palpebra-  superioris.  ^ 

1  Handbuch  der  Augenheilkunde,  Leipzig,  1900. 


648 


MEDULLA    OBLONGATA    AND    THE    CRANIAL    NERVES 


(6)  The  sphincter  muscle  of  the  iris.  These  fibers  take  their  origin  in  the 
median  colony  of  small  cells  and  terminate  in  the  ciliarj*  ganglion.  Here  they  make 
connection  with  postganglionic  fibers  formed  by  sj'mpathetic  neurons  (nervi 
ciliares  breves). 

(r)  The  ciliarj-  muscle.  These  fibers  arise  in  the  median  colony  of  large  cells 
and  end  in  the  ciliary  ganglion.  Their  postganglionic  continuations  are  formed  by 
sj-mpathetic  neurons  (nervi  ciliares  breves). 

We  shall  see  later  that  the  contraction  of  the  ciliar}"  muscle  allows 
the  lens  of  the  eye  to  become  more  convex,  a  condition  necessary  for 
near  vision.  This  change  is  usually  accompanied  by  a  constriction 
of  the  pupil.  These  two  reactions  occur  simultaneously  and  constitute 
accommodation  reflexes.  In  addition,  the  pupil  is  also  constricted 
whenever  a  high  intensity  of  light  is  permitted  to  strike  the  eye.     This 


if,f4l 


Edinger-Westphal   nucleus. 
Principal  nucleus. 
^Median  nucleus. 


Nucleus  of  4th  nerve. 


Fig.  321. — Nuclei    of    Origin    of     the    Third     and    Fourth    Nerves. —  (From 

Poirier  and  Charpy.) 

reflex  constitutes  the  so-called  light  reflex.  In  accordance  with  the 
preceding  discussion,  it  must  now  be  evident  that  the  afferent  arc  of  the 
circuit  for  the  light  reflex  is  formed  b}^  the  optic  tract,  and  the  efferent 
arc  by  the  oculomotor  nerve.  Its  center  lies  in  the  reflex  area  of  the 
optic  tract,  i.e.,  in  the  colliculus  and  corpora  quadrigemina  near  the 
aqueduct  of  Sylvius.  The  constriction  of  the  pupil  associated  with 
near  vision  and  constituting  the  so-called  accommodation  reflex,  finds  its 
origin  in  certain  sensory  stimuli  which  are  set  up  in  the  eye  muscles 
whenever  the  eyes  are  converged  for  a  near  point.  The  afferent  arc 
of  this  reflex  circuit,  therefore,  does  not  encroach  upon  the  optic  tract 
and  is  not  directly  concerned  with  vision. 


THE    CRANIAL    NERVES 


649 


4.  The  trochlear  nerve  arises  in  the  trochlear  nucleus  which  is 
situated  in  the  central  gray  matter  below  the  floor  of  the  aqueduct  just 
posteriorly  to  the  lateral  subnucleus  of  the  oculomotor  nerve.  These 
fibers  pass  horizontally  backward  and  emerge  behind  the  posterior 
corpora  quadrigemina,  where  they  cross  in  the  anterior  medullary 
velum.  It  is  a  motor  nerve  supplying  fibers  to  the  superior  oblique 
muscle  of  the  eyeball.  The  action  which  this  muscle  gives  rise  to, 
simultaneously  with  the  muscle  attached  to  the  opposite  eyeball,  is  not 
under  the  control  of  the  will. 

5.  The  trigeminus  nerve  originates  from  two  roots,  a  small  anterior 
or  portio  minor,  and  a  large  posterior  or  portio  major.  The  former  is 
motor  and  the  latter  sensory  in  its  function.  Its  motor  root  arises 
in  part  from  a  small  nucleus  in  the  pons  and  partly  from  ganglion 


N.  opht 


Principal 

motor 

nucleus 


Descending 
spinal  root 


N.  max.  sup.  N.  max.  inf. 

Fig.  322. — Nuclei  of  Origin  of  the  Fifth  Cranial  Nerve. 

after  Van  Gehtichten.) 


{From  Poirier  and  Charpy, 


cells  situated  in  the  region  of  the  corpora,  laterally  to  the  aqueduct 
of  Sylvius.  Its  musculomotor  fibers  are  distributed  peripherally 
through  the  ramus  masticatorius  to  the  different  muscles  of  mastica- 
tion, as  well  as  to  the  muscles  of  deglutition,  inclusive  of  the  muse, 
mylohyoid eus,  the  tensor  veli  palatini  and  muse,  azygos  uvulae.  It  also 
contains  secretomotor  fibers  for  the  lacrimal  gland  and  sweat-glands, 
and  vasomotor  fibers  for  the  tongue  and  face.  The  latter,  of  course, 
are  of  sympathetic  origin  and  use  the  path  of  this  nerve  merely  as  a 
highway  to  reach  distal  parts. 

This  nerve  is  of  importance  chiefly  on  account  of  its  sensory  power, 
because  it  conveys  the  sensations  of  touch,  pain  and  temperature  from 
the  skin  of  the  face,  the  adjoining  region  of  the  SK^alp,  the  mucous 
membrane  lining  the  nasal  and  oral  cavities,  and  from  the  teeth  and 


650  MEDULLA    OBLONGATA    AND    THE    CRANIAL    NERVES 

eyes.  Stimuli  brought  to  bear  upon  its  distant  receptors,  give  rise 
to  a  large  array  of  reflex  actions,  such  as  inhibition  of  the  respiratory 
movements,  closure  of  the  glottis,  slowing  of  the  heart-beat,  and  secre- 
tion of  the  tears  and  saliva.  The  trigeminus  is  also  said  to  convey  the 
sensations  of  taste  from  the  anterior  third  of  the  tongue,  but  it  is  more 
than  probable  that  the  taste  fibers  contained  in  this  nerve,  have  been 
derived  from  the  glossopharyngeus  or  nervus  intermedins.  The 
sensory  fibers  of  this  nerve  arise  in  the  Gasserian  ganglion  in  a  manner 
similar  to  the  fibers  of  the  spinal  ganglion.  Their  peripheral  branches 
pass  to  the  sense-organs,  while  their  central  branches  divide  and  are 
arranged  as  two  roots  which  end  (a)  in  the  sensory  nucleus  situated 
laterally  to  the  motor  nucleus  and  (6)  in  a  long  nucleus  which  extends 
through  the  entire  dorsal  portion  of  the  medulla.  This  arrangement 
enables  the  impulses  to  be  relayed  from  the  sensory  nucleus  of  this 
nerve  through  the  median  raphe  to  the  cortex  of  the  cerebrum.  In 
addition,  collaterals  are  sent  to  all  the  nuclei  of  the  cranial  nerves 
arising  in  the  medulla,  with  the  exception  of  the  nucleus  abducens. 
It  should  also  be  mentioned  that  this  nerve  communicates  with  the 
ganglion  sphenopalatinum  and  ganglion  submaxillare  which  form  the 
outposts  of  the  sympathetic  system  of  this  region. 

6.  The  abducens  nerve  originates  in  a  nucleus  situated  below 
the  colliculus  facialis,  and  emerges  from  the  posterior  edge  of  the  pons. 
It  is  a  motor  nerve  and  innervates  the  external  rectus  muscle  of  the 
eyeball.  Like  the  third  and  fourth  cranial  nerves,  it  is  under  the  con- 
trol of  the  will,  but  not  when  made  to  act  synchronously  with  others  to 
produce  those  movements  of  the  eyeballs  which  are  necessary  in 
binocular  vision  and  accommodation. 

7.  The  facial  nerve  arises  from  a  conspicuous  nucleus  in  the  teg- 
mental region  of  the  pons  and  leaves  the  brain  at  the  inferior  margin 
of  this  structure,  somewhat  lateral  to  the  point  of  emergence  of  the 
sixth  nerve.  It  is  chiefly  a  motor  nei-ve  and  supplies  the  muscles  of 
the  face,  those  of  a  part  of  the  scalp,  and  those  of  the  ear,  inclusive  of 
its  intrinsic  muscles.  As  such  it  governs  the  expression  of  the  face. 
This  may  be  gathered  from  the  fact  that  its  division  is  soon  followed 
by  a  distortion  and  a  drawing  over  of  the  paralyzed  side  of  the  face 
toward  the  normal.  This  deviation  which  eventually  may  also  in- 
volve some  of  the  bones,  is  produced  by  the  tonic  pull  exerted  by  the 
muscles  of  the  normal  side.  In  many  cases,  however,  the  paralyzed 
muscles  finally  show  a  condition  of  contracture  which  then  tends  to 
antagonize  this  pull  so  that  the  face  again  assumes  a  more  normal 
appearance.  Another  muscle  which  takes  part  in  this  paralysis  is  the 
orbicularis.  The  inability  to  close  the  space  between  the  eyelids 
exposes  the  cornea  to  mechanical  and  thermal  influences  which  in 
turn  give  rise  to  a  copious  secretion  of  lacrimal  fluid,  and  possibly 
also  to  inflammatory  processes.  The  paralysis  of  Horner's  muscle 
prevents  the  offlow  of  the  tears  into  the  nasal  cavity.  In  view  of  the 
fact  that  the  facial  nerve  also  innervates  the  muscles  which  have  to  do 


THE    CRANIAL   NERVES 


651 


with  nasal  respiration,  its  division  leads  to  a  loss  of  movement  of  the 
nostrils.     Phonation  is  impaired. 

This  nerve  also  contains  secretomotor  and  vasomotor  fibers  for 
the  submaxillary  and  sublingual  glands  which  reach  their  destination 
by  way  of  the  chorda  tympani.  It  also  embraces  secretomotor  fibers 
for  the  lacrimal  glands  which  pass  through  the  ganglion  sphenopala- 
tinum  and  reach  the  second  branch  of  the  trigeminus  and  subsequently 
the  nervus  zygomaticus  and  nervus  lacrimalis.  Its  sensory  fibers 
convey  taste  impressions  from  the  front  part  of  the  tongue.  They 
form  the  nervus  intermedins  and  are  affixed  to  the  chorda  tympani 
and  lingual  nerves. 


fV/A 


Fig.  323. — The  Origin  of  the  Sixth  and  of  the  Motor  Part  of  the  Seventh  Nerve. 
YI.,  Sixth  nerve;  VII.,  seventh  nerve;  a.VII.,  ascending  part  of  the  root  of  seventh 
shown  cut  across  near  the  floor  of  the  fourth  ventricle;  ;;,  genu  of  seventh  nerve-root; 
71.VI.,  chief  nucleus  of  the  sixth  nerve;  n.'VI.,  accessory  nucleus  of  sixth;  n.VII.,  nucleus 
of  seventh;  d.V.,  descending  root  of  fifth;  pyr.,  pyramid-bundles;  VIII.v.,  vestibular 
root  of  eighth  nerve.      (Schdfer.) 


8.  The  auditory  nerve  consists  of  two  groups  of  fibers  possessing  a 
certain  anatomical  and  functional  independency.  One  of  them  is  con- 
cerned with  hearing  and  forms  its  cochlear  branch,  and  the  other  with 
the  sense  of  equilibrium  and  forms  its  vestibular  branch.  In  the  horse 
and  sheep  these  fibers  are  in  fact  absolutely  separated  from  one  another 
throughout  their  course. 

The  auditory  nerve  enters  the  bulb  in  two  parts,  an  external  and 
an  internal.  The  fibers  of  the  former  are  derived  chiefly  from  the 
cochlea,  and  those  of  the  latter  from  the  semicircular  canals  and  the 
vestibule  of  the  internal  ear.  The  first  connect  with  the  spiral  gan- 
glion of  the  cochlea  and  the  latter  with  the  vestibular  ganglion  of  the 
semicircular  canals.  These  peripheral  stations  are  comparable  to 
the  spinal  ganglia,  because  the  cells  composing  them  send  out  processes 
which  soon  divide  into  two  branches.     One  of  these  connects  with  the 


652 


MEDULLA  OBLONGATA  AND  THE  CRANIAL  NERVES 


peripheral  receptor,  and  the  other  with  the  central  nucleus.  If  we 
now  follow  these  fibers  in  the  latter  direction,  we  will  find  that  they 
pursue  a  separate  course;  those  contained  in  the  vestibular  branch 
ending  in  the  nuclei  of  Deiters  and  Bechterew  in  the  cerebellum,  and 
those  belonging  to  the  cochlear  division  in  the  ventral  and  dorsal 
nuclei  of  the  pons.  From  these  primary  relaj^  stations  the  auditory 
impulses  are  conveyed  onward  to  the  auditory  center  in  the  superior 
gyrus  of  the  temporal  lobe  of  the  cerebrum,  but  the  course  pursued 
by  them,  has  not  been  full}'  made  out  as  j'et.  It  seems,  however, 
that  the  largest  number  of  the  fibers  arising  in  the  ventral  or  accessory 
nucleus  acusticus,  cross  to  the  opposite  side  of  the  cerebrum.     They 


TO  VERMIS 


TO   HEMISPHERE 


FIBRES    O 

VESTIBULA 
ROOT 


NERVE 


pJ.b 


(GANGLION   OF 


ENDINGS    '"-(V    SCARPA 
iN  MACULAE 
&AMPULUE 


Fig.  324. — The  Cotthse  axd  Coxxectioxs  of  the  Fibeks  Formixg  the  VESTtBrLAB 
Root  of  the  Auditor y  Ner\'e. 
r.,  Restiform  body;  T",  descending  root  of  fifth  nerve;  p.,  principal  nucleus  of  ves- 
tibular root:  d,  fibers  of  descending  vestibular  root;  n.d.,  a  cell  of  the  descending  ves- 
tibular nucleus;  D,  nucleus  of  Deiters;  B,  nucleus  of  Bechterew;  n.t.,  nucleus  tecti 
(fastigii)  of  the  cerebellum;  ■plh.,  posterior  (dorsal)  longitudinal  bundle.     {Schiifer.) 

select,  however,  somewhat  different  routes.  Some  of  them  tend 
directlj^  across  through  the  corpus  trapezoideum,  while  others  reach 
this  structure  by  passing  around  the  restiform  body  and  through  the 
tegmental  region.  From  here  thej'  attain  the  superior  olivary  body 
of  the  same  and  opposite  sides  and  subsequently^  the  lateral  fillet  or 
lemniscus.  Having  traversed  the  coUiculus  or  median  geniculate 
body,  thej'  terminate  eventuallj'  in  the  psychic  area  for  audition, 
situated  in  the  superior  gyrus  of  the  temporal  lobe. 

The  dorsal  nucleus  or  tuberculum  acusticum  is  connected  with 
this  center  by  secondary'  sensory  neurons  which  form  the  medullary 
or  auditory  striae,  a  band  of  fibers  traceable  along  the  floor  of  the 
fourth  ventricle.     At  the  median  raphe  these  fibers  turn  and  a  large 


THE    CRANIAL   NERVES 


653 


number  of  them  cross  the  micUine  to  attain  the  lateral  lemniscus  of 
the  opposite  side,  whence  they  reach  the  gray  matter  of  either  the 
inferior  colliculus  or  median  geniculate  body.  These  structures  are 
connected  with  the  psychic  area  for  hearing  by  way  of  the  auditory 
radiation  which  passes  through  the  inferior  extremity  of  the  internal 
capsule. 

We  obsei-ve,  therefore,  that  the  auditory  nerve  finally  gives  rise  to 
a  decussation  which  bears  a  close  resemblance  to  that  effected  by  the 
optic  nerve,  but  the  degree  of  crossing  has  not  been  determined  as 
yet  with  certainty.  As  we  shall  see  later,  this  fact  is  very  important, 
because  it  helps  to  explain  some  of  the  symptoms  resulting  from  uni- 
lateral destruction  of  the  center  of  hearing.     In  the  second  place,  it 


tub.ac 


riBRES  TO  NUCL.LEMNISCI 
&CORPORA  QUADRIGEMINA 


NERVE-ENDINGS 

IN  ORGAN  OF  CORTI 

Fig.  325. — The  Course  and  Conxections  of  the  Fibres  Forming  the  Cochlear  Root 

OF  THE  Auditory  Nerve. 
r.,    Restiform    body;    V,    descending   root   of   the   fifth    nerve;   tub.ac,    tuberculum 
acusticum;  n.acc,  accessory  nucleus;  s.o.,  superior  olive;  n.tr.,  nucleus  of  trapezium; 
n.VI,  nucleus  of  sixth  nerve;  VI,  issuing  root-fiber  of  sixth  nerve.     {Schafer.) 

will  be  seen  that  the  median  geniculate  body  may  serve  the  purpose  of 
a  secondary  auditory  center  and  hence,  assume  a  position  similar  to 
that  of  the  lateral  geniculate  body  which  is  really  a  subordinate  center 
for  vision.  Thirdly,  sufficient  experimental  evidence  is  at  hand  to 
show  that  the  auditory  centers  form  the  starting  points  of  certain  motor 
paths  which  are  used  in  the  reflex  actions  resulting  in  consequence 
of  auditory  stimuli. 

9.  The  glossophar3nigeus  nerve  is  motor  and  sensory  in  its  function. 
It  emerges  from  the  side  of  the  meduUa,  its  motor  fibers  originating 
from  two  nuclei,  known  as  che  nucleus  ambiguus  which  forms  the 
ventral  area  of  the  vagus  nucleus,  and  the  nucleus  dorsaUs  which  is 
situated  below  the  floor  of  the  fourth  ventricle.  Its  sensory  fibers  are 
derived  from  the  ganglion  superiore  and  ganglion  petrosum.  The 
peripheral  branches  of  these  pass  to  the  receptors  and  their  central 


654 


MEDULLA    OBLONGATA    AND    THE    CRANIAL    NERVES 


branches  in  part  to  the  nucleus  alse  cinereae  and  in  part  to  the  nucleus 
tractus  solitarii.  Its  sensory  and  motor  fibers  are  thereby  brought 
into  close  relationship  with  those  of  the  vagus  nerve. 

Its  musculomotor  function  is  restricted  to  the  muscles  of  the 
pharynx  (muse,  stylopharyngeus)  and  its  secretomotor  function  to 
the  parotid  gland.  The  latter  is  reached  by  way  of  the  ganglion 
petrosum,  nervus  tympanicus,  nervus  petrosus  superficialis  minor, 
ganglion  oticum  and  nervus  auriculotemporalis.  Its  sensory  fibers 
are  in  relation  with  the  mucous  membrane  of  the  tongue,  pharynx. 


Fig.  326. — Diagram  Showing  the  Brain  Connections  of  the  Vagus,  Glossopharyngeal, 
Auditory,  Facial,  Abducens,  and  Trigeminal  Nerves.     {After  Obersteiner.) 


tonsils,  tympanic  cavity  and  Eustachian  tube.  It  also  conveys 
the  sensations  of  taste  from  the  posterior  third  of  the  tongue  and  the 
lateral  aspect  of  the  fauces. 

10.  The  vagus  or  pneumogastric  nerve  arises  from  the  same  nuclei 
as  the  ninth  nerve,  and  emerges  from  the  side  of  the  medulla  posterior 
to  the  superficial  origin  of  the  preceding.  It  is  a  mixed  nerve.  Its 
motor  fibers  are  traceable  to  the  nucleus  ambiguus  and  the  dorsal 
or  vagus  nucleus.  Its  sensory  fibers  take  their  origin  in  the  ganghon 
jugulare  and  ganglion  nodosum  and  pass  to  the  nucleus  alse  cinereae 
and,  in  small  numbers,  also  to  the  nucleus  tractus  solitarii.  While 
the  function  of  this  nerve  will  be  considered  in  detail  in  connection  with 


THE    CRANIAL   NERVES 


655 


the  organs  innervated  by  it,  it  may  be  stated  at  this  time  that  it  is 
primarily  concerned  with  respiration,  the  action  of  the  heart,  and  the 
musculomotor  and  secretomotor  processes  of  the  digestive  organs. 

(a)  Respiration.  It  supplies  motor  fibers  to  the  muscles  of  the  larynx,  trachea 
and  bronchi.  The  most  important  nerves  to  be  mentioned  in  this  connection  are 
its  superior  and  inferior  laryngeal  branches.  It  also  serves  as  the  sensory  nerve 
of  the  larynx  (sup.  laryngeus)  and  the  lungs.  The  latter  are  directly  concerned 
with  the  self-regulation  of  respiration. 

(6)  The  Heart.  The  vagus  conveys  inhibitor  impulses  to  this  organ,  and  also 
sensory  impulses  from  this  region  by  way  of  its  "depressor  fibers." 


Fig. 


Xll. 
[HYPOGLOSSAL] 


327. — Cross-sectiox  of  Medull.^  Showing  Nuclei  of  Ner\-es  x  and  xii. 
{Cunningha7n.) 


(c)  Digestive  Organs.  The  vagus  innervates  the  sphincters  of  the  pharynx 
and  the  musculature  of  the  esophagus,  stomach  and  intestine.  It  sends  secreto- 
motor fibers  to  the  stomach,  intestine,  pancreas  and  possibly  also  to  other  abdom- 
inal organs.  The  vasomotor  mechanisms  of  these  organs  are  supplied  with  fibers 
from  the  solar  plexus.  While  the  latter  in  turn  communicates  with  the  thoracic 
sympathetic  system  through  the  splanchnic  nerves,  it  is  also  intimately  connected 
with  the  vagus  system. 


11.  The  accessory  nerve  is  formed  from  several  upper  roots  which 
take  their  origin  in  the  medulla,  and  from  a  series  of  lower  roots  which 
arise  from  the  anterior  gray  matter  of  the  spinal  cord  as  low  as  the 
fifth  to  seventh  cervical  vertebras.  It  is  a  motor  nerve  and  supphes 
the  sternocleidomastoid  and  trapezius  muscles. 


656  MEDULLA    OBLONGATA    AND    THE    CRANIAL    NER\^S 

12.  The  hypoglossal  nerve  emerges  from  the  furrow  between  the 
anterior  pyramid  and  ohvary  body  of  the  medulla.  Its  deep  origin 
is  formed  by  a  nucleus  situated  in  the  floor  of  the  fourth  ventricle. 
A  commissure  unites  the  nuclei  in  the  two  halves,  and  each  nucleus 
receives  fibers  from  the  opposite  cerebral  hemisphere.  It  is  a  motor 
nerve  and  innervates  the  muscles  of  the  tongue,  inclusive  of  the  muse, 
geniohyoideus  and  th}reohyoideus. 


SECTION  XVIh 
THE  CEREBRUM 


CHAPTER  LIV 
THE  GENERAL  FUNCTION  OF  THE  CEREBRUM 

General  Arrangement  of  the  Gray  Matter. — The  investigation  of 
the  function  of  the  brain  of  which  the  cerebral  hemispheres  form  the 
largest  part,  is  usually  carried  on  along  structural,  experimental 
physiological,  and  clinical  lines.  A  complete  functional  picture, 
however,  can  only  be  obtained  if  the  data  derived  from  these  sources, 
are  compiled  and  compared  with  one  another.  On  the  histological 
side,  it  is  of  interest  to  note  that  the  chief  neurons  of  the  cerebral 
cortex  are  pyramidal  in  shape  and  are  directed  in  such  a  way  that  their 
apices  are  turned  toward  the  surface  and  their  bases  toward  the  white 
matter.  The  three  poles  of  these  cells  are  usually  occupied  by  den- 
drites, the  principal  one  of  which  arises  from  the  apex.  The  axon 
is  derived  from  a  hillock  in  the  middle  of  the  base  of  the  cell-body 
and  pursues  a  rather  straight  course  into  the  white  matter,  giving 
off  collaterals  in  its  course. 

While  this  cell  is  typical  of  the  cerebral  cortex,  it  does  not  exhibit 
the  same  size  and  form  in  all  parts  of  this  organ.  Throughout  the 
cortex,  however,  it  is  united  with  others  to  form  four  or  five  separate 
layers  which  border  immediately  upon  the  central  core  of  white  matter. 

(a)  The  most  superficial  layer  lies,  of  course,  in  contact  with  the  enveloping 
membranes  of  the  cerebrum,  i.e.,  with  the  pia  mater,  and  is  known  as  the  plexiform 
or  molecular  layer.  Its  thickness  amounts  to  0.25  mm.  Besides  the  neuroglia 
cells,  it  contains  chiefly  dendrites  from  the  deeper  layers  and  a  few  small  cells,  the 
processes  of  which  are  directed  parallel  to  the  surface  of  the  cortex.  These  proc- 
esses terminate  within  this  layer  and  do  not  penetrate  the  white  matter.  It 
is  believed,  therefore,  that  their  function  is  chiefly  associative  for  the  cells  of  the 
cortex. 

(6)  The  layer  of  pyramidal  cells  Ij'ing  directly  underneath  the  former,  is  char- 
acterized by  the  presence  of  a  large  number  of  cells  possessing  a  pyramidal  shape. 
CampbelU  arranges  them  in  three  laj-ers,  this  classification  being  based  upon 
differences  in  their  size.  The  inner  ones  are  larger  than  the  outer.  As  has  been 
mentioned  above,  their  apices  are  directed  outward  and  send  their  dendrites  into 
the  molecular  layer.  The  axon  arises  from  the  basal  margin  of  the  cell  and  enters 
the  white  matter  underneath.     The  dendrites  of  the  pyramidal  cells  are  rough  and 

^  Hist.  Studies  on  the  Local,  of  Cort.  Function,  Cambridge,  1905. 
42  657 


658 


THE    CEREBRUM 


thorny;  in  fact,  it  has  been  claimed  that  these  projections  form  actual  sj^naptic 
connections  with  neij^hboring  neurons. 

(f)  The  stellate  or  granular  layer  contains  numerous  cells  possessing  a  stellate 
shape  and  short  irregular  axons.     It  is  also  known  as  the  middle  cell  lamina. 

(d)  The  inner  fiber  lamina  contains  numer- 
ous large  and  medium-sized  cells  which  are 
known  as  the  cells  of  Betz.  The  latter  are  not 
present  in  all  parts  of  the  cerebral  cortex,  but 
are  most  conspicuous  in  its  motor  area  next  to 
the  fissure  of  Rolando.  Their  axons  pass  into 
the  white  matter. 

(e)  The  layer  of  fusiform  or  polymorphous 
cells  is  situated  next  to  the  white  matter.  It 
is  also  known  as  the  inner  cell  lamina  and  is  com- 
posed of  different  types  of  cells  of  which  the 
spindle-shaped  ones  are  the  most  prominent. 
It  also  embraces  a  number  of  pyramidal  cells 
similar  to  those  found  in  the  outer  realm  of  the 
more  superficial  layer,  but  their  tips  are  directed 
inward  and  their  bases  toward  the  surface. 
These  are  the  cells  of  Martinotti.  In  addition, 
this  layer  contains  a  cell  resembling  the  second 
type  of  Golgi  with  branching  axons.  The  latter 
terminate  in  the  neighboring  gray  matter. 

General  Arrangement  of  the  White 
Matter. — The  medullary  portion  of  the 
cerebrum  begins  directly  below  the  poly- 
morphous layer.  When  stained  in  ac- 
cordance with  Weigert's  method  which 
brings  out  the  medullated  nerve  fibers, 
the  white  matter  is  seen  to  be  arranged 
in  radial  striae,  i.e.,  its  fibers  expand  fan- 
hke  from  a  common  center  formed  by 
the  internal  capsule.  Some  of  these  ra- 
dial streamers  may  be  followed  to  the 
surface  of  the  cortex  and  may  be  seen  to 
give  rise  here  and  there  to  networks  of 
fibers  which  are  placed  transversely  to 
the  course  of  the  former,  A  layer  of 
this  kind  is  found  directly  underneath 
the  surface  of  the  cortex,  but  it  does  not 
extend  throughout  the  brain.  It  is 
most  conspicuous  in  the  hippocampal 
region.  Another  layer  is  situated  be- 
tween the  molecular  and  pyramidal 
zones,  and  still  another  internally  to  the 
granular  zone.  These  layers  are  known 
respectively  as  the  outer  and  inner 
stripes  of  Baillarger.  A  special  layer 
of  transverse  fibers  is  found  in  the  visual 
area  of  the  occipital  lobe  where  it  bisects  the  granular  layer.     This  is 


Fig,  328. — Postcentral  Convolu- 
tion, GoLGi  Method. 
1,  Plexiform  layer;  2,  small 
pyramids;  3,  medium  pyramids; 
4,  superficial  large  pyramids;  5, 
granules;  6,  deep  large  pyramids; 
7,  deep  medium  pyramids.    (Cajal.) 


THE  GENERAL  FUNCTION  OP  THE  CEREBRUM       659 

the  line  of  Gennari,  which  really  corresponds  to  the  outer  stripe  of 
Baillarger. 

It  will  be  seen,  therefore,  that  the  cortex  of  the  cerebrum  presents 
a  definite  histological  structure  which,  however,  does  not  remain  the 
same  in  its  different  regions.  Certain  minor  differences  appear  here 
and  there,  which  enable  us  to  tell  from  which  particular  area  a  certain 
section  has  been  taken.  In  making  this  distinction,  we  should  be 
guided  by  (a)  the  thickness  of  the  entire  cortex,  (6)  the  relative  thick- 
ness of  its  different  zones,  (c)  the  type  of  cells  found  in  each  layer, 
and  (d)  the  character  of  the  radial  and  transverse  striie  of  fibers.  Thus, 
it  is  to  be  noted  that  the  thickness  of  the  human  cortex  varies  from  about 
4  mm.  in    its  motor  region  to  about  2  mm.  in  other  parts.     In  the 


/ 

Fig.  329. — Necroglia  Cells  of  Cortex  Cerebri.     Golgi  Method.     (G.  Retzitis.) 

former  area  are  found  the  large  pyramidal  cells  of  Betz  which  are  char- 
acteristic motor  elements.  In  addition  it  is  to  be  observed  that  the 
layer  of  pyramidal  cells  is  very  thick,  while  the  granular  layer  is  thin. 

The  visual  area  of  the  occipital  lobe  is  characterized  by  a  very 
prominent  granular  layer  w^hich,  as  has  been  stated  above,  is  really 
divided  into  two  by  a  broad  band  of  transverse  fibers.  The  distinguish- 
ing feature  of  the  association  areas  of  the  frontal,  parietal  and  oc- 
ciptal  lobes  is  the  highly  developed  outer  layer  of  pyramidal  cells. 

Classification  of  the  Tracts  of  the  Cerebrum. — The  fibers  of  the 
cerebral  white  matter  are  arranged  in  three  distinct  groups,  namely: 

(a)  Those  which  connect  the  hemispheres  with  the  outlying 
structures  of  the  nervous  system,  i.e.,  with  the  thalamus,  pons,  medulla 
and  spinal  cord. 

^  Brodmann,  Vergl.  Localisationslehre  der  Grosshimrinde,  Leipzig,  1909;  also 
Ramon  y  Cajal,  Stud,  liber  die  Hirnr.  des  Menschen,  Leipzig,  1906,  or  Lewan- 
dowsky,  Handb.  der  Neurologie,  Jena,  1910. 


660 


THE    CEREBRUM 


(&)  Those  which  unite  different  parts  of  the  same  hemisphere 
with  one  another,  and 

(c)  Those  which  extend  from  one  hemisphere  to  the  other.  The 
first  group  forms  the  so-called  projection  system,  the  second,  the 
association  system  and  the  third,  the  commissural  system.  Naturally, 
each  area  of  the  cortex  must  be  equipped  with  two  sets  of  fibers,  one 
of  which  conducts  away  from  it  and  the  other  toward  it.  In  the  case 
of  the  projection  system,  the  terms  of  afferent  and  efferent  may  be  used 


!FiG.  330. — Schema  of  the  Projection  Fibers  of  the  Cerebrum  and  of  the  Peduncles 
OF  the  Cerebellum;  Lateral  View  of  the  Internal  Capsule. 
A,  Tract  from  the  frontal  gyri  to  the  pons  nuclei,  and  so  to  the  cerebellum  (frontal 
cerebro-cortico-pontal  tract) ;  B,  the  motor  (pyramidal)  tract;  C,  the  sensory  (lemniscus) 
tract;  D,  the  visual  tract;  E,  the  auditory  tract;  F,  the  fibers  of  the  superior  peduncle 
of  the  cerebellum;  G,  fibers  of  the  middle  peduncle  uniting  with  A  in  the  pons;  H, 
fibers  of  the  inferior  peduncle  of  the  cerebellum;  J,  fibers  between  the  auditory  nucleus 
and  the  inferior  colliculus;  K,  motor  (pyramidal)  decussation  in  the  bulb;  Vt,  fourth 
ventricle.     The  numerals  refer  to  the  cranial  nerves.     {After  Starr.) 

to  distinguish  these  fibers  from  one  another,  but  this  terminology 
is  not  applicable  to  the  association  and  commissural  systems,  because 
these  fibers  establish  communication  between  different  central  parts  and 
do  not  possess  a  true  motor  or  sensory  function.  The  projection  system 
is  made  up  of  the  following  afferent  and  efferent  tracts: 

A.  Afferent,  (a)  Thalamocortical. — These  fibers  arise  in  the  gray  matter  of  all 
parts  of  the  optic  thalamus  and  radiate  outward  to  every  area  of  the  cerebral  cor- 
tex. In  accordance  with  their  distribution,  they  are  grouped  in  the  form  of  a 
frontal,  parietal,  occipital  and  ventral  stalk.  Those  forming  the  first  group,  do  not 
invariably  pass  directly  to  the  frontal  lobes,  but  may  end  in  the  caudate  and 
lenticular  nuclei.     Those  destined  for  the  occipital  lobes,  form  the  so-called  optic 


THE    GENERAL    P^UNCTION    OF    THE    CEREBRUM  661 

radiation.  They  enuTfic  from  the  ouUt  [)!irt  of  (he  pulvinar  and  cxtornal  Kcnicvi- 
late  body. 

(6)  The  Fillet  Syste/n  of  Fibers. — This  is  tlic  tract  which  enables  the  impulses 
from  the  different  sensory  paths  of  the  cerebrospinal  system  to  reach  the  thalamus 
and  subthalamic  region. 

(c)  The  S II  Iter i or  Cerebellar  Peduncle. — This  tract  connects  the  central  ganglia 
of  the  cerebellum  with  the  thalamus  and  subthalamic  region.  Some  of  them  may 
pass  directly  through  and  aroimd  this  structure  to  reach  the  region  of  the  fissure 
of  Rolando. 

('/)  The  Aiiditory  Radiation. — These  fibers  extend  from  the  internal  geniculate 
body  to  the  temporal  lobe.  They  traverse  the  posterior  extremity  of  the  internal 
capsule  under  the  lenticular  nucleus. 

B.  Efferent,  (a)  The  Pyramidal  Tract. — These  fibers  arise  in  the  motor  area 
of  the  cortex  and  pass  through  the  corona  radiata  into  the  internal  capsule.  Here 
they  are  grouped  in  the  genu  and  anterior  two-thirds  of  the  posterior  limb.  In 
their  downward  course  they  enter  the  crusta  and  pyramids  of  the  pons  and  medulla. 
Most  of  them  cross  the  midline  in  the  upper  part  of  the  spinal  cord  to  enter  the 
crossed  pyramidal  tract.  The  others  continue  onward  on  the  same  side  w^here  they 
form  the  direct  pyramidal  tract,  but  cross  over  gradually  in  the  lower  part  of  the 
cord. 

(6)  The  frontopontine  fibers  take  their  origin  in  the  cortex  of  the  frontal  lobes 
and  eventually  gain  the  mesial  extent  of  the  crusta  of  the  crus  cerebri.  They 
terminate  in  the  formatio  reticularis  of  the  pons  or  nucleus  pontis. 

(c)  The  temporopontine  fibers  originate  from  the  two  upper  temporal  convolu- 
tions and  enter  the  outer  extent  of  the  crusta.  From  here  thej^  enter  the  pons, 
where  they  terminate  in  the  nucleus  pontis  and  are  brought  into  relation  with  the 
middle  peduncles  of  the  cerebellum.  This  path,  therefore,  serves  as  the  chief 
efferent  bridge  between  the  cerebrum  and  cerebellum,  the  afferent  connection 
between  these  organs  being  represented  by  the  fibers  passing  between  the  cere- 
bellar cortex  and  dentate  nucleus  to  the  superior  cerebellar  peduncle,  red  nucleus, 
optic  thalamus  and  the  cerebral  cortex  of  the  opposite  side. 

The  association  system  unites  the  different  areas  of  the  cerebral 
cortex  of  the  same  side  with  one  another.  ■  Some  of  these  fibers  merely 
dip  downward  into  the  white  matter  to  clear  the  bottom  of  the  sulci 
and  to  enter  the  cortex  immediately  adjoining,  while  others  pass  to 
more  remote  regions.  For  this  reason,  these  fibers  are  said  to  form 
short  and  long  association  paths,  the  most  prominent  of  which  are  the : 

(a)  Uncinate  fasciculus  which  connects  the  orbital  convolutions  of  the  frontal 
lobe  with  the  anterior  segment  of  the  temporal  lobe. 

(b)  Cingulum  which  passes  between  the  anterior  perforated  space  and  the 
hippocampal  gyrus  and  temporal  lobe. 

(c)  Longitudinal  superior  fasciculus  which  forms  the  connection  between  the 
frontal,  perietal  and  occipital  cortex. 

(d)  Longitudinal  inferior  fasciculus  which  extends  along  the  occipital  and 
temporal  lobes. 

(e)  Occipitofrontal  fascicidus  which  is  situated  internally  to  the  corona  radiata 
and  next  to  the  caudate  nucleus. 

The  commissural  system  consists  of  three  chief  bridges  which  unite 
the  two  hemispheres,  namely : 

(a)  The  corpus  callosum  consists  of  fibers  which  arise  in  all  parts  of  the  cortex 
with  the  exception  of  the  anterior  and  posterior  segments  of  the  temporal  lobes  and 
the  olfactory  bulb.  They  originate  in  cells  of  the  cortex  but  may  also  be  the 
collaterals  of  certain  projection  axons.  Having  reached  the  other  side,  they  arborize 
extensively. 


662 


THE    CEREBRUM 


(6)  The  anterior  commissure  connects  the  olfactory  and  certain  portions  of  the 
temporal  lobes.  It  pursues  a  course  through  the  anterior  wall  of  the  third  ventricle 
anterior  to  the  pillars  of  the  fornix. 


Fig.  331. — Lateral  View  of  a  Human  Hemisphere,  Showing  the  Bundles  of  Asso- 
ciation Fibers. 
A,  A,  Between  adjacent  gyri;  B,  between  frontal  and  occipital  areas;  C,  between 
frontal  and  temporal  areas,  cingulum;  D,  between  frontal  and  temporal  areas,  fasciculus 
uncinatus;  E,  between  occipital  and  temporal  areas,  fasciculus  longitudinalis  inferior; 
C.N,  caudate  nucleus;  O.T,  thalamus.     {After  Starr.) 


Fig.  332. — Dlageam  of  Association,  Commissural,  and  Projection  Fibers  of  Brain. 
A,  Corpus  callosum;  B,  anterior  commissure;  C,  basal  ganglia;  D,  endings  of  com- 
missural fibers;  E,  sensory  cortex;  M,  motor  cortex;  F,  endings  of  association  fibers  from 
motor  cortex  (collaterals  of  projection-fibers) ;  G,  ending  of  association-fibers  from 
sensory  center;  H,  projection-fibers  from  motor  cortex  passing  to  spinal  centers;  /, 
projection-fibers  from  sensory  cortex;  a,  b,  c,  collaterals.     (Adapted  from  Cajal.) 

(c)  The  hippocampal  commissure  is  formed  in  the  hippocampus  of  one  side  and 
ends  almost  wholly  in  the  same  structure  of  the  opposite  side.  It  is  closely  con- 
cerned with  the  sense  of  smell. 

Mode  of  Development  of  the  Cerebrum. — In  early  embryonic 
life  the  nervous  system  first  presents  itself  as  a  dorsal  tube,  known  as 


THE  GENERAL  FUNCTION  OF  THE  CEREBRUM 


G03 


the  neural  lube.  It  is  fonued  by  an  invagiiKition  of  the  cpiblast.' 
Its  cavity  possesses  a  somewhat  larger  caliber  in  front  than  in  the 
region  of  the  spinal  cord,  and  becomes  subdivided  into  three  vesicles 
by  two  constrictions.  These  are  designated  respectively  as  the  fore- 
brain,  midbrain  and  hindbiain.  To  begin  with,  the  walls  of  this  tube 
are  thin,  being  composed  solely  of  epithelial  cells.  The  nervous 
elements  develop  a  little  later  and  show  a  differentiation  into  neuro- 
blasts and  spongioblasts,  the  former  eventually  giving  rise  to  nerve- 
cells  and  the  latter  to  the  supporting  tissue  or  neuroglia.  In  several 
places,  how(>V{M-,  the  original  epithelium  remains  undifferentiated  and 


.Anferior  neunport 

iPalhan  cffelencephalon 


Ditnctphahn 


^Corpus  striatum 


/Interior  neuropore 


Mesencephalon 
Isthmus 


Future  pcnVme  — r 
flcKure 


Rhombencephalon 


OpI'C  recess 

Future  pontine 


flexure 


Mesencephalon 

Cephalic 
■    flexure 


PhombemephaJon 


Fig.  333. — An  Enlarged  Model  of  the  Brain  of  a  Human  Embryo  3.2  Mm.  Long 
(About  Two  Weeks  Old).  The  Outer  Surface  is  Shown  at  the  Left,  and  on  the 
Right  the  Inner  Surface  After  Division  of  the  Model  in  the  Median  Plane.  The 
Anterior  Neuropore  Marks  a  Point  Where  the  Neural  Tu-be  is  Still  Open  to  the 
Surface  op  the  Body.  The  Pallium  is  the  Region  from  Which  the  Cerebral  Cortex 
Will  Develop.  The  Optic  recess  Marks  the  Portion  of  the  Lateral  Wall  of  the 
Diencephalon  from  Which  the  Hollow  Optic  vesicle  Has  Evaginated.  (After  His,  from 
Prentiss'  Emhryologjj.) 

finally  gives  rise  to  a  layer  of  similar  cells,  known  as  the  ependyma. 
This  relationship  is  shown  best  in  the  hindbrain,  where  the  posterior 
wall  of  the  neural  canal  fails  to  develop  nervous  elements  and  reaches 
maturity  merely  as  a  layer  of  epithehal  cells  covering  an  expanse  of 
the  tube.  This  is  the  fourth  ventricle.  In  other  places,  again,  the 
nervous  elements  grow  very  rapidly  and  lead  to  the  formation  of  more 
or  less  circumscribed  structures.  The  cerebellum,  for  example,  is 
developed  by  an  offshoot  from  the  dorsal  wall  of  the  tube,  while  the 
pons  and  medulla  are  formed  by  a  more  even  outgrowth  round  the  entire 
central  canal.  The  details  of  the  development  of  the  brain  lie,  of 
course,  outside  the  scope  of  this  book  and  must  be  obtained  from 
works  of  more  specialized  character. 

1  Keibel  and   Mall,   Manual  of  Human  Embryology,  Philadelphia,   1912. 


664 


THE    CEREBRUM 


Comparative  Physiology  of  the  Cerebrum. — In  the  course  of  verte- 
brate evolution,  the  prunitive  reflex  stem  of  the  nervous  system  event- 
ually acquires  a  number  of  structures  which  collectively  make  up  the 
brain.  Its  constituent  elements  are  the  hindbrain  (rhombencephalon), 
midbrain  (mesencephalon),  tweenbrain  (diencephalon)  and  forebrain 
(prosencephalon).  The  one  named  last  is  formed  by  the  cerebral 
hemispheres.  Obviously,  these  complex  masses  find  their  origin  in 
the  adjuncts  to  the  head  ganglia  of  the  lowest  forms  which,  as  has 
previously  been  pointed  out,  are  primarily  concerned  with  the  forma- 
tion of  the  sense  of  smell,  sight,  touch,  etc.  The  point  to  be  empha- 
sized is  that  these  areas  are  developed  from  small  beginnings  and  that 


Fig.  334.  —  Diagram- 
matic Representation  of 
THE  Head  of  a  Turtle,  to 
Show  the  Position  op  the 
Cerebrum  C  and  Optic 
Lobes  O. 


Fig.  335. — Diagrammatic  Representation  of  the 
Br.\in  of  a  Frog  {A)  and  Shark  {B). 
ON,  Olfactory  nerves;  OL,  olfactory  lobe;  C,  cere- 
brum; T,  tween  brain;  OpL,  optic  lobes;  Ce,  cerebellum; 
M,  medulla;  Co,  spinal  cord;  OC,  olfactory  capsules; 
OB,  olfactory  bulb.  The  cranial  nerves  are  indicated 
by  Roman  numerals. 


their  mass  and  complexity  is  in  accord  with  the  position  of  the  animal 
in  the  scale  of  the  Animal  Kingdom, 

Thus,  we  find  that  the  olfactory  realm  occupies  almost  the  entire 
cerebrum  of  the  fishes,  and  forms  the  most  conspicuous  part  of  the  brain 
of  the  reptilia  and  amphibia.  This  condition  permits  of  only  one  con- 
clusion, namely,  that  the  sense  of  smell  is  especially  well  developed  in 
these  animals,  and  that  their  existence  is  mainly  dependent  upon  ol- 
faction. Moreover,  while  their  reactions  are  almost  wholly  reflex, 
they  must  also  possess  a  moderate  power  of  associating  these  sensa- 
tions. As  we  ascend  the  scale  of  the  Animal  Kingdom,  this  sense 
becomes  retrogressive.  A  constantly  increasing  number  of  other 
mechanisms  are  added  to  the  hemispheres  which  enable  the  animal 


THE  GENERAL  FUNCTION  OF  THE  CEREBRUM 


665 


to  assume  a  more  diversified  position  in  nature.  This  is  true  partic- 
ularly of  birds,  their  more  elaborate  powers  being  directly  attributable 
to  a  greater  development  of  the  corpus  striatum  and  cerebellum.  In 
mammals,  on  the  other  hand,  these  Ixxlies  remain  relatively  small, 
whereas  the  external  shell  of  the  cerebrum,  or  pallium,  is  brought  into 
much  greater  prominence.  These  differences  have  led  to  the  division 
of  the  contituents  of  the  cerebrum  into  two  groups,  namely,  those 
which  are  intinuxtely  associated  with  the  sense  of  smell,  and  those 
which  are  chiefly  concerned  with  vision,  hearing  and  touch.     The 


Cingtilate 


Body  of  corpus  callosum 
Intermediate  mass 
Fornix 
Septum  pellucidum 

Marginal  gyrus        1^^ 
Gcnuof  corpus  callosum      ^^^^^tMtBS^ 


Tela  choroidea  ventriculi  tertii 
Cingulate  gyrus 
Callosal  fissure 

Spleniwm  of  corpus  callosum 
Paracentral  lobule 
Central  fissure 


Subparietal  fissure 
Precuneate  lobule 

Parieto-occip.  fissure 
Calcarine  fissure 


Cuneate  lobuU 


Lamina  terminalis 

Optic  recess 

Optic  nerve 

Optic  commissure 

Hypophysis 


Corpus  mamillare 
3rd  ventricle 
Cerebral  peduncle 
Pons 
Suprapineal  recess 
Pineal  body 
Cerebral  aqueduct 


Cerebellurn 
HeduUa  oblongata 
'  ith  ventticU 
/Superior  medullary  velum 
Corpora  quadrigemina 


Fig.  336. — Median  Section  of  an  Adult  Brain.     (/.  Symington.) 


former  are  spoken  of  collectively  as  the  archipallium,  and  the  latter  as 
the  neopallium.  The  first  system  is  the  more  primitive.  Its  impor- 
tance gradually  diminishes  in  favor  of  the  second. 

As  a  natural  consequence  of  this  evolution  we  find  that  the  cerebral 
hemispheres  increase  in  volume  and  complexity  until,  in  the  mammals, 
they  become  larger  than  the  whole  of  the  rest  of  the  brain  put  together. 
They  overshadow  the  primitive  olfactory  apparatus  completely,  and 
extend  backward  across  the  brain-stem  as  far  as  the  middle  of  the 
cerebellum.  In  this  way,  it  comes  to  pass  that  the  primitive  reflex 
cerebrum  of  the  lower  forms  which  is  largely  apportioned  to  smell, 


666  THE    CEREBRUM 

is  finally  changed  into  the  complex  association  organ  of  the  higher 
animals.  As  such  it  is  destined  eventually  to  dominate  all  processes 
of  life,  because  it  gives  rise  to  the  psychic  products  involved  in  con- 
sciousness, perception,  volition,  thought  and  memory.  In  the  higher 
forms,  therefore,  all  reactions  are  referable  in  last  analysis  to  the 
psychic  processes,  because  while  they  may  not  always  be  the  direct 
outcome  of  cerebral  activity,  the  latter  unfailingly  determines  the 
condition  of  the  body  as  a  whole  and  hence,  also  the  power  of  reaction 
of  its  constituent  tissues  and  organs. 

The  brain  of  the  higher  animals,  therefore,  possesses  a  distinguish- 
ing feature  in  its  many  areas  of  nervous  tissue  which  are  primarily 
intended  to  be  adjuncts  to  the  different  motor  and  sensory  mechanisms. 
This  statement,  however,  should  not  imply  that  they  are  all  psychic  in 
their  function ;  in  fact,  they  are  not  so  to  begin  with.  These  additions, 
as  has  been  stated,  bring  about  an  increase  in  the  mass  and  weight  of 
the  brain.  Thus,  we  find  that  the  human  brain  weighs  about  1400 
grams  in  the  male  and  1240  grams  in  the  female,  and  is  heavier  than 
that  of  any  of  the  lower  forms,  excepting  the  whale  and  elephant. 
Even  a  casual  study  of  the  behavior  of  these  three  types  of  animals 
will  show  that  man  is  distinctly  superior  to  the  other  two,  and  even 
to  those  animals  which,  relatively  speaking,  possess  the  same  amount 
of  brain  tissue. 

The  reason  for  this  is  not  difficult  to  detect.  It  lies  in  the  fact  that 
a  large  part  of  the  human  brain  is  taken  up  by  nervous  material  which 
gives  rise  to  those  associations  which  are  necessary  for  reflection, 
intelligence,  and  volition.  In  other  words,  the  human  brain  possesses 
the  distinguishing  feature  of  being  more  of  a  psychic  mechanism  than 
that  of  any  other  animal.  It  will  be  seen,  therefore,  that  while  the 
absolute  amount  of  brain  tissue  of  such  animals  as  the  dog,  ape  and 
man  remains  practically  the  same  in  all  three,  the  human  brain  has 
lost  much  of  that  kind  of  nervous  material  which  is  ordinarily  set 
aside  for  motor  action  and  sensation.  Instead,  it  has  acquired  certain 
units  for  the  formation  of  those  associations  which  add  a  distinct 
psychic  quality  to  these  fundamental  processes.  This  gradual  evolu- 
tion of  the  cerebral  hemispheres,  therefore,  accomplishes  a  shifting 
of  function  from  lower  centers  to  a  higher  psychic  realm  situated  in  the 
cortex.  In  the  human  brain,  this  transfer  of  function  is  portrayed 
best  by  the  relationship  existing  between  the  cortical  or  psychic 
centers  for  vision  and  hearing  and  the  corresponding  lower  ''reflex" 
centers  situated  in  the  thalamus  and  geniculate  body.  In  other  words, 
man's  position  in  the  scale  of  the  Animal  Kingdom  is  determined  by 
the  gradual  subordination  of  these  lower  centers  of  the  brain-stem 
to  the  more  recently  formed  cerebral  hemispheres  and  especially 
to  their  cortical  portions. 

This  functional  metamorphosis  displays  itself  in  an  increase  in  the 
complexity  of  the  brain  rather  than  in  an  increase  in  its  weight. 
Thus,  we  find  that  the  rabbit's  brain  presents  a  very  smooth  surface, 


THE  GENERAL  FUNCTION  OF  THE  CEREBRUM 


G07 


while  that  of  tlio  cat,  dos  and  ape  is  docidodly  uneven,  i.e.,  it  is  crossed 
by  furrow-hke  depressions  or  sulci  which  <  livide  it  into  numerous  convolu- 
tions and  lobes.  Its  greatest  complexity  it  attains  in  man,  butevenhere 
certain  differences  are  apparent  in  that  the  brain  of  the  more  prhnitive 


8.  fwnltUa  wuftnor 


poulerttrali*  ntp^riar 
S  t-traparutalia 


Ramus  ant.  ajcm 


JUmutpott-  of  Sylvian  f. 


S.  oceipilaii»  lateralit 

8.  occipitalu  trafttrtrtua 


Pjq    337.— Left  Cerebral  Hemisphere  from  the  Lateral  Aspect.     (/.  Symington.) 


F<una  d^y^UUa 


Pjq_  338.— Left  Cerebral  Hemisphere  from  the  Mesl4.l  Aspect. 
The  label  "caput  hippocampi"  has  been  placed  too  far  forward.     The  caput  hippo- 
campi does  not  extend  in  front  of  the  incisura  temporalis.     (./.  Symington.) 

races  is  poorer  in  convolutions  than  that  of  the  more  advanced  peoples. 
In  addition  to  these  external  differences,  we  are  also  able  to  make  out 
certain  internal  pecuUarities  which  pertain  chiefly  to  the  structure  of  the 


668  THE    CEREBRUM 

cortex.  In  the  rabbit,  for  example,  the  polymorphous  layer  displays  a 
thickness  three  times  greater  than  that  of  the  pyramidal  layer,  whereas 
in  man  just  the  reverse  relationship  exists.  The  inference  to  be  drawn 
from  this  is  that  the  p3'ramidal  cells  are  the  association  units  of  the 
brain,  excepting,  of  course,  the  cells  of  Betz  which  are  motor  in  their 
function,  while  the  polj-morphous  elements  are  concerned  with  the  lower 
types  of  function.  By  exclusion,  we  may  then  assign  a  sensory  func- 
tion to  the  constituents  of  the  granular  layer. 

This  analj'sis  should  also  take  into  account  that  the  ''psychic" 
l^rain  of  man  exhibits  certain  minor  differences  in  regard  to  the  relative 
size  and  complexity  of  its  different  association  areas.  One  or  the  other 
of  these  may  be  more  highly  developed  with  the  result  that  the  mechan- 
ism of  which  the  area  so  favored  forms  a  part,  possesses  a  greater 
functional  adaptability.  In  other  words,  it  frequently  happens  that 
these  association  centers  are  not  evenly  balanced.  It  need  scarcely 
be  emphasized  that  such  differences  may  also  be  displayed  by  one  and 
the  same  association  area  belonging  to  the  brains  of  different  indi- 
viduals, i.e.,  one  or  the  other  person  may  excel  in  certain  motor  or  sen- 
sory actions. 

Removal  of  the  Cerebrum. — The  preceding  discussion  may  well 
be  amplified  by  a  study  of  the  behavior  of  animals  which  have  suffered 
a  partial  or  complete  loss  of  the  cerebral  hemispheres  by  disease  or 
surgical  operation.  While  the  s^miptoms  appearing  subsequent  to  the 
latter  procedure  vary  somewhat  in  different  animals,  they  present 
nevertheless  the  same  general  characteristics.  The  essence  of  these 
changes  is  that  an  animal,  the  cerebrum  of  which  has  been  removed,  is 
devoid  of  associations.  Its  psychic  life,  whether  simple  or  complex, 
has  been  destroyed.  It  has  been  converted  into  a  simple  reflex  ma- 
chine. This  fact  will  be  brought  out  more  clearlj^by  a  brief  considera- 
tion of  the  functional  capabiHties  of  decerebrated  fish,  amphibia  and 
reptilia.  These  animals  are  selected  for  this  purpose  partly  because 
their  cerebrum  is  sufficiently  compact  and  easy  of  access  to  permit  of 
its  quick  removal,  and  partly  because  the  positive  results  following 
this  operation  are  so  few  that  they  do  not  overshadow  the  principal 
effect  briefly  alluded  to  above.  As  this  operation  is  performed  under 
ether,  these  animals  should,  of  course,  be  permitted  to  fully  recover 
before  they  are  studied. 

Emphasis  should  be  placed  upon  the  fact  that  the  loss  of  the 
cerebrum  destroys  the  sensorium.  The  decerebrated  bony  fish  (shark) ' 
shows  the  same  power  and  manner  of  movement  as  a  perfectly  normal 
animal.  It  tends,  however,  to  be  more  inactive,  assuming  a  rather 
continuous  position  of  rest  which  is  changed  to  one  of  activity  only 
upon  stimulation.  But  when  made  to  move,  its  motor  reactions  show 
no  deviation  from  normal.  More  decided  defects,  however,  appear 
when  the  lesion  is  extended  to  the  midbrain,  because  the  animal  then 
is  rendered  blind  and  loses  its  sense  of  equilibrium. 

'  Bandelet,  Ann.  d.  sc.  nat.,  105,  1864. 


THE  GENERAL  FUNCTION  OF  THE  CEREBRUM      GG9 

Quito  similarly,  a  clocorebratcd  frog'  shows  few  modifications  in 
its  behavior,  excepting  those  directly  referal)le  to  the  loss  of  the  sense 
of  smell.  It  retains  a  normal  posture  antl  jumps  and  swhns  normally. 
It  rights  itself  when  placed  upon  its  back,  and  executes  centrifugal 
and  balancing  motions  when  placed  upon  a  rotating  (Use.  Provided 
that  the  thalamus  has  not  been  injured,  it  avoids  obstacles  placed  in 
its  way,  and  reacts  to  stimuli  applied  to  the  nasal  mucous  membrane  by 
various  protective  movements.  These  reactions,  however,  it  shows 
only  when  stimulated.  Its  normal  attitude  is  one  of  inactivity,  be- 
cause it  has  lost  the  memory  of  past  experiences  and  instincts.  For 
this  reason,  it  need  not  surprise  us  that  an  animal  of  this  kind  takes  no 
food  but  must  be  fed;  in  fact,  the  food  must  be  placed  directly  into  its 
mouth.  The  processes  of  deglutition  and  digestion  are  in  no  way 
impaired,  and  hence,  it  is  possible  to  keep  this  animal  for  many  months 
or  even  for  years.  A  general  idea  regarding  the  function  of  the  cere- 
brum may  be  had  from  the  character  of  the  croaking  reflex  before  and 
after  the  removal  of  the  hemispheres.  Under  normal  conditions,  this 
act  is  a  complex  association  phenomenon;  i.e.,  this  sound  is  produced 
only  in  consequence  of  definite  cortical  processes,  and  is  under  the 
guidance  of  the  will.  In  the  absence  of  the  cerebrum,  on  the  other 
hand,  it  is  a  pure  reflex,  so  that  it  may  be  elicited  at  any  time  by  the 
proper  kind  of  stimulation  consisting  in  a  gentle  pressure  upon  the 
lateral  aspects  of  the  chest  and  abdomen.  Furthermore,  if  we  pass 
our  hand  over  a  number  of  normal  frogs,  these  animals  will  immediately 
make  motor  efforts  to  escape  from  the  area  of  stimulation,  while  the 
decerebrated  animals  will  not.  In  brief,  we  may  say  that  the  latter 
have  lost  their  associations  and  are  no  longer  under  the  control  of 
motives  or  sensations  of  fear. 

The  same  general  effects  are  manifested  by  birds^  when  deprived 
of  their  cerebral  hemispheres.  They  assume  a  position  of  rest,  generally 
upon  one  leg  with  the  head  drawn  in  and  the  bill  buried  in  the 
feathers.  Every  now  and  then  they  will  open  their  eyes,  stretch 
themselves,  and  walk  about  in  the  cage.  This  nonresponsive  attitude 
may  be  disturbed  at  any  time  by  stimulation,  i.e.,  the  animal  may 
be  made  to  fly  by  throwing  it  some  distance  into  the  air,  or  it  may  be 
made  to  execute  balancing  movements  upon  a  rope  swung  back  and 
forth.  It  will  right  itself  immediately  if  placed  upon  its  back,  and 
continues  to  move  about  if  made  to  do  so.  In  all  these  cases,  however, 
the  position  of  rest  is  sought  very  soon  after  the  stimulation  ceases. 
Its  reactions  are  machine-like,  and  are  executed  without  definite  purpose 
or  regard  to  environment.  This  is  well  shown  by  the  decerebrated 
pigeon  which,  when  made  to  fly,  soon  alights  upon  any  object  situated 
in  its  path  even  if  it  should  endanger  its  life.  As  all  its  digestive 
processes  and  spinal  reflexes  are  perfectly  normal,  this  pigeon  may  be 
kept  for  an  indefinite  period  of  time  provided,  of  course,  that  it  is 

^Blaschko,  Sehzentrum  der  Frosche,  Berlin,  1880. 
2  Bechterew,  Archiv  fiir  Physiol.,  1890,  489. 


670  THE    CEREBRUM 

fed  and  properly  attended  to.  In  fact,  its  initial  lethargy  is  partially 
compensated  for  in  time,  owing  to  the  gradual  development  in  the  lower 
centers  of  certain  activities  previously  suppressed. 

The  removal  of  the  cerebral  cortex  in  mammals  presents  several 
technical  difficulties  and  is  attended  by  certain  motor  and  sensory 
defects  which  do  not  permit  of  a  precise  analysis.  Still,  it  is  easily 
noted  that  this  operation  does  not  destroy  the  ordinary  spinal  and  basal 
reflexes  and  does  not  lead  to  a  complete  disarrangement  of  the  motor 
functions.  This  is  true  not  only  of  rabbits,  guinea  pigs,  and  cats,^ 
but  also  of  dogs.  Directly  after  the  operation,  these  animals  showed 
a  spastic  rigidity  of  their  extremities,  the  so-called  decerebrate 
rigidity,^  as  well  as  an  extensor  tonus  and  an  upward  deviation  of  the 
head,  or  opisthotonos.  These  symptoms  disappeared  in  the  course 
of  a  few  days,  whereupon  the  animal  was  capable  of  making  relatively 
precise  muscular  movements. 

The  dogs  of  Goltz^  were  operated  on  at  intervals  of  several  months, 
a  part  of  the  cerebrum  being  removed  each  time.  They  were  kept 
for  51  and  92  days  and  one  for  18  months.  On  autopsy  it  was  found 
that  they  had  retained  small  portions  of  the  striate  body,  optic  thala- 
mus and  uncus.  All  these  parts,  however,  were  soft  and  atrophic  and 
in  all  probability  functionally  useless.  The  anunals  began  to  move 
about  within  a  few  days  after  the  operation  and  even  walked  across 
inclined  planes.  They  rested  by  assuming  the  usual  position,  but 
could  not  be  kept  in  a  normal  nutritive  condition,  in  spite  of  the  fact 
that  they  were  rather  overfed.  They  reacted  to  sensory  stimuli 
by  snarHng,  barking  and  the  erection  of  the  ears,  but  not  in  a  way  to 
display  recognition  or  to  effect  an  intelligent  motor  response.  Their 
spinal  reflexes  remained  normal.  The  animal  which  was  kept  longest, 
finally  acquired  the  power  of  taking  food  without  being  helped, 
although  it  had  to  be  held  directly  under  its  nose.  Food  with  a  dis- 
agreeable taste  was  not  swallowed.  In  general,  therefore,  these  ani- 
mals displayed  the  same  defects  as  the  birds,  reptilia  and  amphibia, 
namely,  a  loss  of  understanding  and  memory  which  made  willful  and 
purposeful  motor  responses  impossible.  Only  the  simple  reflexes  were 
retained,  namely,  reactions  which  do  not  involve  complex  associations. 
The  condition  of  these  animals  was  one  of  general  imbeciUty. 

It  has  previously  been  emphasized  that  the  development  of  the 
cerebral  h^emispheres  in  the  higher  animals  leads  to  the  gradual 
transfer  of  at  least  a  part  of  the  motor  processes  to  this  reahn.  This 
impHes  that  they  are  finally  subjugated  to  the  activities  of  the  cortex. 
As  this  higher  control  must,  of  course,  be  most  complete  in  the  apes  and 
man,  it  may  be  inferred  that  the  destruction  of  parts  of  their  cere- 
brum must  give  rise  to  sjTnptoms  which  are  much  more  intense  and 
lasting  than  those  previously  noted  in  the  case  of  birds,  reptiUa  and 

1  Probst,  Jahrb.  fur  Psych,  und  Neurologie,  1904. 

2  Sherrington,  Phil.  Transactions,  London,  1896. 

3  Pfluger's  Archiv,  iii,  1892,  570. 


THE    GENERAL    FUNCTION    OF    THE    CEREBRUM  671 

amphibia.  It  appears,  however,  that  the  general  dechietions  then 
made,  also  hold  true  in  the  case  of  man.  We  know  this  from  a  study 
of  the  behavior  of  infants  born  with  cerebral  defects  as  well  as  from  a 
study  of  the  symptoms  following  accidental  injuries  to  the  cerebral 
cortex.  The  cases  of  inhei'it(!d  absence  of  the  cerebrum  or  anen- 
cephalus,  recorded  by  Vaschide  and  Vurpas^  as  well  as  by  Sternberg 
and  Latzko,-  have  shown  that  the  spinal  reflexes  are  preserved  and  that 
muscular  movements  are  possible,  and  especially  those  concerned  with 
mastication,  sucking,  crying  and  grasping.  The  anencephalous  infant 
described  more  recently  by  Edinger  and  Fischer,''  lived  for  nearly  four 
years.  At  autopsy  it  was  shown  that  its  cerebral  hemispheres  had  been 
displaced  by  fluid ,  creating  a  condition  similar  to  hydrocephalus.  During 
this  time  it  showed  no  signs  of  intelligence,  but  its  motor  defects 
were  so  slight  that  even  its  mother  did  not  believe  that  anything  was 
wrong  with  it  until,  when  about  two  and  a  half  years  old,  it  began 
to  show  extensive  contractures  and  absolute  lethargy. 

The  destruction  of  considerable  portions  of  the  brain  does  not 
prove  fatal  as  a  rule  unless  the  injury  extends  beyond  the  cortex  of  the 
anterior  and  central  convolutions.  In  fact,  the  superficial  region  of 
one  whole  hemisphere  may  be  rendered  functionally  useless  without 
terminating  the  life  of  the  individual.  A  procegs  of  gradual  exclusion 
of  the  cerebral  cortex  is  at  work  in  advanced  stages  of  insanity,  when 
the  psychic  life  is  terminated  more  and  more  until  the  human  body 
is  finally  reduced  to  a  machine-like  reflex  existence,  effected  with  the 
help  of  the  more  deeply  seated  subsidiary  centers. 


CHAPTER  LV 

CEREBRAL  LOCALIZATION 

THE  MOTOR  AREA 

The  Functional  Separation  of  the  Cerebral  Cortex. — The  doctrine 
that  consciousness  in  its  various  aspects  is  the  product  of  several 
individualized  functions  of  the  brain,  was  first  developed  by  Galenus 
(131-203  A.D.),  although  the  cerebral  hemispheres  have  really  been  re- 
garded as  the  material  basis  of  consciousness  since  the  time  of  Hippo- 
crates (460-377  B.C.).  In  fact,  it  is  claimed  that  this  view  was  first 
expressed  by  Alkmeon  of  Croton  in  about  the  year  500  B.C.  The 
imaginative  qualities  were  said  to  be  seated  in  the  frontal,  intelligence 
in  the  central,  and  memory  in  the  posterior  regions  of  the  cerebrum. 
This  conception  that  consciousness  is  composed  of  separate  units  and 

1  Compt.  rend,  de  I'acad.,  cxxxii,  1901. 

2  Deutsche  Zeitschr.  fiir  Nervenheilk.,  xxiv,  1903,  209. 

3  Pfliiger's  Archiv,  clii,  1913,  535. 


672  THE    CEREBRUM 

that,  therefore,  the  cerebral  cortex  is  divisible  into  several  minor  or- 
gans, has  been  made  use  of  bj-  Gall,^  a  physician  of  Vienna,  in  framing 
his  system  of  cranioscopy,  or,  as  it  was  called  later  on  by  Spurzheim, 
the  science  of  phrenology.  Being  of  the  firm  belief  that  the  psychical 
power  of  an  individual  is  seated  in  the  cerebrum,  he  outlined  definite 
areas  upon  the  external  surface  of  the  cortex  in  accordance  with  defi- 
nite mental  qualities.  This  localization  he  based  upon  a  stud}'  of  the 
external  characteristics  of  the  cranium  of  people  who  showed  especially 
well-marked  mental  faculties.  He  reasoned  that  the  cerebral  area 
controlling  a  certain  function  must  increase  in  volume  in  proportion  to 
the  state  of  development  of  the  latter;  moreover,  this  internal  change 
must  betray  itself  in  a  greater  prominence  of  the  skull  plate  of  this 
•particular  area.  While  this  deduction  is  in  general  correct.  Gall 
carried  it  too  far,  and  was  in  no  position  to  furnish  experimental 
proof  for  his  assertions.  These  facts  were  subsequently  exploited 
for  commercial  purposes  and  no  definite  scientific  good  was  derived 
from  them,  at  least,  not  immediately. 

This  assumption  of  Gall  that  the  cerebrum  is  not  a  single  organ  or 
functional  unit,  was  first  criticised  b}^  Flourens,^  and  his  followers 
]\Iagendie,  Longet,  Budge  and  Schiff.  It  was  finally  pointed  out  that 
the  mental  life  of  man  cannot  be  subdivided  into  a  series  of  independent 
faculties,  this  conclusion  being  based  upon  the  theoretical  and  experi- 
mental data  of  different  writers.  Thus,  Flourens  showed  that  the 
destruction  of  the  cerebrum  of  pigeons  is  followed  by  a  loss  of  intelh- 
gence  which  it  is  impossible  to  grade  by  a  partial  destruction  of  this 
organ.  In  other  words,  the  successive  removal  of  certain  parts  of  the 
cerebrum  did  not  give  rise  to  a  progressive  series  of  psychic  defects, 
but  to  a  uniform  lowering  of  the  sum  total  of  the  psychic  processes. 
This  inability  to  localize  certain  functions  in  definite  areas  of  the 
cortex  led  him  to  believe  that  the  cerebral  hemispheres  act  as  a  uni- 
form whole  and  produce  the  phenomena  of  consciousness  jointly. 
This  conclusion  found  substantiation  in  the  symptoms  displayed  by 
individuals  who  had  suffered  accidental  injuries  of  the  brain.  It  will 
be  shown  later  on  that  this  conception  of  Flourens  is  correct  only  in 
part,  because  subsequent  researches  have  proved  beyond  doubt  that 
there  is  a  distinct  difference  in  the  functions  of  the  different  parts  of 
the  cerebrum,  or  rather  in  the  quality  of  the  contribution  which  they 
severally  make  to  consciousness.  Flourens,  however,  was  correct  in 
his  belief  that  the  psychic  life  is  really  dependent  upon  a  proper 
functional    interaction    of    the    different    constituents    of    the    brain. 

This  doctrine  of  Flourens  was  commonly  accepted  until  Broca 
(1861)  gave  final  proof  of  the  fact  that  the  loss  of  speech  so  frequently 
associated  with  apoplexy,  is  due  to  the  destruction  of  the  left  inferior 

1  Recherches  sur  la  syst.  nerv.  en  general  et  sur  celui  du  cerveau  en  particulier, 
1810. 

"  Rechersches  experimentales  sur  les  proprietes  et  les  fonctions  du  sj-st.  nerv. 
dans  les  animaux  vertebres,  1824. 


CEREBKAL    LOCALIZATION  073 

frontal  convolution.  This  conclusion  was  based  in  part  upon  the 
earlier  work  of  Bouillaud  (LS'i'))  which  tends  to  show  that  the  spee(^h 
center  is  situated  in  tlie  anterior  extnuTiities  of  the  frontal  lobes. 
Furthermore,  it  was  proved  by  M.  Dax  and  G.  Dax  (1836)  that  in 
right-handed  people  this  area  is  confined  to  the  left  cerebral  hemisphere. 
Attention  has  also  been  called  repeatedly  to  the  observation  of  Galenus 
that  a  paralysis  of  the  l)ody  i-esults  in  consequence  of  lesions  to  the  cere- 
bral hemisphere  of  the  opposite  side.  These  data,  however,  were 
not  considered  of  sufficient  importance  until  Broca  called  special 
attention  to  them. 

In  1864  H.  Jackson,  stimulated  by  the  work  of  Broca,  proved  that 
the  muscular  spasms  characterizing  epilepsy,  are  due  to  an  excitation 
of  the  cerebral  cortex.  A  firm  basis  was  given  to  this  view  in  1870 
by  Fritsch  and  Hitzig,^  who  showed  that  the  cortex  of  the  cerebrum 
is  irritable  and  that  its  stimulation  evokes  perfectly  definite  muscular 
responses.  These  tests  were  first  made  upon  dogs,  but  were  later  on 
extended  to  other  animals  and  also  to  the  apes  and  man  by  Ferrier, 
Horsley,  Schaffer,  Sherrington,  Luciani,  and  others.  As  a  direct 
result  of  this  work,  we  find  a  complete  abandonment  of  the  doctrine 
of  Flourens  and  the  acceptance  of  a  view  which  may  be  said  to  be  more 
directlj^  in  line  with  the  conception  of  Gall.  As  has  been  pointed 
out  above,  the  latter  regarded  the  cerebrum,  as  a  plurality  of  organs. 
In  its  modified  form  this  doctrine  holds  that  the  cerebrum  is  composed 
of  circumscribed  areas  possessing  different  sensory  and  motor  func- 
tions. Emphasis  is  placed  upon  the  fact  that  these  parts  are  not 
separated  from  one  another,  but  are  intimately  associated  and  inter- 
related with  one  another  so  as  to  jaeld  coordinated  function.  This 
fundamental  conception  is  in  no  way  altered  by  the  doctrine  of  Flechsig 
(1894)  which  asserts  in  addition  that  the  different  areas  of  the  cerebral 
cortex  consist  of  projection  and  association  fields.  In  other  words, 
the  different  cerebral  spheres  seem  to  be  built  up  of  a  central  core 
and  a  peripheral  zone  which  possesses  a  true  psychic  character. 

The  Location  of  the  Motor  Area. — The  discovery  of  Fritsch  and  Hit- 
zig,  that  the  cortex  of  the  brain  is  irritable,  completely  overthrew  the 
old  conception  of  Haller,  which  assumed  that  only  the  underlying 
white  matter  is  pervious  to  stimuli.  The  latter  view  prevailed  for  so 
long  a  time,  because  it  was  advocated  by  such  experimenters  as  Mag- 
endie,  Longet,  Mateucci,  Budge  and  Schiff,  and  was  based  chieflj^  upon 
their  inabihty  to  evoke  motor  reactions  by  the  stimulation  of  any  area 
of  the  cerebral  surface.  As  Fritsch  and  Hitzig  made  use  of  the  galvanic 
current,  which  tends  in  time  to  induce  electrotonic  alterations,  their 
localization  left  much  to  be  desired.  They  showed,  however,  that 
the  muscular  effects  are  confined  to  the  opposite  side  of  the  body 
and  may  be  varied  in  their  intensity  by  changing  the  strength  of  the 

1  Arch,  fur  Anat.  und  Physiol.,  1870,  300. 
43 


674 


THE    CEREBRUM 


current.     The  finer  details  were  brought  out  subsequently  by  Ferrier' 
by  means  of  faradic  stimulation. 

The  motor  area  is  situated  along  the  fissure  of  Rolando  (sulcus 
cruciatus)  of  each  hemisphere  and  occupies  the  anterior  and  posterior 
central  convolutions.  Each  area  is  composed  of  a  number  of  motor 
points,  so-called,  because  their  stimulation  with  fine  electrodes  gives 
rise  to  contractions  of  only  one  particular  muscle  or  group  of  muscles. 
In  mapping  out  this  field,  it  is  also  to  be  noted  that  these  motor  points 
are  arranged  in  a  definite  manner,  those  governing  the  activity  of  the 
muscles  of  the  trunk  being  situated  very  close  to  the  longitudinal 
fissure,  and  those  controlling  the  posterior  extremity  upon  the  upper- 


Fig.  339. — Lateral  View  of  the  Brain  of  a 
Dog.  Diagram  Indicating  the  Location  of  the 
Motor  Area. 

CS,  Crucial  sulcus;  T,  L,  A  andF,  areas  for 
the  muscles  of  the  trunk,  leg,  arm  and  face. 


Fig.  340. — Diagram  Showing 
THE  Motor  Points  in  the  Cere- 
brum of  THE  Dog. 


most  convexity  of  the  cerebral  surface.  Directly  below  this  field  we 
find  the  motor  points  for  the  anterior  extremity  and  at  a  still  lower 
level  those  for  the  facial  muscles.  In  general,  therefore,  it  may  be 
stated  that  each  motor  area  is  composed  of  four  minor  fields  which 
control  respectively  the  movements  of  the  trunk,  leg,  arm,  and  face. 
Each  minor  field  is  subdivided  in  turn  into  still  smaller  ones,  the  so- 
called  motor  points. 

This  finer  subdivision  of  the  motor  areas  is  not  apparent  in  such 
mammals  as  the  rabbit,  cat,  and  dog,  but  becomes  unmistakable  in  the 
monkeys  and  reaches  its  highest  development  in  the  apes  and  man. 
While  only  very  general  reactions  can  be  evoked  in  rabbits,  the  cat  and 
dog  show  movements  of  a  more  specialized  character.  This  may  be 
gathered  without  difficulty  from  the  preceding  Fig.  340,  illustrating 


1  Les  fonctions  du  cerveau,  Paris,  1878. 


CEREBRAL    LOCALIZATION 


675 


the  position  and  functional  character  of  the  motor  points  in  the  do^. 
It  is  to  be  noted  especially  that  they  are  situated  on  both  sides  of  the 
crucial  sulcus  and  are  sufficiently  centralized  to  permit,  for  example, 
the  separate  activation  of  the  flexors  of  the  anterior  and  posterior 
extremities  and  other  rather  specialized  movements,  such  as  the  re- 
traction and  abduction  of  the  fore  limbs,  movements  of  the  tail,  closure 
of  the  eyelids,  constriction  of  the  pupils,  movements  of  deglutition,  and 
others. 

The  movements  themselves  are  in  no  way  diiTerent  from  those 
produced  in  the  course  of  the  normal  volitional  efforts  of  the  animal. 


Hip 


Eyelid   /Closure     \  ^CL    \^^Sule us  Centralis 

Alose    ^J'''^  opening  Vocdt    Mastication, 
of-f<li*>     cords 

Fig.  341. — Location  of  Motor  Areas  in  Brain  of  Chimpanzee. 
The  different  motor  points  lie  in  front  of  the  fissure  of  Rolando,  partly  within  the 
sulci.     The  area  marked    "eyes"    yields    conjungate   movements   of   the   eyes,    but   is 
generally  not  taken  to  be  a  part  of  the  motor  area.      (Sherrington  and  Greenbaum.) 

This  impHes  that  they  are  never  antagonistic  to  one  another,  for  the 
reason  that,  having  evoked  a  contraction  of  the  flexors,  the  extensors 
are  momentarily  inhibited,  and  vice  versa.  This  preponderance  of 
one  set  of  muscles,  even  when  the  stimulation  involves  the  motor  points 
of  both  groups,  may  be  destroyed  by  rendering  the  nervous  structures 
more  irritable  by  means  of  strychnin  or  the  toxin  of  tetanus.  Under 
this  condition  the  cerebral  stimulation  spreads,  activating  the  entire 
reciprocal  mechanism.  We  then  obtain  a  strife  between  the  antagonis- 
tic muscles  with  the  result  that  the  stronger  ones  predominate. 

As  has  been  emphasized  above,  the  effect  of  the  stimulation  of 
the  motor  area  is  unilateral,  and  is  restricted  to  the  side  opposite  the 
excitation.  There  is  one  exception  to  this  rule  and  that  is  conjugate 
movement.     Thus,  it  will  be  noted  that  the  stimulation,  say  of  the 


676 


THE    CEREBRUM 


right  motor  points  controlling  the  muscles  of  the  eyes,  produces  a 
deviation  of  both  eyes  toward  the  left.  In  this  case,  therefore,  an 
activation  of  the  right  int-ernal  and  left  external  recti  results  which 
is  associated  with  an  inhibition  of  the  right  external  and  left  internal 
recti.  The  same  holds  true  of  other  movements  which  are  carried 
on  with  the  help  of  corresponding  muscles  on  the  two  sides  of  the 
body,  such  as  the  erection  and  flexion  of  the  trunk,  the  approximation 
of  the  jaws,  and  the  contraction  of  the  muscles  of  the  abdominal  wall. 
Clearly,  these  movements  must  ])e  bilaterally  controlled  and  coordi- 
nated. A  bilateral  representation  is  also  had  in  the  case  of  the  respi- 
ratory muscles,  because,  as  will  be  pointed  out  later,  the  destruction 
of  one  motor  area  does  not  affect  the  respiratory  movements. 

The  observations  of  Sherrington  and  Greenbaum^  have  shown  that 
in  the  anthropoid  apes  the  motor  area  is   confined  to  the  anterior 


Sulc.  Central.      ^^'^^  *  f^'^g/na. 


Sulccatloso 

Sulc.parieCo 
ocdp. 


Sulc.precentr.vuirg- 


Sulccalcarin 


C.3.S.  del. 


Fig.  342. — Mesial  Surface  of  Chimpanzee,   Showing  that  the   Motok  Areas  also 
Dip  into  the  Longitudinal  Fissure.      {Sherrington  and  Grecnbaum.) 

central  convolution,  but  this  discovery  is  not  wholly  new,  because 
a  very  similar  condition  has  already  been  proved  by  Fritsch  and  Hitzig 
to  exist  in  the  monkey.  These  tests  have  been  extended  to  man  by 
Bartholowand  Sciamanna,  but  particularly  by  Ferrier  (1890),  Horsley, 
Brevior  (1890),  and  Bechterew  (1899).  The  more  recent  work  of  F. 
Krause^  in  particular  tends  to  prove  that  the  localization  in  man  is 
very  similar  to  that  found  in  the  anthropoid  apes.  The  motor  points 
are  concentrated  in  the  precentral  convolution  and  neighboring  por- 
tions of  the  frontal  furrows  and  permit  of  the  production  of  very 
specialized  movements. 

The  Motor  Area  is  a  True  Center.^ — Fritsch  and  Hitzig  character- 
ized the  motor  area  as  a  center  for  the  production  of  muscular  motion. 

^  Proc.  Royal  Soc,  London,  Ixxii,  1903. 

*  Lewandowsky,  Die  Funktionen  des  zentralen  Nervensystems,  Jena,  1907. 


CEREBRAL   LOCALIZATION  677 

This  conception  is  correct,  because  it  has  subsequently  been  shown 
that  the  stimulus  arises  in  the  gray  matter  of  the  cerebral  cortex  and 
not  in  the  fibers  leading  away  from  this  area.  This  is  proved  by  the 
fact  that  the  latent  period,  i.e.,  the  time  elapsing  between  the  moment 
of  the  application  of  the  stimulus  and  the  l^eginning  of  the  muscular 
movement,  is  longer  when  the  stimulus  is  applied  to  the  surface  of  the 
gray  matter  than  when  brought  to  bear  directly  upon  the  underlying 
white  matter.  This  result  clearly  betrays  the  controlling  influence  of 
the  cells  composing  this  area.  Central  formative  processes  always 
consume  a  much  longer  time  than  the  mere  passage  of  the  impulses 
over  nerve-tissue.  In  addition,  it  has  been  proved  that  the  gray  matter 
possesses  a  lower  threshold  value  of  stimulation  than  the  white  matter. 
In  other  words,  a  lesser  strength  of  current  is  required  for  its  activation 
than  for  that  of  the  underlying  fiber  substance.  This  relationship, 
however,  may  be  reversed  by  painting  the  cerebral  surface  with  cocain 
or  chloral.^ 

In  this  connection  it  should  be  stated  that  muscular  movements 
may  also  be  evoked  by  the  stimulation  of  very  restricted  areas  of  the 
occipital  and  temporal  lobes.  These  movements,  however,  remain 
confined  to  the  extrinsic  muscles  of  the  eyes  and  ears  and  seem,  there- 
fore, to  be  the  direct  outcome  of  the  psychic  processes  occurring  in 
these  particular  areas.  The  impulses  here  generated  are  transferred 
first  of  all  to  the  motor  area  in  the  precentral  convolution  and  later 
on  to  the  distant  motor  organs.  Hence,  neither  the  occipital  nor  the 
temporal  lobes  should  be  regarded  as  true  motor  centers,  although 
both  are  in  a  position  by  means  of  close  association  paths  to  activate 
the  chief  motor  center  in  the  anterior  central  region. 

Traumatic  Epilepsy. — It  has  previously  been  stated  that  the 
muscular  spasms  associated  with  epileptic  seizures,  have  been  attributed 
by  Jackson-  (1864)  to  a  mechanical  irritation  of  a  particular  area  of 
the  cerebral  cortex.  This  assertion,  which  was  made  sometime  before 
the  publication  of  the  work  of  Fritsch  and  Hitzig,  was  based  upon  the 
fact  that  certain  types  of  epileptics  present  definite  lesions  of  the  cere- 
bral gray  matter.  A  few  years  later  it  found  confirmation  in  the  ob- 
servation of  Fritsch  and  Hitzig  proving  that  the  application  of  a  strong 
galvanic  current  to  the  surface  of  the  motor  region  gives  rise  to 
powerful  and  lasting  muscular  contractions.  Ferrier,  Luciani  and 
Unverricht^  showed  subsequently  that  these  seizures  need  not  remain 
localized,  but  may  acquire  a  progressive  character  until  they  involve 
the  musculature  of  practically  the  entire  body.  So  generalized,  they 
constitute  the  clinical  picture  which  is  commonly  seen  during  the  con- 
vulsive seizures  of  epileptics.  It  is  true,  however,  that  an  increase 
in  the  strength  of  the  current  is  not  the  only  means  by  which  these 

1  Francois — Frank  and  Pitres,  Arch,  de  Physiol,  norm.  et.  path.,  1883. 
*  Hitzia;,   H.   Jackson  und  die  motor.   Rindenzentren  im  Lichte  der  physiol. 
Forschiing,  Berlin,  1901;  also:  H.  Jackson,  A  Study  of  Convulsions,  London,  1870. 
3  Archiv  fur  Psychiatric,  xiv,  1880,  175. 


678  THE    CEREBRUM 

general  seizures  may  be  evoked.  In  many  cases  even  weak  stimuli 
suffice,  provided,  of  course,  that  the  nervous  system  has  been  rendered 
especially  susceptible.  Conditions  of  this  kind  often  arise  in  the 
course  of  eclampsia,  uremia,  and  diabetes,  after  the  toxins  contained 
in  the  blood  have  led  to  a  constant  discharge  of  supraminimal  im- 
pulses. Thus,  Landois^  has  succeeded  in  evoking  tonic  and  clonic 
spasms  by  spraying  the  motor  areas  with  creatin,  creatinin  and  urates. 
The  same  results  may  be  obtained  with  such  agents  as  santonin, 
physostigmin  and  bile,  and  even  more  readily  in  pregnant  animals,^ 
in  which  the  nervous  system  is  in  an  especially  irritable  condition. 

Traumatic  or  Jacksonian  epilepsy  most  commonly  finds  its 
origin  in  tumors  or  in  the  pressure  exerted  upon  the  motor  area  by  the 
projecting  pieces  of  bone  of  an  old  fracture.  These  seizures  are 
ushered  in  as  a  rule  by  a  feeling  of  numbness  and  a  tingling  sensation 
in  the  part  to  be  affected  first.  Thus,  if  the  motor  points  of  the 
muscles  of  the  thumb  are  the  seat  of  the  excitation,  the  contractions 
begin  in  this  part  and  then  spread  to  the  muscles  of  the  hand,  forearm, 
arm  and  shoulder,  and  later  on  to  those  of  the  face,  trunk  and  leg. 
Eventually  they  also  involve  the  muscles  of  the  opposite  side  of  the 
body.  This  orderly  sequence  or  "march"  is  also  observed  if  the 
contractions  begin  with  the  muscles  of  the  toes  or  foot.  When  these 
seizures  are  reproduced  in  animals,  it  is  quite  impossible  to  prevent 
the  spreading  of  the  contractions  from  one  side  of  the  body  to  the 
other  by  cutting  the  corpus  callosum.  Single  muscles,  however, 
may  be  prevented  from  participating  in  the  general  convulsion  by 
ablation  of  the  corresponding  motor  district.  It  seems,  therefore,  that 
the  aforesaid  spreading  is  made  possible  through  the  mediation  of  the 
subcortical  paths  and  centers. 

These  seizures  may  last  a  few  seconds  or  several  minutes.  They 
consist  as  a  rule  of  a  tonic  and  a  clonic  phase.  To  begin  with,  the 
muscles  remain  tonically  set,  but  presently  show  repeated  attempts  at 
relaxation.  These  relaxations  are  separated  from  one  another  at  first 
by  intervals  of  several  seconds,  but  gradually  become  more  frequent 
toward  the  end  of  the  convulsion.  In  consequence  of  these  violent 
muscular  contractions,  the  body  temperature  most  generally  shows  a 
rise  of  several  degrees,  but  consciousness  is  not  lost  unless  the  attack 
is  severe.  This  fact  really  serves  as  one  of  the  differential  signs  between 
Jacksonian  and  idiopathic  epilepsy.  The  latter  is  a  type  of  epilepsy 
which  must  be  assigned  to  general  retrogressive  changes  of  the  cortex. 
It  need  scarcely  be  mentioned  that  the  traumatic  type  may  be  remedied 
by  removing  its  cause,  the  seat  of  the  lesion  being  suggested  by  the 
manner  of  progression  of  the  muscular  contractions.  For  example, 
if  the  epileptic  seizure  begins  with  tonic  and  clonic  spasms  of  the 
muscles  of  the  thumb,  it  is  to  be  inferred  that  the  difficulty  chiefly 

1  Wiener  med.   Presse,   1887. 

2  Bickel,  Pfluger's  Archiv,  Ixxii,  1898,  190,  also :  Blumenreich  and  Zuntz,  Arch, 
fur  Physiol.,  1901. 


CEREBRAL    LOCALIZATION  679 

involves  the  motor  points  of  this  jxirticular  part.  The  location  of 
the  trephine  opening  may  then  he  detcrniined  with  almost  mathe- 
matical precision. 

Efifects  of  the  Ablation  of  the  Motor  Area. — In  dogs,  the  destruc- 
tion of  one  motor  area  results  in  an  incomplete  paralysis  of  the  muscles 
of  the  opposite  side  of  the  body.  This  condition  is  known  as  hemi- 
plegia, the  term  biplegia  being  used  when  both  sides  are  affected. 
While  this  muscular  disturbance  usually  attains  its  height  within  a  few 
hours  after  the  injury,  it  gradually  becomes  less  acute  later  on  and 
ilisappears  in  the  course  of  a  few  days.  During  the  interim,  however, 
the  dog  betrays  a  decided  weakness  of  the  muscles  situated  on  the  side 
opposite  to  the  injury,  and  generally  walks  upon  the  back  of  the  paws. 
Furthermore,  those  muscles  which  usually  act  together,  never  exhibit 
so  decided  a  degree  of  paralysis  as  those  which  are  not  directly  related. 


Fig.  343. — DL\GR.\ii  Illustr.\ting  the  Disposition  of  the  Motor  axd  Sexsokt  Poixts 
IN  THE  Brain  of  the  Dog  (A)  and  the  Brain  of  the  Monkey  (B). 
In  the  former  animal  motor  and  sensory  paralysis  generally  occur  together,  because 
their  points  intermingle,  while  in  the  apes  and  man  they  do  not. 

Consequently,  the  muscles  of  respiration  and  those  of  the  trunk  in  gene- 
ral are  weakened  but  never  paralyzed.  This  fact  indicates  that  they 
are  innervated  by  both  hemispheres. 

These  motor  disturbances  are  associated  as  a  rule  with  a  very 
decided  loss  of  the  tactile  sensations  and  the  muscle  sense.  It  ap- 
pears, therefore,  that  the  motor  area  of  the  dog,  i.e.,  the  anterior 
and  posterior  central  convolutions  of  each  side,  also  embraces  certain 
sensory  points,  representing  the  end  stations  of  the  incoming  fibers 
pertaining  to  these  sensations  (Fig.  343).  This  intermingling  of  the 
motor  and  sensory  points,  however,  is  not  in  evidence  in  the  monkeys, 
apes  and  man.  It  will  be  shown  later  on  that  in  these  animals  the 
former  are  concentrated  more  and  more  in  the  precentral  and  the  latter 
in  the  postcentral  convolution,  inclusive  of  the  neighboring  region  of 
the  parietal  lobe.  Hence,  it  is  possible  to  obtain  in  these  animals 
a  motor  paralysis  which  is  not  accompanied  by  disturbances  of  sen- 
sation. Conversely,  they  may  show  sensory  anesthesias  without  loss 
of  motion. 


680  THE    CEREBRUM 

In  the  monkey,  the  ablation  of  the  motor  area  gives  rise  to  very- 
marked  and  permanent  sjonptoms.  Very  instructive  observations 
have  been  made  by  Goltz  upon  macacus  whose  left  frontal  and  parietal 
cortex  had  been  removed  by  two  operations.  The  animal  remained 
under  observation  for  eleven  years.  The  decided  hemiplegia  fol- 
lowing directly  after  the  operation,  gave  way  in  the  course  of  two 
months  to  a  more  moderate  paralysis  of  the  muscles  of  the  right  side. 
This  disturbance,  however,  persisted  so  that  the  animal  always  retained 
a  certain  clumsiness  of  movement.  It  also  showed  certain  sensory 
defects  for  the  obvious  reason  that  the  lesion  also  involved  the  post- 
central and  parietal  gj^ri.  In  walking,  climbing  and  j  umping  the  muscles 
of  the  left  side  were  always  relied  upon  most;  in  fact,  unless  made  to 
use  the  right  hand,  the  animal  preferred  to  employ  the  left  hand.  It 
appears,  therefore,  that  the  motor  area  of  the  monkey  is  of  much 
greater  functional  importance  than  that  of  the  dog  for  the  reason 
that  it  is  concerned  with  those  higher  forms  of  movements  which 
can  only  be  acquired  by  training  and  experience.  Obviously,  it  is  more 
difficult  to  reestablish  a  center  for  skilled  movements  than  it  is  to 
compensate  for  the  loss  of  a  center  controlling  the  less  specialized 
movements  of  the  dog.  This  deduction  is  in  complete  harmony 
with  the  greater  specificity  of  the  pyramidal  system  of  the  higher 
animals  as  well  as  with  the  fact  that  the  motor  functions  of  the  latter 
have  gradually  been  brought  under  the  control  of  the  cerebral  hemi- 
spheres. This  is  true  especially  of  man  in  whom  almost  all  muscular 
actions  are  dominated  by  the  cerebrum.  It  need  scarcely  be  em- 
phasized that  this  higher  innervation  necessitates  experience  and 
education,  two  processes  which  are  not  essential  to  the  lower  forms, 
because  their  actions  are  largely  determined  by  subcortical  centers. 
For  this  reason  we  cannot  be  surprised  at  the  helplessness  of  infants 
as  against  young  animals  much  lower  in  the  scale  of  the  Animal 
Kingdom. 

In  further  analysis  of  this  subject  matter  it  may  be  inferred  that  the 
recovery  from  lesions  of  the  motor  area  must  be  least  complete  in 
man.  The  histories  of  such  cases  show  that  this  injury  is  invariably 
followed  by  a  contralateral  paralysis,  the  extent  of  which  is  propor- 
tionate to  the  size  and  severitj^  of  the  central  defect.  Moreover,  in 
those  cases  in  which  the  lesion  remains  confined  to  the  anterior  central 
convolution,  no  true  sensory  disturbance  arises. "^  It  is  also  to  be 
observed  that  the  parah^sis  involves  chiefly  those  muscles  which 
are  under  the  guidance  of  the  will  and  are  not  paired  in  function. 
In  other  words,  the  muscles  of  respiration,  such  as  the  diaphragm, 
the  abdominal  and  intercostals  and  those  of  the  larynx,  are  excepted. 
While  a  certain  recovery  from  the  immediate  effects  of  the  lesion  may 
take  place  in  the  course  of  time,  hemiplegic  muscles  never  regain  their 
normal  usefulness. 

It  has  been  mentioned  above  that  hemiplegia  is  frequently  asso- 

1  ]\Ionakow,  Ergebn.  der  Physiol.,  1902. 


CEREBRAL    LOCALIZATION  681 

ciated  wath  contractures  of  the  paralyzed  muscles,  while  paraplegia 
n^sulting  in  consequence  of  the  division  of  the  spinal  cord  or  higher 
conducting  paths,  is  not.  This  hypertonic  setting  of  the  muscles 
may  be  explained  by  the  assumption  that  the  injury  to  the  cerebrum 
has  removed  those  inhibitory  impulses  which  ordinarily  tend  to  hold 
the  tonic  discharges  of  the  ganglion  cells  in  check.  In  consequence  of 
this  removal  of  cerebral  inhibition  the  lower  reflexes  have  full  sway 
and  are  enabled  to  play  upon  these  muscles  repeatedly  until  they 
are  thrown  into  a  state  of  spastic  rigidity  or  contracture.  "High" 
lesions,  therefore,  increase  the  spinal  reflexes,  while  "low"  lesions  tend 
to  diminish  them,  thereby  allowing  the  muscles  to  remain  continuously 
in  a  flaccid  condition. 

The  foregoing  discussion  should  also  have  made  it  clear  that  the 
motor  area  constitutes  a  center  for  voluntary  movements.  This 
statement,  however,  does  not  imply  that  this  area,  in  conjunction  with 
the  faculty  of  volition,  is  the  primary  exciting  agent  of  all  muscular 
movements.  A  conclusion  of  this  kind  cannot  be  correct  for  the  reason 
that  all  our  actions  result  in  consequence  of  sensory  impressions,  and 
are,  therefore,  not  spontaneous.  As  the  motor  area,  together  with  the 
pyramidal  system,  forms  merely  the  efferent  arc  of  the  association  or 
reaction  circuit  necessary  for  motion,  it  cannot  be  regarded  as  a  thor- 
oughly independent  unit  capable  of  generating  centrifugal  impulses 
unaided.  The  afferent  impulses  and  subsequent  sensory  impressions 
ordinarily  responsible  for  the  activation  of  this  motor  system,  are 
derived  from  the  different  association  centers  of  the  cerebrum  with 
which  we  will  become  acquainted  in  the  chapter  now  following. 


CHAPTER  LVI 


CEREBRAL  LOCALIZATION  (CONTINUED) 

THE  BODY -SENSE  AREA 

The  Location  of  the  Body-sense  Area. — While  it  is  undoubtedly 
true  that,  in  the  lower  animals,  the  sensory  and  motor  areas  overlap 
to  such  an  extent  that  it  has  been  suggested  by  Bastian  to  apply 
to  them  the  more  general  term  of  kinesthetic  area,^  the  more  recent 
experimental  work  has  shown  that,  in  the  apes  and  man,  these  fields 
find  a  natural  boundary  in  the  fissure  of  Rolando.  ^  Thus,  it  is  now 
commonly  accepted  that  the  motor  area  lies  in  front  of  this  sulcus  and 
the  sensory  area  posterior  to  it.  It  must  be  evident,  therefore, 
that  a  hemiplegia  need  not  be  associated  with  a  hemianesthesia,  unless 

1  Luciani  and  Seppilli,  Le  Localsizzazioni  funz.  del  cervello,  Napoli,  1885. 

2  Von  Monakow,  Ergebn.  der.  Physiol.,  1902. 


682 


THE    CEREBRUM 


the  lesion  also  involves  the  posterior  Rolandic  region.  Hence,  an 
injur\^,  involving  the  entire  centro-parietal  field,  must  always  be  ac- 
companied by  a  loss  of  cutaneous  sensation. 

iMonakow  does  not  give  a  definite  boundary  for  this  sensory  region, 
but  merely  states  that  it  embraces  the  posterior  central  gyrus  and  the 


TE.nPOR'^^ 


B 


1NTERME.01ATE  4-  o^ 

POSTCENTRALS         <P, 


EOIATE  PRECENTRAU 


Fig.   .344. — Human  Brain  Showing  Outer   (A)  and   Mzsial   {Bi    Surfaces,  and  the 
Situation  of  the  Chief  Motor  ant)  Sensory  Areas. 
The  different  shading  represents  the  extent  of  each  of  these  areas  as  determined  by  a 
study  of  the  histological  structure  of  the  cortex.      (Campbell.) 

anterior  realm  of  the  superior  to  inferior  convolutions  of  the  parietal 

lobe.     Flech.sig's  view^  coincides  with  this  localization.     He  especially 

emphasizes  the  fact  that  the  sensor}-  points  are  centralized  in  the  con- 

*  Sachs.  Gesellsch.  der  Wissenschaften,  Leipzig,  1904. 


CEREBRAL    LOCALIZATION 


083 


vcxity  of  the  postci'ior  central  convolution,  while  the  Rolandic  sulcus 
itself  is  already  i)artly  motor.  This  deduction  which  is  based  chiefly 
upon  histological  evidence,  has  been  greatly  strengthened  by  Gushing/ 
who,  for  reasons  of  diagnosis,  resorted  to  the  stimulation  of  the  centro- 
parietal  region  in  two  conscious  patients.  The  positive  statement  is 
made  that  distinct  sensations  of  num])ness  and  touch  were  aroused 
which  persisted  as  long  as  the  stimulation  remained  confined  to  the 
post-Rolandic  area.     This  evidence  is  in  agreement  with  the  distri- 


Cefitrcd  Sulcus 


Nucleus  of  funiculi's 
qracilis  ^futi.cunealiis 


Fig.  345. — Schema  Representing  the  Origin  and  Course  of  the  Fibers  of  the  Median 
Fillet — the  Intercentr,^ l  Paths  of  the  Fibers  of  Body  Sense.     {Howell.) 


bution  of  the  afferent  paths  of  the  spinal  cord  and  principally  of  those 
fibers  which  form  its  posterior  funiculi.  We  know  that  the  impulses 
arriving  in  the  nuclei  of  these  tracts,  are  transferred  to  secondary 
neurons  forming  the  internal  arcuate  bundle,  which  crosses  the  mid- 
line in  front  of  the  decussation  of  the  motor  (pyramidal)  tracts.  This 
fact  is  important,  because  it  explains  the  contralateral  character  of 
defects  in  these  sensations.  Beyond  their  decussation  the  sensory 
1  Amer.  Jour,  of  Physiol.,  xxiii,  1909. 


684  THE    CEREBRUM 

fibers  form  a  longitudinal  l^undle  which  is  designated  as  the  median 
fillet  or  lemniscus.  They  terminate  chiefly  in  the  thalamus  superior 
colliculus  of  the  corpora  quadrigemina,  receiving  in  their  course  nu- 
merous fibers  from  the  sensory  nuclei  of  the  cranial  nerves  of  the  oppo- 
site side.  The. thalamus  is  connected  by  tertiary  neurons  with  the 
parietal  region  of  the  cerebrum.  This  explains  the  observation  of 
Campbell,^  that  the  degenerative  changes  associated  with  tabes  dor- 
salis,  finally  progress  into  these  central  paths  and  also  affect  the  cells 
of  the  post-Rolandic  region. 

Regarding  the  character  of  the  sensations  mediated  by  this  area, 
it  has  been  stated  by  Luciani  and  Seppilli  that  they  subserve  the 
muscle  and  cutaneous  senses.  But  as  pain  is  not  felt  as  a  result  of 
the  stimulation  of  this  area,  it  may  be  said  that  it  is  chiefly  concerned 
with  muscular  and  tactile  sensibiHty,  and  in  a  lesser  degree  also  with 
the  temperature  sense.  The  fact  that  the  perceptions  and  judgments 
based  upon  these  sensations  are  mediated  in  the  association  realm  of 
this  region,  is  especially  well  betrayed  bj'  the  diminution  and  loss  of 
the  stereoscopic  acuity  (astereognosis)  invariably  following  lesions  of 
this  area.  In  other  words,  defects  of  the  post-Rolandic  region  give 
rise  to  a  more  or  less  imperfect  judgment  of  the  shape  and  texture  of 
objects  when  handled.  Doubtlessly,  therefore,  this  psychical  difficulty 
must  be  dependent  upon  a  loss  of  those  associations  which  are  ordina- 
rily obtained  with  the  help  of  the  cellular  units  of  this  area.  Another 
psychic  defect  frequently  associated  with  injuries  to  this  region,  is 
tactile  agnosia,  i.e.,  an  inability  to  form  judgments  regarding  the 
ordinary  sensations  of  touch. 

THE  PSYCHO -VISUAL  REGION 

The  Visual  Center. — The  fact  that  vision  is  under  the  control  of 
a  definite  region  of  the  cerebral  cortex  was  discovered  by  Panizza  in 
1855.  It  was  found  that  an  injury  to  one  posterior  tip  of  the  cerebrum 
of  the  dog  gives  rise  to  blindness  in  the  opposite  eye.  This  same  obser- 
vation was  made  subsequently  by  Hitzig  (1874),  but  without  knowing 
that  it  had  already  been  called  attention  to  previously.  It  was  left 
to  Munk  (1878)  to  prove  that  the  destruction  of  certain  parts  of  the 
occipital  lobes  leads  to  total  psychical  or  cortical  blindness.  These 
terms  were  used  to  indicate  that  the  loss  of  vision  is  not  due  in  this 
particular  case  to  a  functional  uselessness  of  the  retina  or  of  the  re- 
fracting media  of  the  eyes,  but  to  a  central  defect  involving  the 
perceptions  and  judgments  pertaining  to  visual  sensations.  Omitting 
the  controversial  discussions  arising  in  consequence  of  this  discovery 
which  were  participated  in  by  Goltz  and  Luciani,  it  may  be  stated 
in  brief  that  the  more  recent  experiments  have  fully  substantiated 
these  results  of  Munk.^     Thus,  Schaeffer  (1888),  Brown  (1890),  and 

1  Histol.  Studies  on  Localization  of  Cerebral  Functions,  Cambridge,  1905. 

2  tjber  die  Funkt.  der  Grosshirnrinde,  Berlin,  1890,  and  Berliner  Akad.  der 
Wissenschaften,  1892-1901. 


CEREBRAL    LOCALIZATION  685 

others,  have  shown  that  in  the  monkeys  the  ablation  of  the  occipital 
lobes  produces  a  permanent  and  total  blindness.  This  result  has 
also  been  obtained  by  Panichi  (1895),  with  this  difference,  however, 
that  the  blindness  can  only  be  made  permanent  by  extending  the 
ablation  somewhat  beyond  the  commonly  accepted  boundaries  of  the 
occipital  lobes. 

With  the  exception  of  certain  minor  details,  the  visual  center  may, 
therefore,  be  said  to  be  situated  in  the  occipital  realm  of  the  cerebrum, 
and  this  conclusion  is  well  borne  out  by  the  defects  following  the 
extirpation  of  only  one  of  these  lobes.  Under  this  condition  we  obtain 
a  blindness  w'hich  is  confined  to  the  corresponding  halves  of  the  retinae, 
in  other  words,  a  bilateral  hemianopia.  The  term  of  hemianopsia 
may  also  be  used  to  indicate  this  condition,  because  it  refers  to  a  loss 
of  vision  in  one-half  of  each  visual  field,  while  the  former  more  directly 
applies  to  a  loss  of  function  of  one-half  of  each  retina. 

The  results  of  this  operation,  however,  differ  somewhat  in  different 
animals,  but  this  should  not  surprise  us,  because  attention  has  already 
been  called  to  the  fact  that  the  fibers  emerging  through  the  optic 
nerve,  do  not  pursue  a  uniform  course.  We  have  seen  that  they 
cross  the  mid-line  completely  in  some  animals  and  only  partially  in 
others.  In  the  first  instance,  the  ablation  of  the  occipital  cortex  of 
one  side  must,  of  course,  lead  to  a  total  blindness  in  the  opposite  eye. 
It  seems  advisable,  however,  not  to  extend  this  discussion  unduly, 
but  to  confine  ourselves  to  the  conditions  met  with  in  man.  We  find 
here  that  the  destruction  of  one  occipital  lobe  is  followed  by  disturb- 
ances in  vision  of  hemiopic  character,  i.e.,  by  a  bilateral  homonymous 
hemianopsia.  Thus,  an  injury  to  the  left  center  produces  a  blindness 
in  the  outer  half  of  the  left  and  the  inner  haK  of  the  right  eye,  and  a 
loss  of  vision  iQ  the  opposite  half  of  the  visual  field  of  each  eye. 
Quite  similarly,  a  lesion  affecting  the  right  center  causes  bhndness  in 
the  two  right  halves  of  the  retinae  and  left  halves  of  the  visual  fields. 
This  implies  that  the  crossing  of  the  retinal  fibers  is  about  equal.  It 
is  to  be  emphasized,  however,  that  the  foveae  centrales  are  not  involved, 
and  hence,  the  field  of  direct  and  most  acute  vision  is  always  excepted 
(Fig.  319).  This  peculiarity  is  explained  by  saying  that  the  fovea  cen- 
tralis of  each  eye  is  connected  with  both  centers,  i.e.,  the  foveae  are 
bilaterally  represented.^ 

Very  pecuUar  types  of  bhndness  result  if  the  lesion  is  situated  in  the 
course  of  the  fibers  connecting  the  retinae  with  the  cortical  center  for 
vision.  Thus,  it  must  be  evident  that  the  destruction  of  one  optic 
nerve  must  lead  to  a  total  blindness  in  the  corresponding  eye,  while  a 
lesion  situated  in  the  chiasma  must  produce  bilateral  defects  in  ac- 
cordance with  its  location  and  extent.  In  a  similar  way,  it  may  be 
inferred  that  the  destruction  of  the  central  optic  tract  posterior  to 
the  chiasma  must  give  rise  to  a  hemianopia  in  the  corresponding  halves 

^  Sachs,  Der  Hinterhauptlappen,  Leipzig,  1892;  also:  Laqueur  and  Schmidt, 
Virchow's  Archiv,  clviii,  1900,  466. 


686  THE    CEREBRUM 

of  the  retinae.  In  many  of  these  cases,  however,  a  tertiary  type  of 
degeneration  frequently  results  which  involves  certain  neurons  which 
are  not  directly  affected  by  the  primary  lesion.  This  spreading 
gives  rise  to  "syinpathetic"  effects,  so  that  bilateral  defects  in  vision 
may  be  obtained  in  spite  of  the  fact  that  the  original  injury  is  con- 
fined to,  say,  one  of  the  optic  nerves  and  should,  therefore,  have  pro- 
duced bhndness  in  only  the  corresponding  eye. 

Visual  Association. — Upon  genetic  grounds  it  must  be  granted  that 
the  optic  nerves  are  really  not  peripheral  nerves  at  all,  but  true  cerebral 
tracts,  bearing  a  close  resemblance  to  the  lemniscus  and  other  systems.  ^ 
Hence,  the  retina  must  be  regarded  merely  as  an  exposed  feeler  of  the 
nervous  system  which  is  excited  by  the  ethereal  rays  of  light  entering 
its  substance.  The  impulses  here  generated  are  transferred  to  central 
parts  over  neurons,  the  cell-bodies  of  which  are  situated  in  the  retinae. 
It  is  true,  however,  that  the  optic  nerves  also  embrace  a  small  number 
of  centrifugal  conductors  which  end  in  arborizations  around  certain 
elements  of  the  retinae.  The  function  of  these  fibers  is  not  known. 
We  have  previously  seen  that  the  centripetal  fibers  of  this  tract  con- 
nect with  the  superior  colliculus,  lateral  geniculate,  and  thalamic 
nuclei,  and  that  the  psychovisual  centers  in  the  occipital  realms  of 
the  cerebrum  are  more  directly  reached  by  way  of  the  thalamo- 
geniculate bodies  and  the  occipitothalamic  radiations.  In  the  course 
of  the  development  of  this  cortical  area,  the  importance  of  the  lower 
visual  centers  formed  by  the  aforesaid  masses  of  gray  matter,  dimin- 
ishes gradually.  In  the  higher  animals,  the  latter  retain  merely  the 
function  of  ordinary  relay  stations  for  reflex  action,  while  visual  per- 
ception and  memory  are  concentrated  in  the  cortical  area.  In  the 
simpler  forms,  such  as  the  fish,  these  lower  centers  form  the  terminal 
stations  of  the  optic  tract  and  must,  therefore,  be  capable  to  mediate 
in  addition  the  psychical  processes  connected  with  vision.-  It  may 
be  concluded,  however,  that  the  psychical  activity  of  these  animals 
is  at  best  extremely  rudimentary. 

The  psycho-visual  area  is  composed  of  two  fields,  one  being  re- 
stricted to  visual  perception  and  the  other  to  visual  memory.  Having 
reached  the  visual  sphere,  the  retinal  impulses  are  transferred  to  con- 
sciousness as  perceptions  which  are  then  relegated  to  the  memor}^  field 
by  way  of  association  fibers.  Stress  has  been  placed  upon  the  fact  that 
the  visual  center  cannot  be  restricted  to  a  narrow  sphere,  although 
Henschen^  has  stated  that  the  visual  paths  of  man  terminate  around 
the  calcarine  fissure  on  the  mesial  surface  of  the  cerebrum.  In  support 
of  this  contention  it  has  been  mentioned  that  the  examination  of  the 
brain  of  Laura  Bridgman,^  the  blind  deaf-mute,  has  shown  decided 

1  Parker,  Am.  Nat.,  xlu,  1908,  601. 

-  Harris,  Brain,  xxvii,  1904,  106 ;  also :  Vincent,  Jour.  Animal  Behavior,  ii, 
1912,  249. 

3  Brain,  xvi,  1893,  170. 

^  Donaldson,  Am.  Jour,  of  Psychol.,  1892,  4. 


CEREBRAL    LOCALIZATION  087 

atrophic  changes  in  the  region  of  the  ciincus,  which  is  situated  above 
this  fissure. 

In  addition,  Flcchsig*  has  proved  by  means  of  the  myehnization 
method  that  the  optic  fibers  terminate  largely  in  the  region  situated 
along  the  calcarine  fissure,  i.e.,  in  the  cuneus  as  well  as  in  the  gyrus 
lingualis.  The  same  inference  may  be  drawn  from  the  clinical  data 
compiled  by  Crispolti  (1902),  which  show  that  the  most  permanent 
types  of  hemianopia  result  from  lesions  of  this  particular  area. 

The  tendency,  therefore,  is  to  regard  the  cuneus  as  a  more  impor- 
tant area  of  the  visual  center  than  the  lo])ulus  lingualis  and  fusiformis. 
Besides  these  regions,  however,  which  border  upon  the  calcarine  fissure, 
the  psycho-visual  sphere  also  embraces  the  three  occipital  convolutions 
and  even  encroaches  upon  the  outlying  districts  of  the  parietal  and 
temporal  lobes.  Evidently,  the  fields  named  last  are  set  aside  for 
visual  memory.  Any  attempt,  however,  to  localize  these  psychic 
areas  more  sharply  must  meet  with  failure.  Thus,  it  does  not  seem 
correct  to  assume  with  Henschen  and  in  accordance  with  the  theory 
of  IMunk,  that  the  retinal  elements  are  projected  in  the  visual  center 
as  individual  units,  because  we  are  in  no  position  to-day  to  support  a 
contention  of  this  kind  by  facts.  This  projection  would  imply  that 
those  elements  w^hich  are  situated  in  the  upper  area  of  the  retina,  are 
associated  by  the  cellular  units  of  the  cuneus,  while  those  situated 
below  are  associated  by  the  lobulus  lingualis.  The  point  most 
frequently  mentioned  against  such  an  almost  mathematical  subdivi- 
sion of  the  visual  center  into  visual  units  of  definite  value,  is  the  fact 
that  Monakow^  and  Bernheimer^  have  shown  that  the  fibers  innervat- 
ing the  yellow  spot,  are  widely  scattered  through  the  occipital  cortex, 
and  do  not  terminate  in  a  circumscribed  area  of  this  region. 

The  Connection  between  the  Visual  Center  and  Others. —  The 
fact  that  the  stimulation  of  the  occipital  cortex  gives  rise  to  muscular 
movements,  points  toward  the  existence  of  definite  anatomical  con- 
nections between  the  visual  center  and  the  musculomotor  mechanism. 
The  stimulation  of  the  upper  surface  of  the  right  lobe  causes  the  eyes 
to  be  turned  downward  and  toward  the  left,  while  the  excitation 
of  its  posterior  region  produces  a  deviation  of  the  eyes  upward  and  to 
the  left.  Furthermore,  a  purely  lateral  movement  to  the  left  may  be 
evoked  by  stimulation  of  the  mesial  surface.  It  must  be  conceded, 
therefore,  that  the  visual  sensations  are  expressed  in  this  case  in 
accurate  muscular  movements,  and  that  this  end  can  only  be  attained 
by  efferent  impulses  which  traverse  the  occipitothalamic  radiation 
and  eventually  find  their  way  into  the  nuclei  and  distal  ramifications 
of  the  third,  fourth  and  sixth  cranial  nerves.  It  need  scarcely  be 
emphasized  that  connections  of  this  kind  also  exist  between  this  center 
and  other  motor  paths. 

1  Sachs.    Gesellsch.   der   Wissensch.,   1904. 

^Ergebn.  der  Physiol.,  1907. 

^Archiv  fiir  Ophthalm.,  Ivii,    1904,   363. 


688 


THE    CEREBRUM 


Visual  perception  and  memory  pla}'  an  important  part  in  all  our 
reactions.  This  is  well  shown  by  the  fact  that  lesions  of  the  occipital 
region  lead  not  only  to  hemianopia  but  also  to  psychical  or  cortical 
blindness.  The  latter  condition,  however,  is  not  always  complete, 
but  may  vary  between  a  slight  disturbance  of  our  associations  per- 
taining to  a  certain  number  of  visual  sensations,  and  an  absolute 
inabihty  on  our  part  properly  to  recognize  and  rate  all  our  visual  impres- 
sions. In  some  animals,  for  example,  certain  lesions  may  be  produced 
which  permit  sensations  of  sight  as  such  to  continue,  while  their  ability 
to  recognize  and  properly  associate  these  impressions  is  lost  absolutely. 
This  constitutes  true  psychic  bUndness. 

In  man,  this  condition  which  is  known  as  word-blindness,  was 
first  recognized  in  1877  by  Kussmaul.^  It  is  characterized  by  an 
inability  to  comprehend  printed  or  written  words,  without,  however, 


Fig.  346. — Lateral  View  of  a  Huiiax  Hemisphere;  Cortical  Area  V,  Damage  to 
Which  Produces  "Mixd-blixdn-ess"  (Word-blixdness)  ;  Cortical  Area  H,  D.am.\ge 
TO  Which  Produces  "  Mlvd-deafxess"  (Word-deafxess)  ;  Cortical  Area  S,  D.anlage 
to  Which  Causes  the  Loss  of  Audible  Speech;  Cortical  Area.  TF,  Da^iage  TO  Which 
.Abolishes  the  Pow-ek  of  Writixg.     (Donaldson.) 

involving  the  faculty  of  expressing  our  thoughts  by  words  or  in  writing. 
A  person  so  afflicted  is  capable  of  seeing  and  even  of  copj'ing  the  letters, 
but  he  has  no  associations  pertaining  to  them.  For  this  reason,  they 
remain  absolutely  meaningless  to  him.  He  is,  therefore,  in  the  same 
position  as  a  person  who  attempts  to  read  a  language  with  which  he  is 
not  familiar,  say  Arabic  or  Chinese.  The  condition  of  word-bhndness 
forces  us  to  assume  that  the  psycho-optical  region  embraces  a  cir- 
cumscribed area  which  is  set  aside  for  the  perception  and  memory  of 
letters.  As  primitive  man,  in  aU  probabiUty,  was  not  in  possession 
of  an  association  zone  of  this  kind,  it  has  been  developed  in  the  course 
of  time.  Its  location  has  not  been  definitely  established  as  yet, 
although  those  cases  of  word-bhndness  which  have  come  to  autopsy, 
have  shown  lesions  in  the  second  parietal  convolution  and  gyrus 
1  Storungen  der  Sprache,    1885. 


CEREBRAL    LOCALIZATION  089 

an<i;ul:iris  of  the  left  side.     This  area  forms  the  outlying  district  of 
the  ineinor}'  realm  of  the  psyeho-visual  region. 

THE  PSYCHO-AUDITORY  REGION 

The  Auditory  Center. — The  first  tangil)le  data  regarding  the  loca- 
tion of  the  au(Htory  center,  have  been  furnished  by  Ferrier  in  1875.  It 
was  found  at  that  time  that  the  excitation  of  the  surface  of  the  temporal 
lobes  gives  rise  to  muscular  movements  involving  the  ear  of  the  oppo- 
site side.  Somewhat  later,  when  these  experiments  were  extended  to 
inchule  ablation  of  this  particular  area  of  the  cerebral  cortex,  it  was 
established  that  the  destruction  of  both  temporal  lobes  produces  total 
deafness,  while  the  ablation  of  only  one  lobe  leads  solely  to  an  impair- 
ment of  hearing.  Subsequent  experimentation  l)y  ]\Iunk  (1878-81), 
Luciani  and  Tamburini  (1879),  and  Bechterew  (1887)  has  proved  this 
localization  to  be  essentially  correct.  In  addition,  it  has  been  pointed 
out  that  the  psycho-acoustic  region  embraces  not  only  the  temporal 
lobe  but  also  the  fields  extending  from  here  in  the  direction  of  the 
parieto-occipital  convolutions  and  the  gyrus  hippocampi. 

These  outlying  districts  appear  to  be  set  aside  for  memory,  while  the 
chief  area  of  this  center  seems  to  be  restricted  to  the  superior  temporal 
convolution.  This  deduction  is  based  upon  the  results  of  stimulation 
of  the  surface  of  the  temporal  cortex  as  well  as  upon  the  manner  of  dis- 
tribution of  the  incoming  fibers,  as  determined  by  the  myelinizat ion- 
method  of  Flechsig.^  It  seems  that  the  fibers  of  the  auditory  radia- 
tion terminate  chiefly  in  the  superior  convolution  of  this  lobe 
(Monakow).      This  area  also  embraces  a  sphere  for  musical  sounds. 

The  experiments  of  unilateral  extirpation  of  the  temporal  lobes 
have  also  brought  out  the  fact  that  the  deafness  resulting  therefrom, 
is  only  temporary,  and  that  the  symptoms  are  chiefly  confined  to  the 
ear  of  the  opposite  side.-  This  result  strongly  suggests  a  crossing  of 
the  auditory  fibers  which,  as  we  have  seen  in  an  earlier  chapter,  takes 
place  in  the  corpus  trapezoideum.  This  decussation  is  incomplete  and 
may,  therefore,  be  likened  to  that  occurring  in  the  optic  chiasma. 
Thus,  it  may  be  gathered  that,  in  the  dog,  the  organ  of  Corti  in  the  coch- 
lea is  bilaterafly  represented.  Besides  this  rather  incomplete  and 
temporary  deafness,  the  destruction  of  the  temporal  cortex  also  gives 
rise  to  psychic  or  cortical  deafness,  which  means  that  the  animal 
hears  the  sounds,  but  is  quite  unable  to  understand  them. 

This  condition  has  also  been  observed  in  persons  who  at  autopsj^ 
showed  characteristic  lesions  of  the  temporal  cortex.  They  appeared 
to  be  able  to  hear  even  whispers,  but  could  not  comprehend  their 
meaning.  In  analogy  to  word-blindness,  Kussmaul  (1876)  designated 
this  condition  later  on  as  word-deafness.  Luciani  and  Seppilh  local- 
ized the  seat  of  this  difficult}'  in  the  first  and  second  temporal  con- 

1  Neurol.  Zentralblatt,  1903,  202. 

-  Tamburini,  Revista  di  Freniatria,  Reggio  Emilia,  1903. 

44 


690  THE    CEREBRUM 

volutions  of  the  left  side.  A  person  so  afflicted  is  in  the  same  position 
as  one  who  is  spoken  to  in  a  foreign  language,  i.e.,  he  hears  the  words, 
but  is  unable  to  depict  their  meaning,  because  he  cannot  properly 
associate  them.  Wernicke^  recognized  at  an  early  date  that  this  con- 
dition, together  with  word-blindness,  must  lead  to  a  loss  of  speech, 
because  individuals  who  thus  fail  in  their  associations,  cannot  react 
to  auditory  and  visual  impressions  by  the  production  of  coordinated 
sounds.  It  may  also  be  inferred  that  they  cannot  react  to  these  im- 
pressions by  the  act  of  writing  for  the  same  reason.  The  latter  condi- 
tion is  known  as  agraphia,  and  the  former  as  aphasia. 

THE  CENTERS  FOR  SMELL  AND  TASTE 

The  Location  of  the  Olfactory  Center. — The  sense  of  smell  is  very 
unequally  developed.  We  have  seen  that  it  forms  the  dominant  sense 
in  many  of  the  lower  vertebrates;  for  example,  in  the  fish  in  which 
almost  the  entire  cerebrum  is  concerned  with  this  function.  These 
animals,  however,  are  not  in  possession  of  a  true  cerebral  cortex,  the 
first  indications  of  it  appearing  in  the  amphibia  and  reptilia.  Other 
animals  are  entirely  lacking  in  olfactory  organs ;  for  example,  the  dol- 
phin, porpoise  and  whale.  ^  This  divergency  enables  us  to  divide 
animals  into  two  groups,  namely  into  osmatic  and  anosmatic,  and  the 
former  again  into  macrosmatic  and  microsmatic.  As  examples  of  the 
first  kind,  might  be  mentioned  the  dog,  rabbit,  rat  and  opossum  and  as 
an  example  of  the  second  kind,  man. 

The  acuity  of  this  sense  is  in  keeping  not  only  with  the  complexity 
of  the  olfactory  cells  in  the  nasal  cavity,  but  also  with  that  of  the 
association  area  in  the  cortex.  In  the  fish,  the  reactions  following 
olfactory  impressions,  are  still  chiefly  reflex.  A  true  cortical  or  psychic 
element  is  first  imparted  to  them  in  the  amphibians  and  reptiles. 
This  statement  implies,  that  beginning  with  these  animals,  the  ol- 
factory reflex  realm  is  gradually  amplified  by  a  cortical  center.  As 
far  as  man  is  concerned,  this  psycho-olfactory  region  has  been  lo- 
calized by  Ferrier  in  the  gyrus  hippocampi,  and  particularly  in  its 
distal  limb,  the  uncus.  This  conclusion  has  been  reached  partly  in 
accordance  with  the  anatomical  data  pertaining  to  the  distribution 
of  the  olfactory  fibers,  and  partly  because  the  stimulation  of  this  area 
in  monkeys  produces  movements  involving  the  muscles  of  the  lips 
and  nostrils  of  the  same  side.  This  effect  is  similar  in  character  to 
that  produced  by  inhaling  an  irritating  vapor.  It  should  be  remem- 
bered, however,  that  reactions  of  the  latter  kind  are  due  chiefly  to 
the  excitation  of  the  receptors  of  the  trigeminus  nerve.  Luciani 
came  to  the  same  conclusions  as  Ferrier,  but  extended  this  area  some- 
what to  include  the  subiculum  cornu  Ammonis.     Bechterew,^  on  the 

^  Der  aphasische  Symptomenkomplex,  Breslau,  1874. 

2  Zwardemaker,  Ergebn.  der  Physiol.,  i,  1902,  and  Herrick,  Evolution  of 
Intelligence  and  its  Organs,  Science,  xxxi,  1910,  7. 

3  Archiv  fur  Physiol.,   1899,  Suppl.,  391. 


CEREBRAL    LOCALIZATION  (391 

other  hand,  believes  that  Animon's  horn  does  not  form  a  part  of  the 
olfactoiy  area. 

The  Center  for  Taste.— The  psychic  area  for  the  sensations  of  taste 
has  not  been  definitely  located  as  yet.  As  the  taste  buds  are  widely 
scattered,  their  excitation  involves  the  seventh  and  ninth  cranial 
nerves;  in  fact,  Wilson^  states  that  a  few  of  these  receptors  are  also 
situated  in  the  mucous  membrane  of  the  larynx  and  epiglottis.  The 
latter  seem  to  be  innervated  by  the  vagus  nerve.  In  the  medulla 
these  afferent  fibers  are  intimately  connected  with  the  motor  mechan- 
ism concerned  in  mastication  and  deglutition,  as  well  as  with  the 
spinal  nuclei.  They  terminate  finally  in  the  gyrus  hippocampi  near 
the  anterior  end  of  the  temporal  lobe.  In  fishes  these  fibers  may  be 
traced  to  the  region  of  the  hypothalamus. 

THE  CENTER  FOR  SPEECH 

The  Speech  Circuit. — The  psychic  area  for  the  associations  required 
in  the  production  of  intelligent  sounds  and  speaking,  should,  of  course, 
not  be  confounded  with  that  region  of  the  cerebral  cortex  which  has  to 
do  with  the  innervation  of  the  muscles  of  the  larynx  and  functionally 
allied  structures  and  forms  a  part  of  the  general  motor  area.  In 
fact,  these  motor  points  are  under  the  direct  control  of  the  psychic 
speech  center.  In  the  latter  area  the  various  revalent  associations 
from  the  visual,  auditory  and  other  centers  are  brought  together  and 
are  psychically  adapted  to  speech.  The  speech  center,  therefore,  is 
the  seat  of  those  memories  which  are  required  for  the  execution  of  the 
perfectly  definite  and  coordinated  movements  necessary  for  speaking. 

Sounds  are  a  common  phenomenon  in  nature.  We  cannot,  how- 
ever, concern  ourselves  at  this  time  with  the  reflex-like  production  of 
noises,  such  as  result  in  insects  in  consequence  of  the  rubbing  together 
of  the  legs  or  mandibles.  The  first  indications  of  true  associated 
sounds  are  present  in  amphibians  and  reptiles,  but  only  in  a  rudimen- 
tary manner,  because  the  cerebral  cortex  of  these  animals  is  largely 
concerned  with  olfaction.  Such  noises,  however,  as  are  produced  by 
means  of  resonating  pouches,  seem  to  contain  at  least  a  slight  cortical 
element.  Somewhat  higher  in  the  scale  of  the  Animal  Kingdom  this 
psychic  admixture  becomes  unmistakable.  Its  increasing  conspicuous- 
ness  pursues  a  course  parallel  to  the  retrogression  of  the  olfactory 
apparatus  and  the  development  of  the  association  areas  pertaining  to 
other  senses.  Undoubtedly,  this  change  is  far  advanced  in  the  birds 
and  is  almost  complete  in  the  monkeys  and  apes.  In  the  mammals, 
the  production  of  sounds  is  universal  and  diversified,  but  the  range  of 
these  sounds  is  relatively  limited.  In  other  words,  the  sounds  which 
they  produce  are  few  in  number,  but  are  nevertheless  made  for  very 
specific  purposes.  In  this  connection,  brief  reference  might  be  made 
to  certain  seemingly  authentic  cases  which  suggest  that  it  is  possible 

1  Brain,  xxviii,  1905,  339. 


692 


THE    CEREBRUM 


to  train  animals  to  produce  a  definite  number  of  associated  sounds. 
Instances  of  this  kind  are  the  "talking  dog"  and  the  "talking  horse." 
The  higher  monkeys,  it  is  said,  are  capable  of  uttering  a  few  coordinated 
sounds  in  expression  of  particular  mental  concepts. 

A  true  coordination  of  sounds  in  the  form  of  speech,  however, 
is  shown  only  by  man.  This  achievement  is  made  possible  very 
largely  by  the  development  of  the  association  area  pertaining  to 
this  function  and  not  by  a  correspondingly^  much  greater  intricacy 
of  the  motor  apparatus  necessary  for  speaking.  Already  dur- 
ing infancy,  man  is  equipped  with  a  phonetic  mechanism  which  is 
practically  complete  as  far  as  its  structural  complexity  is  concerned, 
but  is  still  in  need  of  functional  development.  This  it  acquires 
in  the  course  of  the  succeeding  years.  This 
awakening  of  the  associations  concerned  in  speech, 
is  one  of  the  most  interesting  and  instructive  phe- 
nomena in  the  life  of  man.  The  primary  cooing 
sounds  of  the  infant  are  gradually  amplified  by  a 
number  of  successive  sounds  having  a  definite 
meaning.  This  augmentation  indicates  an  exten- 
sion and  melting  together  of  intracerebral  paths, 
so  that  various  impressions  from  other  association 
centers  may  be  brought  to  bear  upon  speech. 
Once  this  union  has  been  effected,  the  develop- 
ment of  speech  is  much  more  rapid,  being  subject, 
of  course,  to  differences  in  the  training  of  the  child. 
Speaking  is  the  outcome  of  certain  mental  pro- 
cesses; in  other  words,  it  is  the  result  of  particular 
afferent  impulses  which  may  enter  the  body  by 
way  of  practically  any  receptor.  They  are  then 
associated  in  the  perception  and  memor}^  realms 
sociation  center;  C.'cen-  of  the  corresponding  regions  of  the  cerebral  cortex, 
ter  for  speech;  Af,  motor  ^g  speech  follows  visual,  auditory,  tactile  and  other 
larynx-  L^^^lary^!  ^^  °  imprcssious,  it  may  be  said  that  these  mechanisms 
are  really  tributary  to  the  speech  center.  Hence, 
speech  is  the  product  of  a  harmonious  interaction  between  different 
peripheral  and  central  nervous  mechanisms.  It  is  true,  however,  that 
these  tributary  complexes  are  not  developed  simultaneousl}^  but  suc- 
cessively, and  that  training  has  much  to  do  with  their  functional 
adaptability  to  speech.  Thus,  it  is  a  common  experience  that  the 
memory  sphere  of  vision  becomes  functional  at  an  earlier  date  than 
that  of  audition;  at  least,  it  seems  more  difficult  for  the  infant  to 
make  the  latter  subservient  to  its  speech  requirements. 

The  morphological  and  functional  arrangement  of  the  adult 
mechanism  of  speech  may  be  illustrated  best  in  the  form  of  a  diagram. 
It  has  been  said  that  speech  is  under  the  control  of  an  association  area 
situated  in  the  cortex  of  the  cerebrum  (Fig.  347).  This  center  stands 
in  communication  with  the  phonating  organs,  the  larynx  and  alhed 


^ 


y 


FiG.  347. — The  Speech 
Circuit. 
R,  Receptor;  V,  as 


CEREB  KA  L    LOC  A  LI  Z  ATI  ON 


693 


parts  (L),  by  moans  of  an  offcront  path  through  tho  motor  area  (M). 
This  entire  complex,  inchisive,  so  to  speak,  of  one-half  of  the  center  of 
speech,  forms  the  motor  arc  of  the  speech  circuit.  But,  inasmuch  as 
speech  results  only  in  consequence  of  incoming  impulses,  inclusive 
of  those  of  pure  psychic  origin,  this  circuit  can  only  be  completed 
by  bringing  it  into  relation  with  a  sensory  or  afferent  arc.  The  latter 
may  embrace  either  the  visual,  auditory,  or  any  other  mechanism. 
Supposing  that  we  are  now  dealing  with  a  visual  impression,  we  would 
say  that  the  stimuli  are  received  upon  the  retina  (R)  and  are  then 
conveyed  to  the  visual  center  in  the  occipital 
cortex  for  proper  association  (V).  From 
here  they  are  conducted  to  the  center  of 
speech  by  way  of  definite  association  fibers. 
In  the  chief  center  they  are  then  remodelled 
and  transferred  upon  the  efferent  path  by 
way  of  which  they  attain  the  larynx.  Natur-  ' 
ally,  if  speech  is  the  outcome  of  an  auditory 
impression,  the  organ  of  Corti  and  the  audi- 
tory center  would  have  to  be  substituted  for 
the  retina  and  the  visual  center,  but  the 
motor  path  remains  the  same. 

The  Location  of  the  Center  for  Speech. 
Aphasia. — Adult  persons  are  capable  of  com- 
municating their  mental  products  to  one 
another  by  means  of  mimic  movements, 
speech  and  writing.  The  second  of  these 
means  has  been  shown  by  Broca^  to  be  lost 
whenever  the  base  of  the  left  inferior  frontal 
convolution  is  extensively  injured.     For  this 

reason,  this  investigator  recognized  in  this  Fig.  348.— Dl\gr.\m  of  the 
area  the  cortical  regulatory  factor  of  speech,  Speech  Cikcuit,  Illustr.\tixg 

or  more  correctly  speaking,  of  the  motor  ap-   ^  Position  of  the  Lesions 
,  .   ,      ,      ■  .        .  .  »  \Nhich  Give  Rise  to  Sensory 

paratus  which  derives  its  innervation  Irom  and  Motor  Aph.^sia. 

the  fifth,  seventh  and  ninth  to  twelfth  cranial        r,  Receptor;  V,  association 

nerves.     He  designated  the  aforesaid  condi-  center;  c,  speech  center;  M, 

,.      ,  ,  1        •        ii  1        r  motor   points;  L,  larynx;  5^, 

tlOn    as    cortical  motor  aphasia,  thereby  fur-    realm  of  sensory  aphasia;  MA. 

nishing  the  basis  for  the  commonly  accepted  realm  of  motor  aphasia. 
view  that  the  speech  center  is  situated  in  the 

left  inferior  frontal  convolution.  We  shall  see  later  on  that  this  locali- 
zation is  not  quite  correct,  because  it  is  restricted  to  too  narrow  a 
sphere.  In  this  connection  attention  should  also  be  called  to  the  fact 
that  cerebral  localization  should  never  be  attempted  upon  a  strictly 
anatomical  basis.     Function  should  really  be  the  deciding  factor. 

The  term  aphasia  signifies  a  loss  of  the  power  of  speech  (Fig .  348) .    An 
individual  so  afflicted  is  unable  to  express  his  ideas  in  spoken  words. 
The  difficulty,  however,  does  not  he  in  the  larynx  nor  in  the  paths  con- 
^  In  amplifiration  of  the  observation  of  Bouillaud,  1825. 


A* 


694  THE    CEREBRUM 

necting  this  organ  with  the  cerebrum.  This  is  shown  by  the  fact  that 
its  movements  dm^ing  respiration,  mastication  and  deglutition  are 
executed  with  perfect  precision,  and  may  even  be  used  for  mimic  ex- 
pressions, singing  and  whistling.  Aphasia,  therefore,  is  an  intracere- 
bral defect  involving  the  spontaneity  or  power  of  phonetic  expression 
(Fig.  348).  This  implies  that  the  aphasic  person  is  no  longer  in  a 
condition  to  express  his  thoughts  in  words  which  form  his  principal 
means  of  communication  with  his  fellow-men.  To  be  sure,  man  is 
also  subject  to  a  number  of  conditions  in  which  the  intellectual  facul- 
ties are  in  abe3'ance,  either  from  birth,  as  in  idiots,  or  from  disease,  as 
in  coma,  stupor,  dementia  and  certain  states  of  hysteria.  This  type  of 
speechlessness,  although  due  to  cerebral  defects,  cannot  be  classified 
as  aphasia. 

Motor  aphasia  is  the  result  of  an  injury  either  to  the  efferent  or  motor 
realm  of  the  speech  center  or  to  the  path  connecting  it  with  the  motor 
area  situated  along  the  fissure  of  Rolando,  The  motor  area  itself, 
however,  is  not  affected  in  cases  of  pure  aphasia,  as  is  evinced  by  the 
fact  that  the  muscles  used  in  speaking  are  not  paralyzed  but  have  only 
lost  their  central  directing  influence.  For  this  reason,  we  must  think 
of  the  motor  realm  of  the  center  of  speech  as  a  storehouse  of  those 
memories  which  are  directly  concerned  with  articulation  and  the 
phonetic  construction  of  words.  To  be  sure,  an  injury  may  be  so 
extensive  that  it  also  involves  the  motor  area,  in  which  case  the  aphasia 
is  associated  with  a  hemiplegia.     This  is  not  at  all  uncommon. 

It  is  possible  to  amplify  these  associations  and  to  impart  to  them 
a  specificity  which  in  turn  will  tend  to  render  the  action  of  the  laryn- 
geal parts  more  and  more  effective.  In  other  words,  while  the  laryn- 
geal parts  may  be  fully  developed,  they  cannot  attain  their  greatest 
functional  efficiency  unless  the  association  realm  is  trained  and  made 
to  progress  in  a  corresponding  measure. 

An  injury  to  this  center  most  frequently  results  in  consequence  of 
traumas  and  hemorrhages  in  the  region  of  the  middle  cerebral  artery. 
These  lesions  may  be  very  extensive  or  more  or  less  restricted;  hence, 
the  resulting  motor  aphasia  or  aphemia  may  be  either  complete  or  partial 
in  character.  In  the  former  case,  the  person  loses  his  power  of  speech 
absolutely,  while  in  the  latter  he  retains  the  faculty  of  uttering  a  limited 
number  of  words.  Thus,  Broca  has  described  a  person  suffering  from 
a  loss  of  all  numerical  concepts  with  the  exception  of  the  term  "three," 
this  number  being  employed  by  him  constantly  in  referring  to  all  nu- 
merical values.  Quite  similarly,  a  person  may  lose  the  use  of  certain 
nouns  and  pronouns,  or  persistently  employ  words  in  wrong  combina- 
tions (paraphasia).  The  point  to  be  emphasized  is  that  these  defects 
in  speech  may  be  so  specific  that  they  may  almost  be  compared  to  the 
loss  of  one  of  the  strings  of  a  piano  or  other  musical  instrument. 

Another  point  to  be  noted  is  that  the  mental  faculties  of  a  person 
afflicted  with  motor  aphasia,  are  generally  preserved,  provided,  of 
course,  that  the  injury  is  perfectly  localized.     This  impHes  that  his 


CEREBRAL    LOCALIZATION  695 

power  of  assooiiit  iug  tlio  various  sensory  impressions  is  relatively  normal, 
although  he  absolutely  fails  in  his  attempts  to  give  verbal  expression  to 
these  concepts.  Indeed,  a  person  of  this  kind  may  be  told  the  missing 
words  repeatedly  without  being  a])le  to  utter  them,  for  the  reason  that 
his  power  of  forming  words  has  been  lost.  It  is  true,  however,  that 
any  statement  which  definitely  asserts  that  there  is  no  impairment  of 
the  intellectual  faculties  in  motor  aphasia,  should  be  accepted  with 
reserve,  because  aphasias  unaccompanied  by  a  lowering  of  other 
faculties  are  not  common.  A  pure  motor  aphasia  is  designated  as 
aphemia.  The  real  determining  factor  of  the  loss  of  intelligence, 
associated  with  aphasia,  is  the  cause  and  extent  of  the  lesion,  because  it 
is  more  than  probable  that  a  degenerative  process  affecting  the  frontal 
convolutions,  most  generally  passes  beyond  the  confines  of  this  region 
and  also  involves  more  distant  areas  of  the  cerebrum.  Thus,  while 
these  patients  may  deport  themselves  reasonably  well  and  even  con- 
tinue to  transact  ordinary  business,  their  difficulty  in  speech  is  in 
many  cases  associated  with  others,  such  as  an  at  least  partial  paralysis  ^ 
of  the  skeletal  muscles,  showing  an  involvement  of  the  motor  area 
(hemiplegia),  or  an  anarthria,  proving  an  impairment  of  the  motor 
power  of  expression  (Marie).  The  latter  condition  usually  indicates  a 
lesion  of  the  white  matter  of  the  external  capsule  as  its  winds  around 
the  lenticular  nucleus. 

In  many  cases  of  aphasia,  we  also  observe  a  loss  of  the  power  of 
writing  (agraphia),  or  a  loss  of  the  power  of  making  purposive  move- 
ments of  a  familiar  kind  (apraxia).  The  latter  condition  may  be 
tested  by  handing  the  patient  a  comb,  drinking  glass,  matches,  or  other 
articles  and  noticing  whether  he  knows  how  to  use  them.  Apraxia 
may  be  sensory  or  motor  in  its  character. 

This  discussion  inadvertently  leads  us  to  the  further  consideration 
of  the  data  supplied  by  Bouillaud  and  Broca  in  support  of  the  contention 
that  the  speech  center  is  located  in  the  left  inferior  frontal  convolution. 
It  has  been  stated  that  this  is  true  only  in  right-handed  persons,  i.e.,  in 
about  95  per  cent,  of  people,  and  that  this  center  is  situated  on  the  right 
side  in  left-handed  individuals  (Noison,  1862).  Moreover,  it  is  a 
common  experience  that  reeducation  is  difficult  to  accomplish  in  the 
adult,  but  not  in  children.^  This  fact  seems^to  suggest  that  the  destruc- 
tion of  the  aforesaid  area  in  children,  allows  the  elements  in  the  opposite 
frontal  lobe  to  develop  into  a  true  center.  Very  difficult  to  understand 
are  those  cases  which  prove  that  aphasia  may  be  present  in  an  individual 
whose  inferior  frontal  lobe  was  shown  at  necropsy  to  be  free  from 
lesions.  Again,  it  has  been  demonstrated  that  aphasia  may  be  absent  in 
cases  of  undisputed  destruction  of  Broca's  area.^  Montier  presents  the 
records  of  108  trustworthy  cases.  Of  these,  19  support  Broca's  conten- 
tion, while  84  are  against  it.  In  57  of  them  motor  aphasia  was  present 
in  spite  of  the  fact  that  Broca's  area  was  intact,  while  the  others  showed 

1  Gowers,  Diseases  of  the  Brain,  London,  1885. 

^  Monakow,  Gehirnpathologie,  1906,  and  Collier,  Brain,  1908. 


696  THE    CEREBRUM 

a  destruction  of  this  region,  but  no  aphasia.  It  seems,  therefore,  that 
we  cannot  adhere  to  the  old  view  of  Broca,  but  must  regard  this 
particular  area  merely  as  a  link  in  the  chain  of  tha  speech  circuit.  As 
speech  is  a  skilled  act,  involving  several  cerebral  regions,  Marie ^ 
believes  that  it  cannot  be  referred  to  any  particular  group  of  cells  to 
the  exclusion  of  another.  The  latter  point  will  be  brought  out  more 
clearly  during  the  succeeding  discussion  upon  sensory  aphasia. ^ 

Sensory  Aphasia. — Speaking,  as  well  as  writing,  necessitates  the 
presence  of  distinct  concepts  which  may  be  memories  of  visual  sensa- 
tions, auditory  sensations,  tactile  sensations  and  others.  Hence, 
it  may  be  gathered  that  speech  must  be  lost  whenever  these  associa- 
tions are  absent,  because  it  then  lacks  its  causative  factors.  In  other 
words,  a  person  may  be  in  complete  possession  of  the  power  of  articu- 
lation and  phonation,  but  be  quite  unal^le  properly  to  construct  those 
mental  pictures  or  concepts  which  ordinarily  give  rise  to  speech. 
In  this  case,  therefore,  the  difficulty  lies  on  the  sensory  side  of  the  speech 
circuit. 

We  have  previously  seen  that  an  injury  to  Wernicke's  area  of  the 
temporal  lobe  gives  rise  to  word-deafness,  i.e.,  to  an  inability  of  cor- 
rectly associating  sounds  or  words,  in  spite  of  the  fact  that  they  are 
clearly  heard.  In  the  same  way,  a  lesion  to  the  parietal  realm  of  the 
psycho-visual  field  may  give  rise  to  the  condition  of  word-blindness, 
i.e.,  to  an  inability  of  associating  written  or  printed  language.  In 
both  cases,  of  course,  the  peripheral  afferent  paths  are  in  perfect  condition, 
and  hence,  the  difficulty  must  be  situated  in  the  auditory  and  visual 
centers.  Under  ordinary  conditions,  these  two  centers  are  the  chief 
contributors  to  the  speech  center  proper,  but  not  in  an  equal  measure, 
because  the  auditory  realm  is  no  doubt  more  directly  associated  with 
it  than  the  visual.  This  is  shown  especially  by  the  fact  that  a  loss  of 
speech  is  more  frequently  associated  with  word-deafness  than  with 
word-blindness.  This  constitutes  the  so-called  sensory  aphasia  of 
Wernicke,^  so  designated  to  differentiate  it  from  the  motor  aphasia 
of  Broca.  A  simple  word-blindness,  on  the  other  hand,  rarely  leads 
to  sensory  aphasia,  but  presents  itself  rather  as  an  inability  to  read 
(alexia)  and  an  inability  to  write  from  copy  (agraphia).  It  may 
happen,  however,  that  the  primary  lesion  does  not  remain  confined 
to  the  psycho-optic  realm  but  also  involves  the  psycho-auditory  field, 
in  which  case,  of  course,  the  aphasia  is  associated  with  both  conditions, 
word-deafness  and  word-blindness,  as  well  as  with  alexia  and  agraphia. 
It  should  also  be  added  that  auditory  aphasia  is  often  combined  with 
at  least  shght  defects  in  hearing,  and  visual  aphasia,  with  certain 
defects  in  sight  (hemianopia).  This  cannot  surprise  us,  because  the 
lesions  involving  these  areas,  are  rarely  so  precisely  placed  as  not  to 
affect  neighboring  units. 

1  Semaine  mcdicale,  Nos.  21,  42  and  48,  1906. 

2  A.  Meyer,  Harv^ey  Lectures,  New  York,  1910,  228. 
'  Der  aphasische  Symptomenkomplex,  Breslau,  1874. 


CEREBRAL    LOCALIZATION 


697 


Strictly  speaking,  however,  the  condition  of  sensory  aphasia 
must  result  in  consequence;  of  any  lesion  producing  a  loss  of  the  intel- 
lectual recognition  of  external  objects  through  any  one  of  our  senses, 
at  least,  of  those  which  ordinarily  give  rise  to  concepts  employed  in 
speech.  On  this  account,  the  different  association  centers  may  really 
be  regarded  as  subsidiary  or  tributary  centers  to  the  speech  center. 
This  failure  of  intellectual  recognition  has  been  designated  as  agnosia; 
hence,  word-deafness  is  really  auditory  agnosia,  and  word-blindness, 
visual  agnosia,  while  stereognosis  is  tactile  agnosia.  Thus,  practically 
any  agnosia  may  give  rise  to  defects  in  expressing  our  ideas  in  words 
or  deeds.  The  location  and  extent  of  these  sensory  lesions  determine 
the  intensity  of  the  aphasia  or  agraphia ;  and  hence,  these  conditions 


Fig.  349. — The  Speech  Circuit  Projected  to  Show  the  Location  of  Lesions  Which 
May  Give  Rise  to  Aphasia. 
E,  Eye;  V,  visual  association  area;  SC,  speech  center;  M,  motor  points;  L,  larynx. 
Sensory  aphasia  follows  injuries  to  the  association  center  {A)  its  transcortical  connecting 
path  {B)  or  the  receiving  side  of  the  center  for  speech  (C).  Motor  aphasia  may  be 
produced  by  an  injury  to  the  motor  neurones  of  the  center  for  speech  {D)  or  its  con- 
necting path  (^E)  with  the  motor  area. 

may  be  either  complete  or  incomplete.  At  all  events,  sensory  apha- 
sics  suffer  in  most  instances  a  greater  deterioration  of  their  mental 
faculties  than  the  simple  motor  aphasics,  because  their  primary  as- 
sociation spheres  are  more  directly  involved.  For  the  present,  there- 
fore, we  must  adhere  to  the  belief  that  the  speech  circuit  consists  of 
a  number  of  distinct  centers,  the  several  activities  of  which  are  com- 
bined into  the  single  product  of  speech.  This  circuit  may  be  broken 
at  different  points,  namely,  at  (a)  the  tributary  association  center,  {h) 
the  association  path  connecting  this  lower  center  with  the  chief  center, 
(c)  the  chief  center  on  its  ingoing  or  sensory  side,  (d)  the  chief  center 
on  its  outgoing  or  efferent  side,  and  (e)  the  association  path  connecting 
the  latter  with  the  motor  area.  Injuries  at  points  a,  h,  and  c,  must 
give  rise  to  sensory  aphasia  and  injuries  at  points  d  and  e,  to  motor 
aphasia. 


698  THE    CEREBRUM 

Agraphia. — As  a  second  means  of  communicating  our  ideas  to  our 
fellow-men,  we  employ  a  code  of  written  signals  which  are  in  no  way- 
less  arbitraiy  than  those  of  speech.  They  differ  with  the  character 
of  the  language  and  hence,  also  with  the  intelligence  of  the  people 
employing  them.  Like  speech,  writing  is  a  skillful  act  and  is  controlled 
by  a  number  of  cortical  centers.  Both  faculties  are  acquired  and  may 
be  perfected  by  training.  First  of  all,  we  observe  that  the  muscles  of 
the  hand  and  fingers  are  controlled  by  certain  units  of  the  motor  area. 
These  in  turn  are  under  the  guidance  of  a  psychomotor  area  of  the 
cortex  which,  as  far  as  is  known,  occupies  a  position  in  or  very  near  to 
the  psychomotor  center  for  speech.  Secondly,  as  writing  is  the  direct 
outcome  of  associative  processes  in  different  sensory  regions  of  the 
cortex,  the  latter  may  be  regarded  as  tributary  areas  to  the  chief  psy- 
chomotor center. 

Theoretically  considered,  therefore,  we  might  recognize  the  exist- 
ence of  a  distinct  writing-circuit,  similar  in  its  outUne  to  the  speech 
circuit.  In  strict  analogy  to  the  latter,  it  might  be  said  to  possess 
a  sensory  and  a  motor  side,  the  ingoing  impulses  being  derived  chiefly 
from  the  visual  and  auditory  centers.  While  this  conception  is  un- 
doubtedly correct  physiologically,  no  pathological  cases  have  been 
recorded  as  yet  which  might  prove  the  power  of  writing  to  be  a  separate 
cortical  entity.  In  fact,  the  records  show  that  agraphia  or  loss  of  the 
power  of  writing,  is  present  only  in  connection  with  at  least  a  slight 
degree  of  aphasia.  This  is  also  true  of  paragraphia,  i.e.,  the  writing 
of  wrong  words,  syllables  and  letters.  Agraphia,  however,  is  due  to  a 
lesion  of  those  psychic  centers  which  are  directly  concerned  with  the  act 
of  writing.  Hence,  writer's  cramp  is  not  an  agraphia,  but  is  due  in  all 
probability  to  a  neurosis  of  psychogenic  origin.  Thus,  this  condition 
is  comparable  to  those  disturbances  in  speech  which  are  classified 
as  stuttering  and  stammering.  Very  characteristic  defects  in  writing 
are  exhibited  in  different  psychoses.  The  paralytic  writes  carelessly, 
leaving  out  words  and  syllables,  while  the  maniac  writes  very  hastily 
and  the  katatonic  in  a  peculiar  stilted  manner.  It  may  be  concluded, 
therefore,  that  speech  and  writing  are  closely  related,  acquired  and 
educative  faculties.  Their  motor  centers,  paths  and  end-organs  are 
quite  distinct,  but  on  the  sensory  side  we  find  that  practically  the  same 
psychic  areas  are  involved  in  the  two  processes.  This  fact  accounts 
for  the  close  relationship  existing  between  agraphia  and  aphasia. 

It  has  also  been  claimed  by  Kussmaul  that  our  musical  faculties 
are  separately  represented  in  the  cerebral  cortex.  This  imphes  that 
the  psycho-visual  and  psycho-auditory  regions  embrace  a  circumscribed 
area  in  which  musical  symbols  and  sounds  are  associated.  This  con- 
clusion is  based  upon  the  fact  that  the  power  of  reading  musical  notes 
may  be  preserved  in  alexia.^  A  condition  of  amusia,  however,  has 
been  repeatedly  observed  in  consequence  of  cerebral  lesions. 

^  Oppenheim,  Charite  Ann.,  1888,  345. 


CEREBRAL    LOCALIZATION  699 

THE  FRONTAL  ASSOCIATION  AREA 

The  preceding  localization  of  the  different  motor  and  sensory  areas 
has  undoubtedly  led  us  to  believe  that  the  cerebral  cortex  embraces 
a  number  of  island-like  fields  which  are  concerned  with  particular 
functions.  While  this  conception  is  correct,  it  should  not  be  forgotten 
that  still  larger  areas  are  situated  in  ])etween  those  already  explored, 
which  have  not  as  yet  been  shown  to  possess  a  specific  functional 
value.  Guided  very  largely  by  the  fact  that  the  aphasics  may  lose 
their  power  of  word-formation  without  suffering  a  decided  impair- 
ment of  their  intelligence,  the  clinicians  have  assumed  that  thought 
is  quite  independent  of  auditory,  visual  and  other  impressions  and 
memories.  In  accordance  with  this  assumption,  it  was  then  believed 
that  the  psycho-optic,  the  psycho-acoustic,  and  other  psychic  areas  are 
apportioned  severally  to  the  different  sense  organs,  and  are  amplified  by 
definite  areas  in  which  solely  the  more  general  psychic  activities  are 
situated. 

This  at  first  purely  hypothetical  center  of  thought  received  a  firmer 
morphological  basis  by  the  investigations  of  Flechsig^  pertaining  to  the 
time  of  myelinization  of  the  fibers  of  the  embryonal  brain.  It  is 
conceivable  that  those  association  areas  of  the  cortex  attain  their 
function  first  which  are  first  placed  in  possession  of  myelinated  fibers, 
and  thus  antecede  the  others  in  gaining  connection  with  the  outgoing 
paths  of  the  white  matter.  By  this  method  Flechsig  succeeded  in 
outlining  thirty-six  different  cortical  fields  which  he  further  divided 
into  'primary,  intermediary  and  terminal.  The  first  attain  their  myelin- 
ated fibers  at  birth  and  constitute  the  primary  sense  centers,  namely, 
those  of  smell,  cutaneous  and  muscle  sense,  sight,  hearing  and  touch. 
These  areas  are  characterized  by  large  numbers  of  radial,  transverse 
and  projection  fibers  which  eventually  make  connection  with  the  more 
distant  projection  centers  apportioned  to  the  different  sensations 
and  motor  actions.  The  intermediary  fields  contain  fibers  which 
attain  their  medullary  sheath  during  the  first  month  of  extra-uterine 
life.  The  terminal  regions  possess  few  transverse  fibers,  but  numerous 
association  paths  which  unite  them  with  the  different  projection  cen- 
ters. They  form  the  association  areas  which  amplify  the  individual 
primary  sensory  centers  and  thus  form  the  memory  realms  for  vision, 
audition,  olfaction,  etc.  In  addition,  they  form  those  independent 
association  realms  which  give  rise  to  the  higher  psychic  concepts. 
For  this  reason,  they  may  be  regarded  as  the  organs  of  perception 
and  thought.  In  this  connection  it  should  be  stated,  however,  that 
many  physiologists  do  not  admit  that  the  highest  psychical  activities 
are  mediated  by  special  and  individualized  association  centers  (Munk), 
but  are  produced  in  the  association  realms  belonging  to  the  different 
primary  sensory  regions. 

1  Die  Lokalisation  der  geist.  Vorgange,  Leipzig,  1896;  also:  Sachs.  Gesellsch. 
der  Wissensch.,  Leipzig,  1904. 


700  THE    CEREBRUM 

Whichever  view  is  accepted,  it  must  be  evident  that  these  different 
association  regions  are  used  for  purposes  of  synthetizing  the  sensory 
impressions  into  perceptions  and  concepts.  In  accordance  with  Flech- 
sig,  it  may  thus  be  held  that  the  association  areas  are  the  places  in 
which  sense  impressions  are  built  up  into  organized  knowledge,  and 
whers  a  complex  mental  image  is  formed  of  conditions  in  our  internal 
and  external  world.  Typical  association  regions  are,  of  course,  the 
parieto-occipital  and  frontal  realms.  Regarding  the  latter,  little  prog- 
ress has  been  made.  It  has  been  stated  by  Bolton "^  that  mentally  defi- 
cient persons  (amentia)  exhibit  a  thinning  of  the  cortex  which  is  especially 
marked  in  the  frontal  region.  These  atrophic  changes  are  also  appar- 
ent in  idiotic  and  demented  persons;  in  fact,  it  is  claimed  that  they 
bear  a  direct  relationship  to  the  degree  of  the  idiocy.  Moebius^ 
calls  attention  to  the  fact  that  the  laterobasal  portions  of  the  frontal 
lobes  are  strongly  developed  in  mathematicians.  Thus,  the  brain  of 
Helmholtz  showed  a  uniform  massiveness,  but  especially  in  the  region 
between  the  gyrus  angularis  and  the  gyrus  temporalis  superior.^ 
According  to  Guzmann,*  the  gyrus  angularis  is  very  prominent  in 
people  who  possess  a  special  talent  for  music.  Mills^  argues  that  the 
intellectual  states  are  controlled  by  the  frontal  lobes,  while  Spitzka's" 
observations  rather  tend  to  prove  a  predominance  of  the  posterior 
association  fields  in  intellectual  men. 

Cases  of  extensive  destruction  of  the  frontal  lobes  have  been  cited 
repeatedly.  Most  commonly,  however,  reference  is  made  to  that  of  a 
workman  whose  frontal  lobes  were  extensively  lacerated  by  the  end  of  a 
crowbar,  driven  through  his  skull  by  a  premature  explosion  of  dynamite 
(1850).  In  aU  these  instances  a  decided  change  in  the  character  and 
intelhgence  of  the  individual  was  noted.  The  more  recent  observa- 
tions of  Phelps,^  Miiller^  and  Schuster,^  however,  have  shown  that  a 
deterioration  or  loss  of  the  higher  mental  qualities  does  not  always 
follow,  although  minor  mental  changes,  suchas  weakness  of  the  memory, 
insane  desires,  and  depression,  are  usually  present.  In  all  those  cases 
in  which  these  symptoms  were  the  result  of  circumscribed  tumors 
(glioma),  the  removal  of  the  growth  was  generally  followed  by  a  com- 
plete mental  recovery.  In  this  connection,  mention  should  also  be 
made  of  the  experiments  of  Franz i*'  which  have  proved  that  the  removal 
of  the  frontal  lobes  in  cats  and  monkeys  leads  to  the  loss  of  habits 
previously  formed  by  brief  periods  of  training.     The  habits  so  lost, 

1  Brain,  1903,  215,  and  1910,  26. 

2  tjber  die  Anlage  der  Mathematik,  Leipzig,  1900. 

3  Hansemann,  Zeitschr.  fiir  Psych,  der  Sinnesorgane,  xx,  1899,  1. 
*  Anat.  Anzeiger,  xix,  239. 

6  Univ.  of  Pennsylvania  Med.  Bull.,  xvii,  1904,  90. 
«  Med.  Record,  1901,  and  N.  Y.  Med.  Jour.,  1901. 
^  New  York  Med.  Jour.,  Ixi,  1895,  8. 
8  Allg.  Zeitschr.  fur  Psychiatrie,  lix,  1902,  830. 
^  Psych.  Storungen  bei  Hirntumoren,  1902. 
1"  Archives  of  Psychology,  March,  1907. 


CEREBRAL    LOCALIZATION  701 

may  be  rclojirned  in  about  the  same  period  of  time.  Lon^-standing 
habits,  on  the  other  hand,  seemed  to  be  retained,  in  spite  of  tlie  injury 
to  this  lobe. 

As  far  as  the  higher  functions  of  the  association  regions  are  con- 
cerned, much  work  must  still  be  done  to  obtain  more  definite  data. 
For  the  present,  we  can  go  no  further  than  to  state  that  tlu;  cortex  of 
the  cerebrum  is  the  seat  of  special  sensory  and  motor  projection  areas 
which  may  be  mapped  out  with  varying  definiteness.  We  are  also 
fairly  well  acquainted  with  the  sensory  and  motor  paths  leading  to  and 
away  from  these  regions.  Around  and  in  between  these  primary 
cortical  fields  certain  association  areas  are  situated  which  are  inti- 
mately connected  with  the  centers  to  which  they  belong,  and  in  turn 
also  with  one  another.  Their  destruction  affects  first  of  all  the  par- 
ticular sensory  or  motor  function  to  which  they  are  assigned,  and 
secondly,  the  functional  equilibrium  of  the  cerebrum  as  a  whole. 
This  constitutes  the  so-called  diaschisis  effect  of  Monakow,"^  consisting 
in  a  disturbance  of  the  dynamics  of  the  cerebral  processes  as  a  whole 
wliich,  however,  is  rather  transitory  in  its  nature. 

It  is  conceived  that  the  higher  mental  concepts  are  not  the  product 
of  special  areas  of  the  cortex,  but  are  the  result  of  discharges  of  nervous 
energy  from  one  center  to  another  as  well  as  to  more  remote  regions 
of  the  body.  This  interaction  of  nervous  energy  gives  rise  to  a  com- 
plex product,  the  analysis  of  which  is  at  present  impossible.  This 
constitutes  the  so-called  dynamic  theory  of  cortical  function,  in  accor- 
dance with  which  the  different  sensory  and  motor  centers  of  the  cere- 
brum are  to  be  regarded  merely  as  fixed  points  of  action  of  a  complex 
system  of  neurons  and  not  as  independent  generators  of  mental 
actions.  The  result  of  this  reverberation  of  discharges  through  the 
nervous  system  depends  in  each  case  upon  the  number  and  kind  of 
neurons  involved.  Thus,  the  higher  cortical  function  results  in  con- 
sequence of  the  correlation  of  its  different  products,  and  cannot  be 
ascribed  exclusively  to  one  or  the  other  of  its  constituent  areas. 

THE  CORPUS  CALLOSUM 

The  cerebral  hemispheres  are  connected  with  one  another  by  three 
tracts  of  commissural  fibers,  namely,  the  anterior  commissure,  the  for- 
nix, and  the  corpus  callosum.  The  most  conspicuous  of  these  is  the 
corpus  callosum  which  forms  the  floor  of  the  great  longitudinal  fissure 
and  may  be  brought  into  view  by  separating  the  hemispheres.  The 
fibers  composing  this  structure,  do  not  enter  the  main  paths  of  the 
internal  capsule,  but  extend  directly  across  from  cortex  to  cortex. 
According  to  Ferrier,^  Brown-Sequard,^  Koranyi,^  and  others,  its  divi- 
sion at  the  point  where  it  crosses  the  longitudinal  fissure,  is  not  followed 

1  Die  Lokalisation  des  Grosshirns,  Wiesbaden,  1914. 
-  Proc.  Royal  Soc,  London,  1875. 
^  Compt.  rend.  Soc.  biol.,  1887. 
^  Pfliiger's  Archiv,  xlvii,  1896,  35. 


702 


THE    CEREBRUM 


by  motor  or  sensory  defects  of  any  kind.  Mott  and  Schaeffer/ how- 
ever, have  shown  that  its  stimulation  gives  rise  to  symmetrical  move- 
ments on  the  two  sides  of  the  body.  Moreover,  there  is  sufficient 
experimental  evidence  at  hand  to  prove  a  distinct  localization  of  these 


^Central  fissure 

Posterior  central  gyrus 
Anterior  central  gyrus 


Corpus  callosum 
Fornix 
Lateral  ventricle 
Thalamus 

Caudate  nucleus 
Intfrnnl  capsule 


Lentiform  nucleus 
Insula 
Second  temporal  gyrus 
First  temporal  gyrus 


Claustrum 
Inferior  horn  of  lot.  vfnt. 

Hippocampal  fissure 

Optic  tract 
'Hippocampal  gyrus 

Uncus 
Cerebral  peduncle 
pons 
Pyramid  of  medulla  oblongata 


Fig.  350. — View   from   the   Front  of  a  Coronal  Section  of  an  Adult  Brain  Made 
Three  Inches  Behind  the  Frontal  Pole.      (J.  Symington.) 

fibers,  because  their  stmiulation  evokes  successively  movements  of 
the  eyes,  head,  trunk,  shoulder,  arm,  fingers,  hip,  tail  and  foot. 

Obviously,  therefore,  this  commissure  forms  a  connection  between 
the  two  motor  areas  for  the  association  of  symmetrical  points  of  these 
regions.     This  fact  may  be  substantiated  by  the  ablation  of  one  motor 

1  Brain,  xiii,  1890,  174. 


CEREBRAL    LOCALIZATION  703 

area,  when  the  excitation  of  the  corpus  will  evoke  movements  on  that 
side  of  the  body  which  is  still  connected  with  tlu;  uninjured  area. 
Although  generally  associated  with  idiocy  and  epilepsy,  certain  cases 
have  been  recorded  by  Wahler^  which  show  that  lesions  of  the  corpus 
callosum  in  man  give  rise  to  a  disturbance  of  the  muscular  movements. 
Liepman-  describes  cases  in  which  dyspraxia  existed  without  any  ap- 
parent injury  to  the  motor  cortex,  the  inference  being  that  this 
disorder  resulted  from  defects  in  the  power  of  conduction  of  the 
corpus. 

THE  BASAL  GANGLIA 

The  Corpus  Striatum. — The  nuclei  caudati  and  nuclei  lenticulares, 
constituting  the  corpora  striata,  are  intimately  connected  with  the  frontal 
cortex  by  the  corticocaudal  bundle  as  well  as  with  the  thalamus,  red 
nucleus,  and  through  the  latter  with  the  longitudinal  bundle.  They 
form,  therefore,  important  relay  stations  upon  these  paths  and  medi- 
ate reflexes  of  the  more  complex  kind.  In  the  lowest  vertebrates, 
these  bodies  form  almost  the  entire  telencephalon  and  really  serve  as 
the  basal  stem  from  which  the  hemispheres  of  the  higher  animals  are 
developed.  Their  importance  seems  to  be  greatest  in  the  birds, 
because  the  more  complex  processes  of  these  animals  appear  to  be 
mediated  by  these  bodies,  rather  than  by  the  palhum,  or  hemispheres. 

The  question  whether  they  possess  an  independent  function,  can- 
not be  answered  with  certainty,  because  their  destruction  by  means 
of  injections  of  chromic  acid,  as  well  as  their  stimulation,  has  yielded 
very  conflicting  results.  Their  close  connection  with  the  internal  cap- 
sule makes  a  direct  involvement  of  these  paths  not  improbable,  and 
hence,  many  of  the  effects  described  by  earlier  investigators^  may  be 
due  to  this  cause.  It  seems  to  be  established,  however,  that  these 
gangha  are  closely  associated  with  heat  production  and  the  regulation 
of  the  body  temperature,*  because  their  stimulation  invariably  results 
in  a  rather  lasting  rise  in  temperature,  amounting  to  as  much  as  1.6°  C. 
Mayer  and  Barbour  have  substantiated  these  results  by  permitting 
warm  and  cool  water  to  flow  upon  these  bodies.  Cooling  the  water 
produced  shivering  and  a  rise  in  the  body  temperature,  while  warming 
it  lowered  the  body  temperature. 

THE  THALAMUS  OPTICUS 

This  body  consists  of  three  parts,  known  as  the  median,  lateral, 
and  anterior  nuclei.  It  is  intimately  connected  with  the  corpus  stria- 
tum and  the  cerebral  cortex  by  ingoing  and  outgoing  fibers,  and  also 
forms  the  end-station  of  the  secondary  sensory  tracts  of  the  spinal  cord 

1  Balkentumoren,  Leipzig,  1904. 

2  Med.  Klinik,  1907,  725. 

3  Schuller,  Zentralbl.  fiir  Physiol.,  1902,  222. 

*  Jto.,  Archiv  fiir  Physiol.,  1898,  537,  and  Zeitschr.  fiir  Biologie,  xxxciii,  1898, 36; 
also  Nicolaides  and  Dontas,  Archiv  fiir  Physiol.,  1911,  249. 


704  THE    CEREBRUM 

and  medulla  oblongata.  In  addition,  its  pulvinar  prominences,  to- 
gether with  the  lateral  geniculates  and  anterior  corpora,  form  the  end- 
station  of  the  primary  division  of  the  optic  tract,  while  the  median 
geniculates  and  posterior  corpora  receive  the  auditor^-  tract.  It  is 
also  connected  with  the  cerebellum,  and  sends  a  few  fibers  to  the  red 
nucleus  and  medulla  oblongata.^ 

In  accordance  with  its  connections  with  the  cutaneous,  sensory, 
optic  and  auditory  tracts,  ?^Ionakow-  regards  the  thalamus  opticus, 
together  with  the  lateral  and  median  geniculates,  as  a  subsidiary  cere- 
bral cortex,  the  purpose  of  which  is  to  transfer  these  sensations  to  the 
proper  association  areas.  Lesions  of  this  body,  therefore,  mast  give 
rise  to  very  diverse  sj-mptoms.  This  also  holds  true  of  the  outgoing 
impulses.  Bechterew,^  for  example,  calls  attention  to  the  loss  of  the 
emotional  movements  concerned  with  laughing  and  crying,  and  the  im- 
pairment of  the  mimic  play  of  the  facial  muscles.  This  investigator 
also  states  that  this  body  contains  the  reflex  center  for  the  secretion  of 
the  tears.  Its  activation  also  produces  a  dilatation  of  the  pupils,  a 
bulging  of  the  eyeballs  and  a  retraction  of  the  eyelids.  Injury  to  this 
body  also  gives  rise  to  the  so-called  phenomenon  of  Romberg,  i.e., 
to  an  inabihty  to  stand  erect  when  the  eyes  are  closed.  This  sjonptom 
serves  as  a  diagnostic  sign  in  tabes  dorsaUs  and  other  degenerative 
affections  of  the  nervous  system.^ 

THE  CORPORA  QUADRIGEMINA 

The  anterior  corpora  receive  a  part  of  the  optic  fibers  and  direct 
them  to  the  cortex  of  the  occipital  lobes.  The  posterior  corpora,  to- 
gether with  the  median  geniculates,  serve  as  end-stations  of  the  second- 
ary auditorv'  fibers,  and  communicate  with  the  cortex  of  the  temporal 
lobes  and  other  parts  of  the  cerebrum.  In  the  lower  forms,  the  destruc- 
tion of  these  bodies  occasions  blindness  in  both  eyes,  while  their 
unilateral  laceration  gives  rise  to  blindness  either  in  the  corresponding 
eye  or  in  that  of  the  opposite  side.  This  diversity  in  the  effects  is  caused 
by  differences  in  the  crossing  of  the  optic  fibers.  In  the  monkeys  and 
man,  bhndness  does  not  result,^  for  the  reason  that  the  loss  of  these 
relay  stations  is  compensated  for  by  a  transfer  of  their  optic  impulses  to 
other  tracts. 

The  anterior  corpora  contain  the  center  for  the  constriction  of  the 
pupils,  the  impulses  being  transferred  in  this  place  from  the  optic  tract 
to  that  of  the  oculomotor.  Furthermore,  this  transfer  is  distinctly 
reciprocal,  because  the  stimuli  brought  to  bear  upon  the  retina  of  one 

1  Wallenberg,  Neurol.  Zentralblatt,  xx,  1901,  50. 

2  Gehirnpathologie,  Wien,  1904. 

3  Xeurol.  Zentralblatt,  x,  1894,  481. 

^  Wilbrand  and  Sanger,  Die  Neurologie  des  Auges,  Wiesbaden,  1904;  also 
Sachs,    Brain,   i,    1909. 

^  Deutsche  Zeitschr.  fiir  Ner\-enheilkunde,  xvii,  1900,  428. 


CEREBKAL    LOCALIZATION  705 

eye,  affect  both  pupils  in  a  corresponding  degree.  It  necxi  scarcely  be 
emphasized,  therefore,  that  the  occipital  cortex  may  be  removed  with- 
out destroying  the  light-reflex.  An  injury  to  the  posterior  corpora 
produces  deafness  in  some  animals,  but  not  in  monkeys.  ^  These  bodies 
also  exert  an  inhibitor  influence  upon  reflex  action  and  are  concerned 
with  the  orderly  execution  of  movements.  This  is  true  especially  of 
fishes,  amphibians  and  reptiles,  in  which  animals  these  functions  are 
centered  in  the  corpora  ))igemini,  also  known  as  the  optic  lobes. 

1  Ferrier  iind  Turner,  Brain,  cciv,  1900,  27. 
45 


SECTION  XIX 

THE  CEREBELLUM.     THE  PROTECTIVE  MECHAN- 
ISMS OF  THE  NERVOUS  SYSTEM 


CHAPTER  LVII 

THE  CEREBELLUM 

The  Structure  of  the  Cerebellum. — Anatomists  have  been  accus- 
tomed to  divide  this  organ  into  a  median  lobe  or  vermis  and  a  right 
and  left  lateral  lobe,  or  hemisphere.     Bolk,^  however,  does  not  recog- 


Sulcus  prepyramidah 
Sulcus  pregracilis 


Tonsilla 

Lobulua  biventralit 


Lobulvs  postero-superior 
Lobulua  gemilanaria  inferior 
Lobulua  gracilis  posterior 
Lobulus  gracilis  anterior 
Pyramis 

Fig.  351. — View  of  Cerebelll-m  from  Below.     (J.  Syminoton.) 


Sutctis  intragracilis 
Sulcus  postgracilis 
Sulcus  horizontalis  magnum 


nize  this  transverse  arrangement,  but  advocates  a  division  in  the 
anteroposterior  direction.  Thus,  it  is  stated  that  the  sulcus  primarius 
separates  this  organ  into  an  anterior  and  a  posterior  portion.  The 
former  embraces  the  superior  vermis,  the  montieulus  and  lobus  quad- 
ratus  anterior,  while  the  latter  includes  the  remaining  portion  of  this 
organ,  namely,  the  lobulus  simplex,  lobulus  medianus  posterior  (ver- 
mis inferior)  and  the  lobuli  comphcati. 

1  Das  Cerebellum  der  Sjiugetiere,  Jena,  1906. 
706 


THE  STRUCTURE  OF  THE  CEREBELLUM 


707 


The  external  surface  of  the  coroliplluin  presents  numerous  deep  furrows  or 
sulci  which  Uniit  narrow  leaf-Uke  gyri  or  convohitions.  Thus,  when  cut  trans- 
versely across,  tiie  section  presents  a  number  of  lamelhe,  or  leaf-like  subdivisions, 
which  bear  a  close  reseml)lance  to  the  spri{!;s  of  the  evergreen  cedar  tree,  designated 
as  arbor  vitic.  Each  lamella  is  made  up  of  a  central  core  of  white  matter  and  an 
external  envelope  of  gray  matter.  Tlie  latter  consists  of  three  layers.  At  the  point 
of  contact  between  the  cortical  gray  and  the  white  matter  lies  a  broad  zone  of  very 
minute  granular  cells.  These  elements  possess  a  scanty  amount  of  cytoplasni  and 
very  short  claw-like  dendrites.  Their  axones  are  thin  and  non-meduUated,  and 
connect  with  the  constituents  of  the  superficial  molecular  layer.  Here  they  divide 
into  two  branches  which  pursue  a  course  parallel  to  the  longitudinal  axis  of  the 
lamellae  and  terminate  among  the  dendrites  of  the  cells  of  Purkinje,i  composing  the 


Cuhnen 


Sulcus  predival 


Sulcus  poatcentralis 

precentralis 


Sulcus  postcli 
Folium  racuinin! 
Sulcus  horizonialis 
maffii  us 


ivalis  -;   ffySw 


tV 


Sulcus precentrcdis    \ 

Lingula 

Sup.  Tjied.  velum 

Dorsal  recess  of 
ith  venti: 


Tuber  valvules 
Sulcus  pos'tpyramidalis 


Uvula 


(5^  -si 

s  g 

Fig.  352. — Medl\n  Section  of  the  Worm. 
Sagittal  section  of  the  cerebellum  to  show  its  internal  structure,  the  relative  depth 
of  the  fissures,  and  the  grouping  of  the  laminse.      (Schafer.) 

central  layer.  The  cells  just  mentioned  are  the  most  characteristic  constituents  of 
the  cerebellar  cortex.  They  present  large  pear-shaped  bodies  and  a  bushy  fan- 
shaped  network  of  dendrites,  which  is  directed  transversely  to  the  long  axis  of  the 
lamellae.  Their  axons  are  mj-elinated  and  form  the  chief  efferent  path  between  the 
cortex  of  the  cerebellum  and  the  more  deeply  seated  nuclei,  to  be  described  later. 
The  most  external  zone  is  known  as  the  molecular.  It  is  occupied  by  the  dendrites 
of  the  cells  of  Purkinje  and  those  of  the  cells  of  the  granular  laj^er.  A  few  neurons 
are  interposed  in  this  place  for  purposes  of  association.  The  most  characteristic  of 
these  are  the  so-called  basket  cells. 

The  fibers  composing  the  white  matter  are  of  three  kinds — two  afferent  and  one 
efferent.  The  former  pass  either  directly  into  the  molecular  layer  where  they 
terminate  among  the  dendrites  of  the  cells  of  Purkinje,  or  extend  only  as  far  as  the 

^  Named  after  their  discoverer,  Johannes  Purkinje,  Professor  of  Physiology  at 
Breslau,  from  1822  to  1850. 


708 


THE    CEREBELLUM 


cells  of  the  granular  layer.  The  long  ascending  ones  are  known  as  tendril  fibers 
and  the  short  ones  as  moss  fibers,  so-called  on  account  of  the  peculiar  thickenings 
which  they  exhibit  close  to  their  points  of  termination.  Ramon  y  Cajal  believes 
that  the  tendrils  are  the  terminals  of  the  fibers  of  the  middle  peduncle,  while  the 
moss  fibers  are  derived  from  the  afferent  fibers  of  the  inferior  peduncle.  The 
efferent  fibers  are  formed  by  the  axons  of  the  cells  of  Purkinje.  They  end  in  the 
deep  nuclei,  whence  their  impulses  are  conveyed  onward  by  secondary  neurons. 


Fig.  353. — Section    of    Cortex   of       Fig 


PuRKiKJE    Cell,    of    the 


Cerebellum. 
a,  Pia  mater;  b,  exterior  layer;  c, 
layer  of  cells    of   Purkinje;  d,   inner 
or  granular  layer ;  e,  medullary  center. 

(Sankey.) 


Cerebellar  Cortex.     Golgi  Method. 

a,  Axon;  b,  collateral;  c,  d,  ramifications 

of  dendrons.      (Cajal.) 


The  cerebellum  also  contains  certain  collections  of  gray  matter  beneath  its 
cortex.  Within  the  vermis  and  above  the  fourth  ventricle  are  found  the  so-called 
roof  ganglia,  consisting  of  the  nuclei  fastigii  situated  near  the  middle  line,  the 
nuclei  emboliformes  located  in  a  dorsal  direction  from  the  former,  and  the  nuclei 
globosi.  Directly  embedded  in  the  white  matter  of  the  hemispheres  are  the  deep 
nuclei  of  which  the  nuclei  dentati  are  the  most  conspicuous.  As  has  been  stated 
above,  the  latter  form  stations  upon  the  efferent  paths,  and  the  former  stations  upon 
the  afferent  paths.  Each  incoming  fiber  divides  into  many  branches  and  is  thus 
brought  into  relation  with  the  greatest  possible  number  of  cells  of  the  granular  layer. 


THE    CONNECTIONS    OF    THE    CEREBELLUM 


709 


The  peculiar  position  of  the  latter  toward  the  cellsof  Purkinjc  {i;ives  rise  to  very  close 
and  niultit'orin  synapses  so  that  the  widest  possible  raniilications  are  established. 
Functionally,  this  intricate  union  of  the  dilTerent  neurons  greatly  facilitates  the 
spreading  and  summation  of  impulses,  and  leads  to  the  so-called  avalanche  conduc- 
tion, i.e.,  to  an  unusually  extensive  involvement  of  neurons. 

The  Connections  of  the  Cerebellum. — The  cerebellum  is  expanded 
upon  a  central  stem  formed  by  its  three  connecting  strands  of  fibers, 
which    are   known   as   the   superior,    middle   and    inferior   peduncles. 


Fig.  355.  Fig.  356. 

Fig.  355. — Ba,sk£t-work  op  Fibers  Around  Two  Cells  of  Purkinje. 

a.  Axis-cylinder  or  nerve-fiber  process  of  one  of  the  corpuscles  of  Purkinje;  h,  fibers 
prolonged  over  the  beginning  of  the  axis-cylinder  process;  c,  branches  of  the  nerve-fiber 
processes  of  cells  of  the  molecular  layer  felted  together  around  the  bodies  of  the  cor- 
puscles of  Purkinje.     (Cajal.) 

Fig.  356. — Figure  Showing  the  Three  Pairs  of  Cerebellar  Peduncles. 

On  the  left  side  the  three  cerebellar  peduncles  have  been  cut  short;  on  the  right 
side  the  hemisphere  has  been  cut  obliquely  to  show  its  connection  with  the  superior 
and  inferior  peduncles.  The  cut  ends  of  the  cerebellar  peduncles  have  been  artificially 
separated  from  one  another  and  are  displayed  diagrammatically.  1,  Median  groove 
of  the  fourth  ventricle;  2,  the  same  groove  at  the  place  where  the  auditory  striee  emerge 
from  it  to  cross  the  floor  of  the  ventricle;  3,  inferior  peduncle  or  restiform  body;  4, 
funiculus  gracilis;  5,  superior  peduncle:  on  the  right  side  the  dissection  shows  the 
superior  and  inferior  peduncles  crossing  each  other  as  they  pass  into  the  white  center 
of  the  cerebellum;  6,  lateral  fillet  at  the  side  of  the  pedunculi  cerebri;  7,  lateral  grooves 
of  the  pedunculi  cerebri;  8,  corpora  quadrigemina.  (From  Sappey  after  Hirschfeld  & 
Leveille.) 

The  superior  peduncle  is  made  up  very  largely  of  fibers  which  arise  in  the  dentate 
nuclei  and  pass  toward  the  region  of  the  midbrain.  The}^  cross  the  midline  below 
the  corpora  quadrigemina  and  connect  with  the  red  nucleus  and  the  optic  thalamus. 
The  afferent  fibers  of  this  peduncle  are  few  in  number  and  seem  to  be  derived  from 
the  thalamus. 

The  middle  peduncle  is  made  up  chiefly  of  afferent  fibers  which  are  derived  from 
the  nuclei  of  the  pons.  They  cross  the  midline  within  this  structure  and  pass  into 
the  lateral  cerebellar  hemisphere  of  the  opposite  side.  A  certain  number  of  fibers 
also  extend  efferently  from  the  cerebellum  into  the  same  region  of  the  pons.  In  this 
way,  a  connection  is  formed  with  the  corticopontine  fibers  which  brings  the  cere- 


710 


THE    CEREBELLUM 


bellum  into  relation  with  the  cortex  of  the  frontal  and  parietal  lobes  of  the  opposil^e 
side.  The  middle  peduncle  also  embraces  efferent  fibers  which  are  derived  from 
the  cells  of  Purkinje  and,  after  their  decussation  in  the  pons,  descend  in  the  lateral 
funiculus  of  the  cord.  They  eventually  terminate  around  the  motor  cells  of  the 
anterior  horns. 


^erebeUum 


Tr  olivo<ereb. 

tr.spino- 
cereb.  dors 

(Ficchsig) 


bi-achium 
conjurcrivum 

Tr  TecTo-ceveb 

,tr.  ponTo-ceretx 

mesencephalon 


Tv  spino-olivar 
tr  coi^tico-spinalis^ 


cenWal 

Tegmental 

Tract. 

Tr.  cortico- 
olivQ  inferior  pontdi's 

tr  spino- cereb  ventr.  (Gowers) 


Fig.  357. — Diagram  of  the  CnrEF  Afferent  Tracts  Leading  into  the  Cerebelll'M. 

(Herrick.) 

The  inferior  peduncle  is  composed  principally  of  afferent  fibers  which  take  their 
origin  either  in  the  spinal  cord  or  in  the  bulb.  The  former  constitute  the  continua- 
tion of  the  direct  cerebellar  tract  and  ascend  through  the  corpus  restiforme  into  the 
vermis  of  the  cerebellum.  ^     We  have  seen  that  this  tract  includes  the  axons  of  the 


cerebellum 


nuc.  dentatus 

roof  nuclei 
corpus  restiforme 


rachium    pontis 

brachium 

conjunctivum 

tr.  cereb.-tegmentalis 
ephali 


■mesencephalon 

rubro-thol. 


diva  inferior- 


-Ti^  rubro- 
spinalis 

Tr  cerebeilo- 

tegmenTalis 

pontis 

tr.  cerebello-tegmentdis   buibi 


Fig.  357o. — Diagram  of  the  Chief  Efferent  Tr.\cts  leading  out  of  the  Cerebellvm. 

(Herrick.) 

cells  of  Clark's  column  and  collaterals  from  the  posterior  roots  of  the  cord.  The 
medullary  fibers  form  the  continuation  of  the  vestibular  division  of  the  auditory 
nerve  and  connect  the  nuclei  of  Deiters  and  Bechterew  with  the  nucleus  fastiguus 


1  Thomas,  Le  Cervelet,  Paris,  1897. 


THE    ABLATION    OF    THE    CEREBELLUM  711 

and  nucleus  globosus  of  the  cerebellum.  In  this  way,  this  orRan  Is  brought  into  rela- 
tion with  the  semicircular  canals  of  the  internal  ear.  It  also  receives  a  few  fibers 
from  the  trigeminus,  vagus  and  accessory  nerves.  The  efferent  fibers  of  the  in- 
ferior peduncle  arise  in  the  dentate  nucleus  and  form  the  direct  anterolateral  bundle 
which  connects  with  the  spinal  tracts. 

The  Ablation  of  the  Cerebellum. — The  size  and  complexity  of  the 
cerolK'llum  dilViT  greatly  in  diiferent  animals.  It  reaches  its  highest 
development  in  the  apes  and  man.  In  these  animals  we  also  find  the 
greatest  relative  development  of  the  cerebrum,  although  these  organs 
do  not  display  a  perfect  structural  correspondence.  We  have  seen 
that  the  cerebral  cortex  is  made  up  of  complexes  of  neurons  which  show 
very  decided  differences  in  their  structure  and  arrangement,  and  medi- 
ate different  nervous  processes.  The  cerebrum,  therefore,  presents 
unmistakable  evidence  of  a  division  of  function.  A  precise  localiza- 
tion of  this  kind  is  not  in  evidence  in  the  cerebellum.  On  the  contrary, 
this  organ  exhibits  a  decidedly  homogeneous  structure,  and  hence,  we 
cannot  go  wrong  in  assuming  that  it  possesses  a  single  specific  func- 
tion. The  correctness  of  this  conclusion  will  become  more  apparent 
later  on. 

While  repeated  attempts  have  been  made  by  Rolando  (1809), 
Flourens  (1824),  Magendie  (1825),  Vulpian  (1866),  Nothnagel  (1876), 
and  others,  to  apply  to  the  cerebellum  the  methods  previously  used 
in  experiments  upon  the  cerebrum,  the  results  have  proved  very 
unsatisfactory  on  account  of  the  difficulties  which  surgical  interferences 
\vith  this  organ  must  necessaril}'  be  confronted  by.  Subsequent  to 
the  time  of  Galvani  and  Volta,  when  an  undue  stress  was  placed 
upon  the  electrical  phenomena  in  nature,  it  was  believed  that  the 
cerebellum  supphes  the  ''nerve  force"  which  is  required  for  our  bodily 
processes.  No  doubt,  this  now  ridiculous  contention  w\as  based  chiefly 
upon  the  observation  that  the  lamellated  outline  of  this  organ  in  cross- 
section  presents  certain  characteristics  which  remind  one  of  the  Vol- 
taic pile.  Later  on  Gall  advocated  the  hypothesis  that  it  is  concerned 
with  the  sexual  emotions.  The  first  tangible  view  of  its  function  was 
presented  by  Flourens,  who  regarded  it  as  an  organ  for  the  coordination 
of  muscular  movements  and  particularly  of  those  concerned  in  locomo- 
tion and  the  preservation  of  the  equilibrium. 

This  view  is  widely  accepted  to-day  and  finds  its  origin  in  the  array 
of  symptoms  displayed  by  pigeons  whose  cerebellar  hemispheres 
have  been  removed  either  in  part  or  in  their  entirety.  Birds,  in  par- 
ticular, are  closely  dependent  upon  a  properly  balanced  muscular 
apparatus,  inclusive  of  its  central  coordinating  mechanism,  the  cere- 
bellum. It  may  be  inferred,  therefore,  that  the  excessive  development 
of  this  organ  noted  in  these  animals,  is  in  keeping  with  their  muscular 
power,  and  that  its  removal  must  give  rise  to  especially  disturbing 
symptoms.  Thus  we  find  that  a  pigeon  deprived  of  its  cerebellar 
hemispheres,  shows  a  spasdic  position  of  the  wings,  legs  and  head  which 
renders  standing,  walking  and  flying  impossible.     Any  attempt  to 


712  THE    CEREBELLUM 

make  it  move  results  in  excessive  and  asymmetrical  muscular  contrac- 
tions which  make  it  tumble  in  all  directions.  It  is  to  be  noted,  however, 
that  this  loss  of  the  power  of  coordinated  movement  is  not  caused  by 
a  paralytic  condition  of  the  different  muscles  but  by  an  inabilitj'  to 
correlate  their  actions  for  the  attainment  of  a  particular  purpose. 
This  swaying,  staggering  behavior  constitutes  the  condition  of  ataxia. 
It  is  true,  however,  that  these  symptoms  are  not  permanent,  but  grad- 
ually disappear  in  the  course  of  time  until  merely  a  certain  unsteadiness 
in  the  gait  is  left  behind.  In  reptilia  and  amphibia  the  cerebellum 
is  rudimentary.  It  cannot  surprise  us,  therefore,  to  find  that  its 
ablation  produces  no  noticeable  defects  in  these  animals. 

Luciani^  has  extended  these  experiments  to  the  mammals.  He 
states  that  a  dog,  after  unilateral  removal  of  the  cerebellum,  shows  a 
rigidity  of  the  extremities,  a  curvature  of  the  spine  toward  the  operated 
side  (opisthotonos),  a  deviation  of  the  head  toward  the  normal  side, 
a  slight  nystagmus,  and  strabismus.  The  latter  condition  presents 
itself  as  a  deviation  of  the  eyes  downward  and  inward  on  the  operated 
side,  and  upward  and  outward  on  the  normal  side.  Among  the 
dynamic  symptoms  are  mentioned  atonia,  or  loss  of  the  tonus  of  the 
musculature,  asthenia,  or  loss  of  force,  astasia,  or  loss  of  steadiness, 
and  ataxia,  or  loss  of  the  purposeful  action  of  the  musculature.  These 
defects  are  chiefly  unilateral  and  produce  forced  movements  toward 
the  abnormal  side.^  The  latter  consist  in  rolling  motions  toward  the 
injured  side  as  well  as  in  movements  in  a  circle  toward  the  same  side. 
Most  generally,  however,  the  more  intense  symptoms  disappear  in 
the  course  of  from  eight  to  ten  days  and  are  superseded  bj'  tremors. 
The  general  character  of  these  defects  as  well  as  their  rather  short 
duration,  led  Luciani  to  assume  that  the  cerebellum  is  an  organ  which 
by  processes  that  remain  below  the  threshold  of  consciousness,  produces 
a  reinforcement  of  the  activity  of  the  musculomotor  centers.  In 
this  belief,  however,  he  merely  followed  the  views  of  du  Petit  (1710), 
Laf argue  (1838),  and  others. 

A  number  of  cases  are  on  record  of  inherited  defects  of  the  cere- 
bellum in  man,  as  well  as  of  tumors  which  in  the  course  of  time  de- 
stroyed large  segments  of  this  organ. ^  The  symptoms  noted  in  these 
persons,  show  a  decided  similarity  to  those  observed  in  the  lower 
mammals.  Briefly  stated,  cerebellar  disease  produces  a  condition 
of  asynergia,  i.e.,  an  inabihty  properly  to  associate  movements  of 
greater  or  less  complexity  into  functionally  definite  acts.  If  we  adhere 
to  this  view,  that  the  cerebellum  is  the  seat  of  synergia,  this  organ 
assumes  a  position  very  similar  to  that  of  an  association  center  of  the 
cerebrum.  It  then  becomes  the  center  for  the  coordination  of  aU 
muscular  activity  by  reason  of  its  power  of  associating  those  sensory 
impulses  upon  which  movements  depend. 

1  Arch.  ital.  de  Physiol.,  xxi,  1894;  Fisiol.  et  Pathol,  del  Cer\-elletto,  Padova, 
1897,  and  Ergebn.  der  Physiol.,  iii,  1904,  259. 

2  Eckhard,  Herrmann's  Handb.  der  Physiol.,  ii,  1883,  102. 

^  Mills  and  Weisenburg,  Jour.  Am.  Med.  Assoc,  Nov.  21,  1914. 


CEREBELLAR    LOCALIZATION  713 

The  asynergia  dovoloixnl  in  the  course  of  cerobellar  disorders,  pre- 
sents itself  in  various  forms,  namely,  as: 

(a)  Hypermetry,  or  clLsmetry,  i.e.,  a  faulty  measurement  of  the  movements. 
In  this  particular  instance,  the  patient  is  unal)le  to  associate  the  motor  constituents 
of  such  acts  as  putting  the  index  finger  to  the  tip  of  the  nose  when  the  eves  are 
closed.  Invuriablv,  the  finger  misses  its  mark  by  a  distance  which  increases  with 
the  degree  of  the  hvpernlctrJ^ 

{b)  Adiadochokinesis,  or  an  inabiUty  to  produce  fine  motor  associations  of  an 
antagonLstic  character.  This  is  shown  by  the  fact  that  the  patient  is  quite  unable 
to  pronate  and  supinate  the  hand  when  the  forearm  Ls  flexed  upon  the  arm. 

(r)  Tremors,  shown  in  grasj^ing  for  objects  or  in  walking.  The  gait  is  trunkal, 
i.e.,  the  trunk  constantly  leaves  its  accustomed  position,  V:)ut  is  immediately  sup- 
ported in  its  new  place  by  the  legs  in  a  stilt-like,  sprawling  manner.  The  cere- 
bellar patient,  however,  knows  his  difficulty  and  makes  compensatory  movements 
to  counteract  these  forced  movements.  In  this  regard  he  differs  very  decidedly 
from  a  person  who  is  under  the  influence  of  alcohol.  The  latter  reels  in  any  direc- 
tion without,  at  least  in  the  final  stage,  being  able  to  antagonize  his  movements. 
This  loss  of  compensation  is  due,  of  course,  to  the  fact  that  the  alcohol  has  rendered 
the  cerebral  centers  inactive.  Cerebellar  defects,  on  the  other  hand,  need  not  be 
accompanied  by  cerebral  depression.  The  cerebellar  patient  also  exhibits  an  asyn- 
ergia  of  the  tongue  and  laryngeal  muscles  which  gives  rise  to  a  jerky  and  crackling 
speech.  The  head  is  generally  carried  in  the  plane  of  the  trunk.  The  eyes  are 
seldom  at  rest. 

(d)  Atonia,  or  loss  of  tonus  and  relaxation  of  the  muscles.  This  condition  is 
dependent  upon  the  fact  that  the  tonic  impulses  from  the  cerebral  cortex  cannot 
become  effective  when  the  movements  are  asynergic. 

(e)  Asthenia,  or  loss  of  force.  This  condition  is  due  to  the  exhaustion  which 
results  whenever  the  efforts  to  perform  purposeful  movements  can  no  longer  be 
properly  controlled. 

(/)  AsUisia,  or  loss  of  steadiness. 

(g)  Ataxia,  or  loss  of  the  purposeful  action  of  the  muscles.  This  is  a  complex 
s\Tnptom  resulting  in  consequence  of  the  other  defects. 

Cerebellar  Localization. — It  has  been  shown  by  Ferrier  that  the 
stimulation  of  the  surface  of  the  hemispheres  of  the  cerebellum  or  of 
its  superior  vermis,  gives  rise  to  movements  on  the  same  side  of  the 
body.  In  order  to  evoke  these  motor  results,  it  becomes  necessary  to 
use  much  stronger  stimuli  than  are  ordinarily  required  for  the  excitation 
of  the  cortex  of  the  cerebrum.  This  observation  is  in  keeping  with 
the  histological  arrangement  of  the  cerebellar  neurons,  because  the 
cortex  is  really  the  end  station  of  the  afferent  paths,  while  the  efferent 
paths  as  such  begin  in  the  more  deeply  seated  nuclei. 

Naturally,  when  we  speak  of  localization  of  function  in  the  cere- 
bellum, we  realize  that  this  organ,  contrary  to  the  cerebrum,  mediates 
only  one  kind  of  activity,  namely,  that  of  coordinating  the  movements 
of  skeletal  muscle.  Thus,  the  only  question  before  us  is,  whether 
different  muscles  or  groups  of  muscles  are  controlled  by  different  regions 
of  this  organ.  That  such  a  division  of  labor  actually  exists,  has  been 
shown  very  clearly  by  the  experiments  of  Horsley  and  Clarke^  which 
yielded  movements  of  the  eyes  and  head  on  excitation  of  the  roof  nuclei, 
and  movements  of  the  trunk  and  limbs  on  stimulation  of  the  para- 

1  Brain,  xxviii,  190.5,  13. 


714 


THE    CEREBELLUM 


cerebellar  nuclei  (Deiters').  Very  similar  results  have  been  obtained 
by  destroying  circumscribed  areas  of  the  cerebellar  cortex.  Thus, 
it  has  been  observed  by  Ryerberk^  that  the  excision  of  the  lobulus 
simplex  produces  forced  movements  of  the  head  (head-nystagmus),  a 
condition  which  is  caused  by  a  faulty  control  of  the  muscles  of  the 
neck.  Quite  similarly,  the  destruction  of  the  ansiform  lobule  next  to 
the  crus  primum,  gives  rise  to  a  disordered  action  of  the  muscles  of  the 
foot  of  the  same  side,  while  lesions  of  the  crus  secundum  cause  a  dis- 
turbance in  the  movements  of  the  foot.     In  accordance  with  the  older 


/\CL 


schema  of  Bolk,  the  present  state  of  cere- 
bellar localization  may  be  represented  as 
in  Fig.  358,  A  and  B.  Stress  should,  how- 
ever, be  laid  upon  the  general  fact  that 
different  areas  of  the  cerebellum  control 
different  groups  of  muscles,  rather  than 
upon  the  kind  of  muscle  actually  domi- 
nated by  any  particular  area  of  this  organ. 
The  observations  of  Holmes^  upon 
soldiers  suffering  from  lacerations  and  gun- 
shot wounds  of  different  portions  of  the 
cerebellum,  have  failed  to  yield  positive 
results.  In  many  of  these  cases,  however, 
the  exact  location  of  the  lesion  could  not 
be  made  out.  It  is  true  that  injuries  to 
the  vermis  most  generally  produced  affec- 
tions of  the  n  uscles  of  the  head,  neck  and 
trunk,  including  those  of  phonation  and 
articulation.  Small  superficial  lesions  pro- 
duced only  slight  and  transient  symptoms 
which  involved  whole  limbs  rather  than 
particular  muscles,  but  the  defects  were 
invariably  limited  to  the  side  of  the  lesions. 
But,  though  these  clinical  observations  do 
not  lend  support  to  the  physiological  con- 
tention that  the  localization  in  the  cere- 
bellum is  perfectly  definite,  they  cannot 
be  considered  as  proof  that  such  a  minute  localization  does  not  exist. 
The  Function  of  the  Cerebellum. — The  foregoing  data  pertaining  to 
the  ablation  and  excitation  of  the  cortex  and  intrinsic  nuclei  of  the 
cerebellum,  have  been  employed  repeatedly  as  a  possible  basis  for 
a  more  precise  doctrine  regarding  the  function  of  this  organ.  But 
while  the  general  activity  of  this  organ  is  clearly  discernible,  physi- 
ologists have  not  succeeded  as  yet  in  detecting  the  precise  nature  of  the 
mechanism  by  means  of  which  it  is  able  to  consummate  its  action. 
It  has  been  stated  above  that  Flourens  regarded  this  organ  as  a  center 

lErgebn.  der  Physiologie,  vii,  1908,  643,  and  xii,  1912,  533. 
2  Brain,  xl,  1918,461. 


Fig.  358. — Diagram  Illustrat- 
ing Cerebellar  Localization. 
A,  Upper  surface  and  B, 
lower  surface  of  human  cere- 
bellum; PrF,  primary  fissure; 
PcF,  postcleval  fissure;  GLF, 
great  longitudinal  fissure;  GHF, 
great  horizontal  fissure;  PF, 
pyramidal  fissure;  ACL,  anterior 
crescentic  lobe;  SSL,  superior 
semilunar  lobe;  JSL,  anterior 
semilunar  lobe;  BL,  biocentral 
lobe. 


THE    FUNCTION    OF    THE    CEREBELLUM  715 

for  the  coordination  of  voluntary  niovomonts,  while  Rolando  (1809), 
Weir  ]\Iitchell  (1809),  and  Luciani  considered  it  as  an  organ  for  the 
reinforcement  of  the  activity  of  the  musculomotor  centers  of  the 
cerebrum  and  spinal  cord.  Munk  ascribed  to  it  the  function  of 
preserving  the  cquilibi'ium  of  the  body,  while  Hitzig  saw  in  it  the 
association  center  of  the  muscle  sense.  The  last  view  has  been 
advocated  more  recently  by  Lewandowsky^  and  Sherrington. 

In  last  analysis  we  are  dealing  here  with  a  reflex  or  excitomotor 
function  of  the  cerebellum,  in  consequence  of  which  the  musculature 
of  our  body  is  forced  to  act  within  perfectly  definite  channels.  We 
obtain  an  absolutely  set  condition  of  tonus,  a  certain  amplitude  of 
contraction,  and  a  coordination  of  the  activities  of  the  different  muscles. 
Thus,  the  only  factor  to  be  determined  as  yet  is  the  intrinsic  stimulus 
which  causes  the  cerebellum  to  discharge  these  regulatory  impulses. 
In  the  nature  of  this  process,  the  latter  may  be  either  acceleratory 
or  inhibitory. 

In  accordance  with  the  view  of  Lussana,  Hitzig  and  Lewandowsky, 
the  cerebellum  is  to  be  regarded  as  the  center  for  the  muscle-sense, 
in  which  the  different  centripetal  impulses  from  these  sense  organs 
are  associated  to  give  rise  to  coordinated  motion.  This  association, 
however,  does  not  involve  consciousness,  as  does  the  association 
taking  place  in  the  cerebral  centers,  but  remains  subconscious,  or 
more  correctly  speaking,  reflex  in  its  nature.  Sherrington  has  gone 
a  step  farther  and  designates  this  organ  as  the  head  ganglion  of 
the  proprioceptive  system,  in  which  the  different  impulses  from  the 
muscle-spindles  and  from  the  labyrinth  are  brought  together  and  asso- 
ciated subconsciously.  From  here  the  resulting  impulses  are  conveyed 
through  the  superior  peduncle  into  the  cerebrum,  where  they  influence 
the  function  of  the  motor  areas.  Other  impulses  are  made  to  travel 
outward  by  way  of  its  connections  with  the  pons  and  bulb,  and  to 
direct  the  activity  of  the  distant  musculature.  In  this  way,  a  com- 
plex mechanism  is  established  which  is  concerned  with  the  coordina- 
tion of  the  musculature  in  general,  but  more  particularly  with  that 
having  to  do  with  the  maintenance  of  the  equilibrium  of  the  body 
as  its  position  in  space  is  changed  to  suit  particular  purposes. 

lArchiv  fur  Physiol.,  1903,  129. 


716  THE    CEREBELLUM 


CHAPTER  LVIII 

THE  PROTECTIVE  MECHANISMS  OF  THE  NERVOUS 

SYSTEM 

SLEEP  AND  NARCOSIS 

The  Enveloping  Membranes. — The  encephalon  is  contained  in  a 
rigid  box  formed  by  the  cranial  bones.  The  periosteal  lining  of  the 
latter  is  displaced  by  the  dura  mater,  a  strong  fibrous  membrane 
which  is  lined  internally  with  endothelial  cells,  and  sends  firm  parti- 
tions inward  for  the  support  and  protection  of  the  different  parts  of 
the  brain.  A  membranous  process  of  this  kind  invades  the  great 
longitudinal  fissure  separating  the  hemispheres  of  the  cerebrum. 
It  is  called  the  falx  cerebri,  because  it  possesses  the  shape  of  a  sickle, 
being  narrow  in  front  and  broad  behind.  Another,  the  tentorium 
cerebelli,  extends  transversely  across  between  the  cerebrum  and  cere- 
bellum, while  a  third,  the  falx  cerebeUi,  clips  into  the  fissure  between 
the  cerebellar  hemispheres.  In  several  places,  the  dura  mater  is 
split  into  two  layers  for  the  reception  of  the  sinuses  which  return  the 
blood  from  the  brain.  In  the  spinal  canal,  the  dura  is  not  attached 
to  the  bone,  but  forms  a  long  extended  sac  which  closely  invests  the 
spinal  cord  and  is  held  in  place  by  the  prolongations  which  pass  out- 
ward to  invest  the  individual  spinal  roots.  Its  outside  surface  is 
covered  with  networks  of  veins. 

Directly  underneath  the  dura  and  in  intimate  contact  with  it, 
lies  a  delicate  transparent  membrane,  known  as  the  arachnoid.  Its 
outer  surface  is  covered  with  endothelial  cells  and  borders  upon  the 
subdural  space  which,  in  reality,  is  of  capillary  size  and  does  not  seem 
to  have  a  special  functional  significance.  Its  under  surface  is  placed 
in  relation  with  the  pia  mater,  but  in  such  a  way  that  a  distinct  cleft 
arises  between  them  which  is  known  as  the  subarachnoidal  space. 
The  latter  is  intersected  by  fine  fiber  connections  and  septa  of  con- 
nective tissue,  the  meshes  of  which  are  filled  with  a  lymph-like  fluid. 
It  becomes  especially  conspicuous  over  the  different  sulci  for  the 
reason  that  the  pia  mater  follows  the  surface  of  the  brain  into  these 
furrows,  while  the  arachnoid  and  dura  pass  directly  across  them  in  the 
form  of  bridges.  In  certain  localities,  however,  the  subarachnoid 
space  is  much  increased  in  size,  forming  here  the  so-called  cisternae  which 
in  turn  are  connected  with  one  another  by  delicate  canals.  Reflections 
of  the  arachnoid  frequently  dip  into  the  fissures.  One  of  these  is 
found  between  the  cerebral  hemispheres  and  the  third  ventricle, 
where  it  extends  into  the  lateral  ventricle,  becoming  covered  on  one 
side  by  the  ependyma  of  this  cavity,  and,  on  the  other,  by  the  epen- 
dyma  of  the  roof  of  the  third  ventricle.     It  envelops  a  rich  network 


PROTECTIVE    MECHANISMS    OV   THE    NERVOUS    SYSTEM       717 

of  blood-vessols  forming  the  choroid  plexus.     A  similar  vascular  fring(! 
is  suspended  from  the  roof  of  the  fourth  ventricle. 

This  subarachnoid  system  is  in  direct  communication  with  the 
ventricles  of  the  biain  by  way  of  the  foramen  of  Magendie  and  the 
foramina  of  Luschka.  It  also  connects  with  the  lymphatic  spaces 
accompanying  the  cranial  nerves,  as  well  as  with  the  central  canal  tra- 
versing the  commissure  of  the  gray  matter  of  the  spinal  cord.  In 
addition,  it  is  placed  into  relation  with  the  venous  sinuses  by  the 
Pacchionian  bodies.  The  latter  are  pouch-like  protrusions  from  the 
surface  of  the  arachnoid  formed  l)y  enlargements  of  the  normal  villi 
of  this  membrane.     Most  of  these  ])odics  are  lodged  in  irregular  pits 


Fig.  359. — Trans\t:rse  Section  Through  the  Longitudinal  Fissutie  to  show  the 
Relation  of  the  Cerebrlm  to  the  Meninges. 
C.C,  Corpus  callosum;  TT',  white  matter;  G,  cortical  gray  matter;  P,  pia  mater 
closely  investing  it;  A,  arachnoid  with  its  membranous  prolongations  forming  the 
subarachnoid  space  (S.S.);  D,  dura  mater;  B,  skull  consisting  of  the  external  and 
internal  plates  separated  by  a  spongy  center;  F,  falx  cerebri  enveloping  LS,  the  longi- 
tudinal sinus.     Into  the  latter  extend  the  Pacchionian  bodies. 

in  the  calvaria,  but  some  of  them  also  project  into  the  sinuses.  They 
are  particularly  numerous  along  the  superior  longitudinal  sinus.  The 
close  contact  which  is  thus  estabUshed  between  the  liquid  fiUing  this 
entire  system  and  the  venous  blood,  might  lead  us  to  suppose  that  these 
saccules  serve  as  a  means  for  returning  some  of  the  liquor  to  the  blood. 
They  do  not,  however,  constitute  perfectly  open  outlets,  and  hence  the 
escape  of  the  lymph  must  be  brought  about  very  largely  by  processes 
of  filtration  and  osmosis. 

The  Growth  of  the  Brain. — Broca^  states  that  the  weight  of  the  pia 
mater  amounts  to: 

1  Elements  d'Anthropologie  generale,  1885. 


718  THE    CEREBELLUM 

45  grams  in  individuals  between  the  ages  of  20-30 
50  grams  in  individuals  between  the  ages  of  30-40 
60   grams  in   individuals   between  the  ages  of   50-60 

The  capacity  of  the  ventricles  is  26  c.c,  and  the  specific  gravity  of 
the  entire  encephalon  1.036.  Its  weight  varies  considerably  even  when 
members  of  the  same  race  and  social  standing  are  compared.  Thus, 
the  compilations  of  Marshall^  which  are  based  on  the  records  of 
Boyd,  show  immediately  that  the  male  possesses  a  heavier  encephalon 
than  the  female  and  that  all  its  subdivisions  are  heavier.  Further- 
more, a  comparison  of  individuals  of  the  same  sex  and  age  will  show 
that  those  having  the  greater  stature,  exhibit  a  greater  brain  weight, 
and  that  the  weight  decreases  with  advancing  years.  This  decrease 
in  weight  is  most  clearly  indicated  between  the  seventy-first  and 
ninetieth  years. 

Vierordt^  has  collected  a  series  of  observations  illustrating  the 
changes  in  the  weight  of  the  brain  between  birth  and  the  twenty-fifth 
year,  which  show  that  the  greatest  increase  takes  place  during  the 
first  year.  It  grows  rapidly  to  the  fourth  and  fifth  years,  and  then 
more  gradually  to  the  seventh  year.  From  this  time  on  its  growth  is 
very  slight  up  to  maturity.  Social  environment  may  be  expected  to 
be  of  influence,  because  the  least  favored  individuals  in  any  community 
usually  show  a  certain  retardation.  The  observations  of  Manouvrier 
have  proved,  however,  that  the  average  weight  of  the  brains  of  murder- 
ers permits  of  no  conclusions  when  compared  with  the  average  weight 
of  the  brains  of  the  usual  inmates  of  hospitals.  Moreover,  with  the 
exception  of  the  microcephahcs,  the  insane  as  a  class  are  not 
characterized  by  an  especially  slight  brain  weight.  The  examination 
of  the  brain  capacities  of  a  series  of  skulls  belonging  to  different 
races,  favors  the  western  Europeans.^ 

The  total  number  of  neurons  present  in  the  central  nervous 
system,  has  been  estimated  at  13,000,000,000.  This  estimate  is 
based  upon  the  records  of  Hammarberg,'*  which  in  accordance  with 
Thompson,^  give  9,200,000,000  well-marked  cell-bodies  to  the  cortex 
of  the  cerebrum  alone. 

The  Cerebrospinal  Fluid.^ — The  subarachnoidal  and  subdural 
spaces,  as  well  as  the  encephalic  ventricles,  are  filled  with  a  colorless 
liquid,  the  quantity  of  which  varies  between  60  and  200  c.c.  in  accord- 
ance with  the  age  and  size  of  the  individual.  The  subdural  space 
being  chiefly  potential,  about  one-half  of  this  quantity  is  held  in  the 
subarachnoidal  clefts,  and  20-30  c.c.  in  the  ventricles     We  have  noted 

1  Jour,  of  Anat.  and  Physiol.,  1892. 

2  Archiv  fiir  Anat.  u.  Physiol.,  1890. 

2  Davies,  Jour,  of  the  Acad,  of  Nat.  Sciences,  Philadelphia,  1869;  also:  Donald- 
son, The  Growth  of  the  Brain,  1895. 

*  Studien  tiber  die  Path,  der  Idioten,  Upsala,  1895. 

6  Jour,  of  Comp.  Neurol.,  1899. 

^  First  described  by  Haller,  Physiol,  des  Menschen,  1766. 


PROTECTIVE    MECHANISMS    OF    THE    NERVOUS    SYSTEM       719 

beforo  that  this  subarachnoichil  space  does  not  possess  the  same  height 
throughout  the  encephalon,  but  shows  cistern-Kke  enlargements  at 
different  points,  and  especially  over  the  corpus  callosum  and  the  optic 
lobes.  Over  the  upper  and  lateral  aspects  of  the  brain  it  is  very  nar- 
row. It  has  also  been  mentioned  that  it  is  traversed  by  numerous 
fibers  and  bands,  so  that  it  really  becomes  subdivided  into  a  multitude 
of  intercomnmnicating  cells  which  in  turn  connect  with  the  lateral 
ventricles,  the  central  canal  and  subarachnoidal  space  of  the  spinal 
cord,  the  lymphatic  channels  of  the  cranial  and  spinal  nerves,  and  the 


Fig.  360. — Right  Lateral  Aspect  of  the  Skull  and  Cerebral  Hemisphere  Out- 
lined IN  Black,  with  Orthogonal  Projection  of  the  Structures  in  the  Median  Plane 
AND  OF  the  Right  Lateral,  the  Third  and  the  Fourth  Ventricles  in  Red.     (jQuain.) 

Man  aged  fifty-six  years,  a,  nasion;  h,  bregma;  c,  lambda;  d,  union;  t.r.,  temporal 
ridge;  s.c,  sulcus  centralis;  s.p..  Sylvian  point. 

lymphatics  of  the  nasal  cavity  and  neck.^  It  seems,  however,  that 
the  subdural  and  subarachnoidal  spaces  are  not  directly  connected 
with  one  another,  although  colored  fluid  injected  into  either  cavity, 
eventually  reaches  the  lymphatics  of  the  nasal  cavity  as  well  as  those 
of  cranial  nerves. 

Cerebrospinal  fluid  may  be  obtained  from  animals  by  introducing 
a  cannula  through  a  slit  in  the  sheath  of  a  nerve  root  into  the  subarach- 
noid space  of  the  spinal  canal  or  by  inserting  it  through  the  atlanto- 
occipital  membrane  into  the  cistern-Hke  enlargement  of  the  subarach- 
noid over  the  fourth  ventricle.  In  man,  it  is  now  a  rather  common 
procedure  to  introduce  a  hollow  needle  directly  into  the  spinal  canal 

1  Walter,  Monatschrift  fur  Psych,  und  Neurol.,  1910,  28. 


720  THE    CEREBELLUM 

of  the  lumbar  region,  the  needle  being  pushed  inward  between  the 
laminae  of  the  vertebrae.  This  constitutes  the  procedure  of  lumbar 
puncture^  which  is  made  necessary  whenever  small  quantities  of  this 
fluid  are  to  be  obtained  for  chemical  and  histological  analysis.  Several 
cases  are  also  on  record,  showing  that  a  spontaneous  discharge  of  cere- 
brospinal liquid  may  take  place  at  times  from  the  nasal  cavity,  aver- 
aging as  much  as  500  c.c.  in  24  hours. 

The  fact  that  this  fluid  escapes  from  the  cannula  with  some  force 
snows  that  it  is  held  under  a  certain  pressure,  equaling  5  to  7.3  mm.  Hg. 
The  flow  decreases  later  on  until  only  droplets  appear.  Various  symp- 
toms, such  as  vertigo,  nausea  and  headache,  result  if  it  is  allowed  to 
drain  off  for  too  long  a  time.  It  is  also  of  interest  to  note  that  the 
pressure  of  this  fluid  is  about  equal  to  that  existing  in  the  venous  sinu- 
ses of  the  cranial  cavity.  Thus,  if  salt  solution  is  injected  into  the 
subarachnoid  space,  it  will  be  found  to  escape  with  relative  ease,  one 
of  its  channels  of  escape  being  the  Pacchionian  bodies.  It  seems, 
therefore,  that  these  protrusions  of  the  arachnoid  membrane  serve  as 
filters,  allowing  a  quick  interchange  of  pressure  between  the  cerebro- 
spinal fluid  and  the  blood  in  the  sinuses.  A  similar  interchange  may 
be  effected  between  this  fluid  and  the  lymph  filUng  the  lymphatics  of 
the  nerve  roots,  but  the  resistance  interposed  here  seems  to  be  much 
greater. 

The  cerebrospinal  fluid  is  commonly  regarded  as  a  true  secretory 
product  (Mott)  of  the  epithelial  Hning  cells  of  the  choroid  plexus 
(Luschka).  Others,  however,  consider  it  as  a  lymphatic  fluid  formed 
by  transudation  as  well  as  by  secretion  (Lewandowsky).  It  cannot  be 
doubted  that  this  fluid  possesses  a  certain  independency,  because  bil- 
iary pigments  frequently  appear  in  the  content  of  the  subarachnoid 
space  but  not  in  that  of  the  ventricles;  and  furthermore,  the  former 
often  shows  certain  chemical  characteristics  which  are  not  displayed 
by  the  latter. ^  It  has  also  been  found  that  its  flow  may  be  increased 
by  extract  of  choroid  plexus.^  Its  formation,  however,  is  slow  under 
ordinary  conditions,  as  has  been  shown  by  the  experiments  of  Cavaz- 
zani,^  which  prove  that  it  takes  about  one  hour  before  an  easily  recog- 
nizable salt  injected  into  the  general  circulatory  channels,  may  be  de- 
tected in  the  subarachnoid  fluid. ^  In  a  similar  way,  it  has  been  found 
that  potassium  iodid  injected  into  the  encephalic  arachnoid  cavity,  ap- 
pears in  the  urine  only  after  about  twenty  minutes.  In  view  of  this 
close  connection  between  the  cerebrospinal  fluid  and  the  IjTnph,  it 
seems  best  to  consider  the  former  as  being  derived  from  three  sources, 
namely,  (a)  by  secretion  into  the  ventricle  from  the  choroid  plexus,  (6) 

^  Quincke,  Deutsche  med.  Wochenschrift,  1905. 
2  Thomson,  The  Cerebrospinal  fluid,  New  York,  1899. 
2  HaUiburton,  Proc.  R.  Soc,  London,  1916. 
^  Centralbl.  fiir  Physiol.,  xiii,  1-1. 

^  Plaut,  Rehm  and  Schottemiiller,  Leitfaden  zur  Unters.  der  Zerebrospinal- 
fliissigkeit,  Jena,  1913. 


PROTECTIVE    MECHANISMS    OF    THE    NERVOUS    SYSTEM       721 

by  transudation  into  the  suliarachnoid  and  subdural  spaces,  and  (c)  by 
transfer  from  tlie  intra-advcntitial  Ijnnphatic  spaces  of  the  cortex. 

Regarding  its  function  it  should  b(i  mentioned  first  of  all  that  it 
serves  1h(>  genci-al  purpose  of  lympii,  because  it  bathes  the  n(;rve-cells. 
It  forms  a  nutritive  medium,  which,  in  addition,  is  chemically  protect- 
ive, because  it  tends  to  exclude  such  harmful  substances,  as  proteins 
and  toxins.  In  the  second  place,  it  is  mechanically  protective,  be- 
cause it  serves  as  a  water-})iHl  ujwn  which  rests  the  base  of  tlie  middle 
and  posterior  parts  of  the  encephalon,  and  which  in  other  regions  mini- 
mizes the  force  of  blows  upon  the  integument.  In  the  third  place,  it 
may  be  conjectured  that  this  fluid  subjects  the  nervous  tissue  to  a 
certain  pressure  which  keeps  it  under  a  tension  best  adapted  for  its 
function. 

Sleep.  ^ — Activity  must  always  be  followed  by  rest,  because  con- 
tinued catabolic  processes  lead  to  fatigue  and  exhaustion.  This  holds 
true  of  the  motor  as  well  as  of  the  sensory  mechanism.  A  heart  or 
skeletal  muscle,  Avhen  made  to  contract  repeatedly,  soon  loses  its  irri- 
tability, because  it  is  not  allowed  sufficient  time  to  replenish  the  mate- 
rial lost  during  its  periods  of  activity.  This  is  also  true  of  glands  if 
made  to  secrete  excessively,  and  of  all  sense-organs,  if  stimulated  for  a 
long  period  of  time.  What  is  true  of  individual  tissues,  is  true  of  the 
body  as  a  whole.  It  requires  a  period  of  recuperation  during  which  its 
receptive  power  is  at  a  minimum  and  during  which  it  reestablishes 
proper  physico-chemical  conditions.  Sleep  is  a  universal  phenomenon 
among  animals;  even  the  fish,  reptiles  and  amphibians  pass  long 
periods. of  time  in  absolute  quietude.  The  fundamental  reason  for 
sleep  must,  of  course,  be  sought  in  chemico-physical  changes,  but  our 
present  knowledge  of  metabohsm  is  not  sufficiently  advanced  to  ex- 
plain the  cause  of  this  phenomenon  in  more  than  a  very  general 
manner. 

While  the  daily  requirement  of  sleep  is  about  7-8  hours  for  the 
adult,  this  time  varies  considerably  under  different  conditions.  In 
childhood,  the  amount  of  stored  energy  is  small,  owing  to  the  immature 
development  of  the  cells,  while  the  metabohsm,  relatively  rated,  is 
intense,  and  hence,  children  require  longer  periods  for  recuperation. 
In  old  age,  on  the  other  hand,  the  small  amount  of  stored  energy  is  due 
rather  to  retrogressive  changes  and  is  associated  with  a  lower  meta- 
bohsm, both  factors  combining  to  produce  shorter  hours  of  sleep.  In 
either  case,  however,  loss  of  sleep  is  injurious  and  even  more  so  than 
the  AA-ithholding  of  nourishment.  Thus,  Manaceine^  has  found  that 
3^oung  dogs  may  withstand  a  starvation  period  lasting  twenty  days, 
but  fail  to  recover  from  a  loss  of  sleep  extending  over  more  than  four  or 
five  days.  These  animals  exliibited  a  fall  in  the  body  temperature  of  as 
much  as  8°  C.  below  normal,  a  diminution  of  the  reflexes,  fatty  de- 
generation of  diverse  tissues,  and  hemorrhagic  extravasations  into  the 

1  Picron,  Le  probleme  physiol.  du  sommeil,  Paris,  1913. 

2  Contemp.  Science  Series,  London,  1897. 
46 


722  THE    CEREBELLUM 

nervous  tissue.  Very  similar  changes  have  been  observed  in  men 
deprived  of  sleep  during  a  period  of  ninety  hours.  ^ 

The  desire  to  sleep  most  commonly  manifests  itself  by  drowsiness, 
a  general  malaise,  a  heaviness  and  dryness  of  the  eyelids,  a  difficulty 
in  keeping  the  attention  fixed,  and  other  symptoms.  This  initial 
state  soon  gives  way  to  a  condition  of  unconsciousness  during  which  the 
cortex  is  at  least  moderately  impervious  to  external  and  internal 
stimuli.  All  volitional  actions,  therefore,  cease,  while  the  reflexes  are 
in  part  preserved,  although  greatly  diminished  in  their  intensity. 
This  shows  that  some  parts  of  the  central  nervous  system  remain  more 
active  than  others  and  this  is  true  even  of  the  cerebral  cortex,  because 
the  motor  center  becomes  inactive  before  the  sensations  have  been 
lost  entirely.  Thus,  a  person  may  have  reached  the  state  of  muscular 
flaccidity  while  still  capable  of  receiving  sensations  of  sound  and  touch. 

The  sense-organs  themselves  are  in  part  protected  against  stimuli. 
The  eyelids  are  closed  and  the  eyeballs  rolled  far  upward  and  inward. 
The  pupils  are  markedly  diminished  in  size.  The  latter  effect  may  be 
explained  in  the  same  manner  as  the  constriction  resulting  on  near 
vision,  i.e.,  it  may  be  said  to  find  its  cause  in  afferent  stimuli  set  up  in 
consequence  of  the  convergence  of  the  eyes.  The  conjunctival  mem- 
brane becomes  dry  owing  to  a  diminished  secretion  of  lacrimal  fluid, 
and  is  thus  rendered  less  responsive  to  stimuli.  A  similar  diminution 
in  the  sensitiveness  is  noted  in  the  oral  and  nasal  cavities.  Their 
mucous  lining  also  exhibits  a  certain  dryness  as  a  result  of  diminished 
secretion.  The  ears  are  protected  by  a  relaxation  of  the  conductors 
of  sound  situated  in  the  middle  ear,  i.e.,  the  ear  drum  and  ossicles. 

Sleep  having  set  in,  the  respirations  become  slower  and  deeper  and 
are  frequently  accompanied  by  loud  noises  produced  by  the  air  as  it 
rushes  across  the  relaxed  fauces,  uvula,  and  edges  of  the  laryngeal  folds. 
In  many  cases  the  respirations  assume  a  periodic  character,  a  certain 
number  of  them  being  separated  from  others  by  a  distinct  interval  of 
comparative  rest.  The  frequency  of  the  heart  is  greatly  reduced;  the 
vascular  channels  are  relaxed  and  the  blood  pressure  lessened.  From 
these  changes  it  may  justly  be  inferred  that  the  tissues  have  entered 
upon  a  state  of  relative  inactivity;  their  low  oxygen  requirement  and 
small  output  of  carbon  dioxid  clearly  betrajdng  a  decided  reduction  in 
their  oxidations. 

Changes  in  the  Depth  of  Sleep. — Although  sleep  lasts  as  a  rule  for 
a  certain  number  of  hours,  it  does  riot  retain  the  same  depth  through- 
out this  period.  This  has  been  shown  by  endeavoring  to  awaken  a 
person  at  different  intervals  by  sounds  of  measured  intensity.  A  pen- 
dulum beating  against  a  metal  plate,  or  small  lead  balls  falling  upon  a 
metal  surface,  have  usually  been  used  for  this  purpose. ^  While  in- 
dividual variations  are  very  common,  the  results  show  that  the 
intensity  of  sleep  increases  steadily  until  it  reaches  its  maximum 

1  Patrick  and  Gilbert,  Psyehol.  Review,  iii,  1896. 

2  Monninghoff  and  Piesbergen,  Zeitschr.  fiir  Biologie,  xix,  1883. 


PROTECTIVE    MECHANISMS    OF   THE    NERVOUS    SYSTEM       723 

between  the  first  and  second  hours  after  its  beginning.  It  then 
decreases  and  remains  rather  hght  during  the  third  and  fourth  hours. 
A  second  but  much  shghter  increase  takes  place  during  the  fifth  hour. 
From  here  on  it  again  (U^creases  up  to  the  hour  of  awakening. 

Theories  of  Sleep. — The  theories  pertaining  to  the  causation  of  sleep, 
may  be  conveniently  arranged  as  follows : 

(a)  Aneinia  Theory  (Coppie,  1854). — It  is  held  that  the  diminution  and  loss 
of  the  irritability  of  the  cerebrum,  and  especially  of  its  cortical  zone,  is  dependent 
upon  a  decrease  in  its  blood-supply.  This  view  is  based  chiefly  upon  the  experi- 
ments of  Mosso^  which  have  shown  that  the  volume  of  the  arms  and  legs  increases 
during  sleep,  presumably  on  account  of  a  transfer  of  blood  from  the  cerebral  into 
the  cutaneous  circulatory  channels.  This  transfer  may  be  effected  in  two  ways, 
namely,  by  a  constriction  of  the  cerebral  blood-vessels ^  or  by  a  relaxation  of  the 
blood-vessels  in  other  parts  of  the  body.  The  extracerebral  circuits  which  could 
be  concerned  in  producing  this  diminution  in  the  vascularity  of  the  brain,  are  those 
of  the  integument  and  portal  organs. 

These  facts  have  been  made  use  of  by  HilP  in  formulating  a  theory  which  has 
as  its  chief  element  the  fatigue  of  the  vasomotor  center.  It  is  assumed  that  sleep 
results  in  consequence  of  the  loss  of  tonus  of  this  center  brought  on  by  the  con- 
tinued activity  during  the  working  hours.  This  loss  of  the  vascular  tonicity  in 
turn  leads  to  lower  pressures  and  diminishes  the  blood  flow  throughout  the  body 
but  more  particularly  that  through  the  brain.  The  blood  withdrawn  from  the 
cerebral  circuit,  is  said  by  Hill  to  be  accommodated  in  the  blood-vessels  of  the  portal 
organs,  while  Howell  believes  that  it  is  transferred  into  those  of  the  skin  and  sub- 
cutaneous tissues.  Brodmann'*  and  Shepard-'  however,  claim  that  the  volume  of 
the  brain  is  increased,  during  sleep,  as  is  also  that  of  the  limbs.  This  contradiction 
of  the  results  of  the  investigators  just  cited,  necessitates  a  certain  modification  of 
the  anemia  theory,  because  it  places  the  transfer  of  blood  from  the  brain  into  other 
blood-vessels  into  question.  At  best,  therefore,  we  can  go  no  further  thanto  state 
that  the  vascular  relaxation  and  depression  resulting  during  sleep,  is  general  and 
does  not  produce  an  actual  anemic  condition  of  the  brain. 

(b)  Inhibition  theory,  advocated  by  Brown-Sequard,  "^  refers  sleep  to  an  inhibition 
of  cortical  function,  such  as  may  be  produced  by  passing  an  induction  current  of 
low  tension  through  the  cranium  (Leduc).  This  view  has  few  points  in  its  favor, 
because  it  does  not  attempt  to  explain  the  mechanism  by  means  of  which  this 
inhibition  is  brought  about. 

(c)  The  mechanical  block  theory  refers  sleep  to  an  interruption  of  the  conduction 
paths  caused  by  a  retraction  of  the  terminal  fibers  of  the  synapses.'  This  view 
must  also  be  said  to  contain  a  decided  element  of  speculation,  because  it  has  never 
been  demonstrated  that  a  retraction  of  this  kind  actually  takes  place. 

(d)  The  chemical  theories  of  Preyer,*  Pieron^  and  Pflligeri''  refer  the  loss  of  the 
irritability  of  the  brain  to  a  fatigue  brought  on  by  chemical  means.     Thus,  it  has 

1  Ueber  den  Kreislauf  des  Blutes  im  menschl.  Gehirn,  Leipzig,  1881;  also: 
Brush  and  Fayerweather,  Am.  Jour,  of  Physiol.,  v,  1901,  199. 

2  Jensen,  Pfliiger's  Archiv,  ciii,   1903,   171. 

2  Physiol,  and  Pathol,  of  the  Cerebral  Circulation,  London,  1896,  and  Howell, 
Jour,  of  Exp.  Med.,  ii,  1897,  313. 

*  Jour,  fiir  Psych,  und  Neurologie,  i,  1902,  10. 

5  Am.  Jour,  of  Physiol.,  xxiii,  1909. 

«  Archiv  de  physiol.,  1889,  333. 

'  Duval,  Compt.  rend,  de  la  Soc.  biol.,  1895;  Cajal,  Archiv  fiir  Anat.  und  Phy- 
siol., 1895,  and  Nicard,  Le  sommeil  normal,  Lyon,  1904. 

^  Centralb.  f.  d.  med.  Wissensch.,  xiii,  1875. 

^  Le  probldme  physiol.  du  sommeil,  Paris,  1913. 
"  Pfluger's  Archiv,  x,  1875,  468. 


724  THE    CEREBELLUM 

been  suggested  that  the  constant  activity  of  the  muscles  and  other  organs  during 
the  waking  hours  gives  rise  to  waste  products  which  accunudate  in  the  system, 
because  they  cannot  be  gotten  rid  of  as  rapidly  as  they  are  produced.  In  the  course 
of  time,  these  substances  cause  a  nervous  depression  tv'hich  eventually  culminates 
in  sleep.  While  this  theory  also  lacks  experimental  confirmation,  it  has  certain 
points  in  its  favor.  Thus,  it  is  a  well-known  fact  that  the  activity  of  muscle  is 
associated  with  the  production  of  fatigue  substances,  such  as  carbon  dioxid,  sar- 
colactic  acid  and  monopotassium  phosphate.  The  accunudation  of  these  sub- 
stances in  muscle  finally  causes  the  latter  to  lose  its  irritability.  Furthermore,  if 
the  serum  of  a  fatigued  animal  is  injected  into  the  circulatory  channels  of  a  normal 
animal,  the  latter  will  show  all  the  phenomena  of  fatigue. 

Some  physiologists,  among  them  Pioron,  have  gone  a  step  farther  and  have  stated 
that  these  fatigue  substances  are  augmented  by  a  special  toxin  which  might  be 
designated  as  a  hypnotoxin.  It  is  this  agent  which  is  assimied  to  produce  the 
histological  changes  in  the  cells  of  the  brain  after  forced  deprivation  of  sleep.  Its 
presence  has  been  established  by  injecting  the  blood  senmi  or  cerebrospinal  fluid 
of  such  animals  into  the  circulatory  channels  of  normal  animals.  The  latter  then 
showed  a  condition  simulating  sleep  as  well  as  structural  changes  in  the  cerebral 
cortex. 

Pfliiger  explains  sleep  by  assuming  that  the  cells  of  the  brain  are  quite  unable 
to  replace  their  store  in  intramolecular  oxygen  as  rapidly  as  it  is  used  up  and  hence, 
their  irritability  must  decrease  gradually  with  the  length  of  the  period  of  activity. 
This  idea,  however,  that  oxygen  is  stored  in  the  cells  as  a  product  of  a  distinct 
synthesis  is  not  commonly  accepted  to-day.  The  foregoing  brief  discussion  must 
show  that  this  subject  is  still  in  a  very  indefinite  form,  so  that  it  might  seem  advisa- 
ble to  adhere  for  the  present  to  the  chemical  theory  and  to  consider  the  changes  in 
the  pressure,  flow  and  distribution  of  the  blood  as  secondary  phenomena. 

Hypnotic  Sleep. — This  condition  is  by  no  means  identical  with 
sleep.  It  is  brought  about  by  producing  the  picture  of  hypnosis  by 
suggestion,  a  process  which  may  be  greatly  facilitated  by  fixing  the 
attention  of  the  subject  upon  a  constant  visual,  auditory  or  tactile 
stimulus,  such  as  a  glistening  object,  a  monotonous  sound,  or  slight 
stroking  of  the  skin.  Facilitation  of  this  process  is  effected  in  time  by 
repeated  hypnoses  until  eventually  a  condition  of  autohypnosis  may  be 
induced,  i.e.,  an  ability  on  the  part  of  a  person  to  self-induce  this  state 
(Cardanus,  1553). 

Contrary  to  sleep,  the  hypnotized  person  exhibits  a  decided  blanch- 
ing of  his  features,  a  muscular  relaxation,  a  drooping  of  his  eyelids, 
slow  and  deep  respirations  and  a  peculiar  change  in  his  conscious- 
ness which  is  characterized  by  a  decided  vulnerabihty  to  suggestions. 
The  vascular  changes  are  betrayed  by  a  decrease  in  the  volume  of 
the  arms  and  legs,  when  determined  by  means  of  the  phlethysmograph. 
Deep  hypnosis,  moreover,  insures  a  loss  of  voluntary  control  of  the 
muscles  and  certain  sensory  disturbances,  such  as  amnesia,  analgesia 
and  anesthesia  for  touch  and  temperature.  Curiously  enough,  this 
loss  of  the  self-regulation  of  muscular  movements  does  not  include  the 
control  of  the  voluntary  muscles  through  suggestion.  Thus,  it  is 
possible  to  force  a  hypnotized  person  to  assmne  different  positions  or 
to  inhibit  the  action  of  his  muscles,  so  that  he  cannot  extricate  hunself 
from  the  most  awkward  idiomuscular  situations.  In  fact,  his  muscles 
may  be  tonically  set,  so  that  the  body  becomes  perfectly  rigid  and  may 


PROTECTIVE    MECHANISMS    OF    THE    NERVOUS    SYSTEM       725 

be  subjected  to  most  unusual  conditions.  Quite  similarly,  it  is  pos- 
sible to  influence  his  mental  concepts  in  such  a  way  that  memories 
of  certain  past  experiences  are  lost,  while  others  are  artificially  created, 
thereby  changhig  the  entire  character  of  the  person.  He  may  assume 
the  character  of  a  typical  paralj-tic,  bhnd  or  deaf  person.  Some  of 
these  suggestions  may  even  produce  posthjT^notic  results  many  days 
and  weeks  after  the  hypnosis.  Thus,  when  a  postage  stamp  was  placed 
upon  the  skin  of  a  hypnotic  and  it  was  suggested  to  him  that  it  would 
raise  a  blister,  such  a  formation  was  actually  found  beneath  it  on  the 
following  day.  Subcutaneous  hemorrhages  may  be  induced  in  the 
same  way,  and  so  may  "brand-marks"  by  simply  suggesting  to  the 
hypnotic  that,  say,  a  piece  of  chalk  used  upon  the  skin,  is  a  red  hot 
iron. 

Hypnotic  states  may  also  be  evoked  in  animals.  Thus,  it  is  not 
difficult  to  render  frogs,  birds  and  rabbits  motionless  by  a  continued 
gentle  pressure  upon  the  dorsal  aspect  of  their  body,  such  as  may  be 
produced  by  holding  them  in  the  pahn  of  the  hand.  A  lobster  may  in 
this  way  be  made  to  stand  upon  its  head  supported  only  by  the  first 
pair  of  appendages.  Kircher's  experimentum  mirabile  (1644)  con- 
sists in  rendering  a  fowl  temporarily  quiescent  by  placing  a  straw  across 
its  bill  or  by  fixing  its  head  in  such  a  way  that  the  eyes  look  directly 
at  a  chalk  fine  drawn  across  the  table.  Verworn,^  however,  states 
that  this  is  not  an  instance  of  true  hypnosis  but  solely  one  of  optical 
inhibition  of  reflexes. 

Narcosis. — Omitting  the  largely  speculative  theories  regarding 
the  causation  of  narcosis,  it  has  always  been  supposed  that  the  nar- 
cotics enter  into  a  chemical  combination  with  the  constituents  of  the 
protoplasm.  In  analogy-  to  this  union  might  be  mentioned  the  action 
of  curarin  upon  the  motor  nerve-endings  or  that  of  carbon  monoxid  upon 
the  hemoglobin.  Peculiarly  enough,  certain  narcotics  of  the  aliphatic 
series  are  chemically  inactive,  although  capable  of  inducing  a  character- 
istic narcotic  action.  It  was  subsequently  found  that  all  possess  the 
property  of  being  dissolved  in  water  and  fats,  this  property  being 
responsible  for  their  absorption  and  distribution  to  the  cells  of  the 
body.  Bibra  and  Harless,^  therefore,  conceived  the  idea  that  the  action 
of  the  anesthetics  is  dependent  upon  their  power  of  dissolving  fat.  This 
hypothesis,  however,  seems  untenable,  because  it  fails  to  explain  the 
rapid  restitution  of  function  following  the  anesthetization.  In  other 
words,  it  seems  unlikely  that  the  fat  dissolved  out  of  the  nervous  tissue 
to  institute  narcosis,  can  again  be  replenished  in  so  short  a  time. 

While  no  definite  theory  of  narcosis  has  been  formed  to  supplant 
the  preceding,  some  interesting  data  have  been  gathered  which  partly 
explain  the  anesthesia.     Thus,  it  has  been  shown   by   Meyer^   and 

^  Die  sogenannte  Hypnose  der  Tiere,  Jena,  1898. 

2  Uber  die  Wirkung  des  Schwefelathers,  1847. 

3  .\rchiv  fur  Exp.  Path,  und  Pharm.,  vi,  1901,  12. 


726  THE    CEREBELLUM 

Overton^  that  the  narcosis  depends  upon  the  solubihty  of  the  narcotic 
agent  in  fats  and  oils.  In  general,  those  substances  act  as  narcotics 
which  are  more  readily  soluble  in  fat-like  media  than  in  water;  in 
fact,  the  power  of  these  agents  is  directly  proportional  to  their  fat 
solubility.  It  has  also  been  established  that  their  action  is  produced 
by  the  free  molecule  and  not  by  the  products  of  their  decomposition. 
Thus,  the  esters  of  the  fatty  acids  narcotize  only  while  they  remain 
unsaponified.  They  lose  this  property  as  soon  as  they  are  spHt 
into  the  corresponding  alcohol  and  fatty  acid.  This  characteristic 
effect  upon  the  nervous  system  is  made  possible  by  their  going  into 
solution  with  the  fat-like  constituents  of  this  tissue,  the  lipoids. 
As  nervous  tissue  contains  an  especially  large  amount  of  these  sub- 
stances, the  narcotics  must  be  capable  of  entering  this  tissue  much 
more  easily  than  others. 

Having  shown  that  the  accumulation  of  the  narcotics  in  the  nervous 
tissue  is  due  to  their  solution-affinity  for  the  lipoids,  we  may  go  one 
step  farther  and  state  that  the  essential  cause  of  narcotic  action  is  the 
solution-reaction  between  them  and  the  lipoids.  In  this  connection, 
it  might  be  mentioned  that  Hober^  has  found  the  colloidal  state  of 
the  cells  to  be  changed  during  narcosis,  and  that  Winterstein^  has 
proved  that  narcotized  tissue  ceases  to  take  up  oxygen  even  when 
made  to  produce  work  in  a  superfluity  of  this  gas.  The  evidence  tends 
to  show,  however,  that  while  the  inhibition  of  oxidation  constitutes 
a  factor  in  narcosis,  it  is  not  actually  its  cause. 

^  Studien  liber  die  Narkose,  Jena,  190L 
2  Zeitschr.  fiir  allg.  Physiol.,  xi,  1910,  173. 
» Ibid.,  vi,  1907,  315. 


PART  VI 
THE  SENSE-ORGANS 

SECTION  XX 
SPECIAL  SOMATIC  AND  VISCERAL  RECEPJORS 


CHAPTER  LIX 
CLASSIFICATION  OF  THE  SENSE-ORGANS 

The  Different  Manifestations  of  Energy. — Until  now  we  have  re- 
garded the  central  nervous  system  as  a  mechanism  controlling  our 
various  motor  actions  in  a  way  to  conform  with  the  conditions  existing 
in  our  environment.  As  such  it  occupies  a  position  intermediate 
between  the  different  afferent  and  efferent  paths,  fulfilling  the  function 
of  a  machine  which  converts  or  synthetizes  the  incoming  impulses  into 
motor  responses.  We  have  previously  seen  that  the  efferent  side  of 
this  circuit  is  not  greatly  diversified,  because  all  the  effectors  in  our 
body  are  built  up  either  of  muscle  tissue'or  glandular  tissue.  On  the 
afferent  side,  on  the  other  hand,  we  find  a  decided  multipUcity  in 
structure  to  correspond  with  the  diverse  character  of  the  influences 
to  which  we  may  be  subjected. 

Our  body  is  surrounded  by  a  medium  which  is  teeming  with  mani- 
festations of  energy  in  its  different  forms.  Against  these  the  body 
is  partially  protected  by  a  relatively  impervious  capsular  investment, 
the  skin.  Here  and  there,  however,  this  investment  is  beset  with 
orifices  for  the  admission  of  those  stimuh  which  are  essential  to  our 
life.  These  perforations  really  correspond  to  the  windows  of  a  house 
which  enable  us  to  come  into  functional  relationship  with  the  outside 
world.  This  is  also  true  of  the  lower  animals  and  even  of  those 
forms  which  are  not  in  possession  of  a  nervous  system.  In  the  latter, 
the  different  manifestations  of  energy  are  brought  to  bear  directly 
upon  their  hving  substance,  but  not  in  an  indiscriminate  manner,  be- 
cause, with  the  exception  of  a  few,  these  organisms  are  all  at  least 
partly  protected  against  excessive  stimuh  by  some  sort  of  an  enveloping 
membrane  or  calcareous  shell.  Furthermore,  all  these  organisms  pos- 
sess a  much  more  Umited  range  of  excitation  than  the  higher  forms,  so 
that  they  are  open  to  only  a  few  types  of  stimuh,  principally  to  those 
of  mechanical  and  thermal  origin. 

727 


728  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

Recurring  to  the  analogy  of  the  house  with  the  many  windows,  it 
may  then  be  said  that  these  different  openings  are  beset  with  a  special- 
ized form  of  protoplasm  which,  owing  to  its  chemi co-physical  constitu- 
tion, is  especially  sensitive  to  energy  impressions  from  without,  and  is 
also  modified  in  such  a  way  that  it  can  receive  only  one  particular  kind 
of  stimulus.  In  other  words,  these  sense-organs  or  receptors  show 
individual  differences  which  render  them  more  particularly  adapted  to 
a  certain  type  of  energy  manifestation.  Thus,  the  retina  of  our  eye 
cannot  be  activated  by  sound  waves,  nor  can  the  organ  of  Corti  be 
stimulated  by  the  ethereal  impacts  of  light.  Each  receptor,  therefore, 
is  set  aside  for  only  one  kind  of  stimulus  and  remains  impervious 
to  others  not  specifically  suited  for  it.  It  is  true,  however,  that  in 
most  cases  these  receptors  may  be  subjected  to  non-specific  stimuli 
artificially,  but  the  effects  are  then  quite  different  from  normal. 
Thus,  it  is  possible  to  stimulate  the  retina  either  mechanically  or 
electrically,  in  which  case  visual  sensations  in  the  form  of  phosphenes 
will  be  obtained,  but  these  sensations  are  obviously  very  different  from 
ordinary  light  impressions. 

This  specificity  of  the  different  sense-organs  is  to  be  attributed  to 
the  peculiar  structure  and  composition  of  the  neuroplasm  forming 
them.  Their  function,  however,  is  materially  enhanced  in  many  cases 
by  the  fact  that  the  nervous  terminals  are  amplified  by  certain  acces- 
sory structures  which  tend  to  concentrate  the  stimuli  precisely  upon 
the  receptor  so  as  to  intensify  their  force.  Thus,  we  find  that  the 
essential  receptive  element  of  the  eye  is  the  retina,  while  the  different 
refractive  media  of  this  organ,  together  with  the  iris,  merely  serve  the 
purpose  of  concentrating  the  light  rays  upon  its  most  sensitive  con- 
stituent. The  same  is  true  of  the  organ  of  Corti,  because  the  exter- 
nal ear,  the  eardrum,  and  ossicles  merely  serve  to  increase  the  striking 
force  of  the  sound  waves  and  to  direct  them  to  the  sensitive  epithelium 
in  the  cochlea. 

The  orifices  in  our  integument  in  which  the  different  sense-organs 
are  placed,  form,  so  to  speak,  points  of  least  resistance  through  which 
the  energy  manifestations  in  space  may  reach  the  interior  of  our  body. 
But,  as  has  been  stated  above,  each  gateway  permits  of  the  entrance 
of  only  one  particular  kind  of  impact,  because  its  resistance  toward  the 
others  is  heightened  sufficiently  to  exclude  them.  In  general,  it 
may  be  said  that  we  are  subject  to  two  types  of  energies,  namely,  the 
vibratory  and  the  chemical,  which  in  turn  have  been  classified  by 
Herrick^  as  follows: 

A.   Vibratory  Energy. 

1.  Mechanical  impacts  received  by  the  tactile  corpuscles  of  the  skin  at  a  rate 
of  as  high  as  1552  vibrations  in  a  second. 

2.  Slow  vibrations  in  material  media  received  by  the  organ  of  Corti,  and  sub- 
jectively perceived  as  sound.  The  human  ear  is  activated  by  vibrations  varying 
between  30  and  30,000  in  a  second.  In  some  cases,  however,  this  range  may  be 
extended  to  40,000  and  50,000  vibrations  per  second. 

1  An  introduction  to  Neurology,  Saunders  Co.,  Philadelphia,  1915. 


CLASSIFICATION    OF   THE    SENSE    ORGANS  729 

3.  Rapid  vibrations  in  dhcr,  or  waves  in  iiiunatcrial  modia,  received  by  the 
temperature  corpuscles  of  the  skin  (heat-rays)  and  the  retime  of  the  eyes  (hght- 
rays).  These  vil)rations,  however,  also  include  some  to  which  we  are  absolutely 
insensitive  or  which  can  only  be  perceived  with  the  help  of  certain  accessory  means. 
The  Hertzian  electrical  waves  attain  a  vibratory  frequency  of  3000  billions  per 
second,  the  ultra-violet  rays  one  of  5,100,000  billions  per  second,  and  the  Roentgen- 
rays  one  of  6,000,000,006  billions  per  second.  In  between  these  two  extremes 
lies  the  receptive  scala  of  man.  Thus,  we  find  that  our  retina  is  capalile  of  recei\dng 
impacts,  the  vibrations  of  which  vary  lietween  about  400,000  and  800,000  billions 
per  second.  This  range  covers  the  solar  spectrum.  Between  these  vibrations  and 
those  attaining  a  frequencj'^  of  3000  billions  per  second,  lies  the  realm  of  the  radiant 
heat  which  stimulates  the  temperature  receptors  of  our  skin. 
B.  Chemical  Energy. 

The  different  chemical  impacts  to  which  we  may  be  exposed,  are  received  in  a 
relatively  imperfect  manner.  The  organ  of  smell  covers  a  much  wider  range  than 
the  organ  of  taste;  in  fact,  the  latter  gives  rise  to  only  four  fundamental  sensations, 
namely,  sweet,  bitter,  salty  and  sour. 

Classification  of  the  Sense-organs. — The  foregoing  discussion 
shows  first  of  all  that  under  ordinary  conditions  only  a  Hmited  number 
of  the  energies  developed  in  space,  are  made  accessible  to  man.  This 
statement,  however,  is  not  meant  to  imply  that  the  equipment  of  other 
animals  is  as  good  as  that  of  man;  in  fact,  the  chances  are  that  it  is 
not,  for  the  reason  that  the  human  nervous  system  attains  the  most 
perfect  all  around  development.  It  cannot  be  doubted,  however,  that 
the  sensory  mechanisms  of  a  particular  group  of  animals  may  be  more 
fully  developed  along  certain  lines  than  those  of  others.  This  is  especi- 
ally true  of  the  olfactory  apparatus;  but  may  also  be  true,  for  example, 
of  the  \dsual  and  auditory  mechanisms  of  the  birds  as  against  those 
of  man.  At  all  events,  provision  has  been  made  in  each  case  to  equip 
the  different  animals  more  especially  mth  those  sense-organs  which 
are  of  greatest  practical  use  to  them. 

Man  has  been  placed  in  a  position  to  analyze  the  energy  manifes- 
tations in  space  by  means  of  five  senses,  i.e.,  he  is  able  to  bring  five 
different  means  to  bear  upon  the  forces  of  nature  for  purposes  of 
orientation.  The  sense-organs  concerned  in  this  analysis,  are  com- 
monly said  to  be  the  eyes,  ears,  nose,  tongue  and  skin.  In  agreement 
with  this  classification  the  layman  recognizes  five  senses,  namely,  sight, 
hearing,  smell,  taste  and  touch.  One  discrepancy,  however,  must 
occur  to  us  immediately,  namely,  that  this  classification  does  not  em- 
brace the  large  number  of  different  receptors  which  are  concerned  with 
the  reception  of  stimuH  arising  in  the  interior  of  our  body.  In  the 
second  place,  attention  should  be  called  to  the  fact  that  several  of  the 
original  five  senses  are  really  composite  in  type.  Obviously,  the  ear 
contains  not  only  the  organ  of  hearing,  but  also  separate  receptors  for 
the  static  and  djmamic  senses.  Quite  sunilarly,  the  skin  is  not  only 
concerned  with  touch,  but  also  mediates  the  sensations  of  pressure, 
pain,  and  temperature.  To  be  brief,  it  vnW  be  brought  out  later  on 
that  there  are  in  reality  more  than  twenty  different  receptors  in  our 
body.^ 

lOhrwall,  Skand.  Archiv  fiir  Physiol.,  xi,  1901. 


730  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

The  preceding  discussion  must  have  shown  that  the  central  nervous 
system  really  performs  two  important  functions,  namely,  to  control 
the  activities  of  the  different  tissues  and  organs,  and  secondly,  to  bring 
the  latter  into  a  proper  relation  with  the  outside  world.  Since  this 
control  is  effected  with  the  help  of  two  different  groups  of  nervous 
structures,  the  central  nervous  system  may  be  divided  theoretically  into 
a  visceral  and  a  somatic  part.  For  the  same  reason,  the  sense-organs 
may  be  classified  as  visceral  and  somatic,  the  former  having  to  do  with 
the  sensations  arising  within  our  body,  and  the  latter  with  those  pro- 
duced by  the  energies  in  space.  It  should  be  noted,  however,  that 
these  groups  of  organs  are  not  functionally  isolated  from  one  another, 
but  are  closely  correlated  so  that  they  can  always  influence  one  another. 
Thus,  we  find  that  a  visceral  sensation  may  give  rise  to  a  somatic 
response,  and  vice  versa.  This  classification  has  been  made  more  em- 
bracing by  Sherrington,^  who  divides  the  somatic  group  of  receptors 
into  exteroceptors  and  proprioceptors,  and  the  visceral  group  into 
general  and  special  interoceptors,  as  follows: 

A.  Somatic  receptors,  having  to  do  with  the  orientation  of  the  animal  toward  its 
environment. 

1.  Exteroceptors,  are  stimulated  under  ordinary  conditions  by  outside  forces 
The}'  embrace  the  end-organs  for:  (a)  touch  and  pressure,  (6)  pain,  (c)  heat  and 
cold,  (d)  general  chemical  sensibihty,  (e)  hearing,  and  (/)  vision. 

2.  Proprioceptors,  are  situated  in  the  muscles,  tendons  and  joints  and  are  con- 
cerned with  the  production  of  the  muscle-sense.  To  this  group  also  belong  the 
end-organs  which  have  to  do  with  the  sensations  of  equilibrium,  namely,  the  oto- 
lithic cavities  (static  sense)  and  the  semicircular  canals  (dynamic  sense). 

B.  Visceral  receptors,  are  concerned  with  the  stimulations  arising  within  the  body, 
principally  in  connection  with  digestion,  secretion,  the  action  of  the  heart,  and 
other  functions. 

L  General  interoceptors,  embrace  the  end-organs,  mediating  the  sensations  of 
hunger,  thirst,  nausea,  respiratory  and  circulatory  sensations,  sexual  sensations, 
visceral  pain,  and  others. 

2.  Special  interoceptors,  consist  of  the  end-organs  for  taste  and  smell.  Both 
are  excited  by  chemical  stimuli  and  while  both  are  typical  interoceptors  to  begin 
with,  the  organ  of  smell  eventually  becomes  more  closely  associated  with  outside 
conditions.  2  In  the  amphibians  and  alhed  animals  it  is  really  the  chief  extero- 
ceptor,  although  its  more  primitive  interoceptive  qualities  are  still  in  evidence. 

Like  the  animals,  plants  are  also  exposed  to  varying  conditions  in  the  environ- 
ment and  are  in  possession  of  intensifying  receiving  organs.  As  such  may  be 
classified  the  bristles  upon  the  leaf  of  Dionsea  as  well  as  those  upon  the  stems  and 
leaves  of  Mimosa  pudica. 

The  Doctrine  of  the  Specific  Nerve  Energies. — It  is  by  no  means 
difl&cult  to  see  that  the  energy  manifestations  give  rise  to  very  specific 
sensations  and  reactions.  The  question  then  arises,  whether  this 
specificity  is  due  to  peculiarities  in  the  energy  or  to  peculiarities  in  the 
structure  of  the  sense-organs.  Johannes  von  Mliller  favors  the  second 
view  without,  however,  positively  referring  it  to  any  particular  segment 
of  the  neuron.     In  more  recent  years  physiologists  have  gone  a  step 

^The  Intergrative  Action  of  the  Nervous  System,  New  York,  1906. 
2  C.  J.  Herrick,  Jour.  Comp.  Neurol.,  xciii,  1908,  157. 


CLASSIFICATION    OF    THE    SENSE    ORGANS  731 

farther  and  have  rather  generally  concluded  that  the  specific  quality  of 
a  sensation  in  consciousness  is  dependent  upon  the  center  and  not  upon 
the  contlucting  path  nor  upon  its  receiving  organ.  The  second  pos- 
sibility may,  of  course,  be  justly  ruled  out,  because  nerve  fibers  are  con- 
ductile  elements  and  nothing  more  than  that.  The  third  possibility 
cannot  be  excluded  so  easily,  because  the  sense-organs  exhibit  particu- 
lar structural  details  which  render  them  especially  adapted  for  the 
reception  of  single  kinds  of  energy  manifestations.  On  the  other  hand,  it 
is  evident  that  this  specificity  of  the  end-organ  could  not  be  of  any  avail, 
were  it  not  for  the  fact  that  the  center  possesses  a  similar  specificity. 
Besides,  since  the  latter  is  commonly  regarded  as  the  controlling  factor 
of  all  nervous  processes,  it  may  also  be  considered  as  the  determining 
agent  of  these  impressions  in  consciousness.  Consequently,  the  end- 
organ  merely  enables  a  particular  stimulus  to  enter,  and  determines 
whether  or  no  the  latter  should  become  effective  centrally.  Thus,  if 
it  were  possible  to  cross  the  optic  and  auditory  nerves,  so  as  to  connect 
the  retina  with  the  auditory  center  and  the  organ  of  Corti  with  the 
visual  center,  we  would  hear  pictures  and  see  sounds. 

The  experimental  evidence  which  might  be  mentioned  in  favor  of 
the  doctrine  of  specific  nerve  energy,  includes  such  positive  data  as 
the  following: 

(a)  An  impression  in  consciousness  is  often  obtained  without  the  help  of  the 
sense-organ  and  conducting  path.  For  example,  subjective  sensations  of  light  are 
frequently  gotten  in  a  perfectly  dark  room  and  when  the  eyes  are  closed.  Ringing 
in  the  ears  is  another  common  subjective  phenomenon.  Central  causes  must  also 
be  held  responsible  for  the  multitude  of  concepts  obtained  during  dreams  and  in 
consequence  of  pathological  conditions,  such  as  arise  during  hysteria  and  states  of 
excessive  sensitiveness  of  the  nervous  system. 

(b)  The  different  sense-organs  may  also  be  activated  by  stimuli  other  than 
those  ordinarily  received  by  them.  Thus,  sensations  of  light  may  also  be  produced 
by  exerting  a  slight  pressure  upon  the  eyeball  or  by  passing  an  electrical  current 
through  it.  Quite  similarly,  an  electrical  current  directed  through  the  tongue, 
evokes  sensations  of  taste,  but  sensations  of  touch,  when  applied  to  the  skin.  A 
tuning  fork  made  to  vibrate  in  the  vicinity  of  the  ears,  gives  rise  to  sound  sensations, 
and  when  allowed  to  beat  against  the  skin,  to  the  peculiar  tactile  impression 
known  as  tickling. 

(c)  Very  similar  effects  may  be  obtained  by  the  stimulation  of  the  nerve  fibers 
leading  away  from  these  sense-organs.  Thus,  the  cutting  of  the  optic  nerve  evokes 
flashes  of  light,  while  the  excitation  of  the  chorda  tympani  during  its  course  through 
the  tj^mpanic  cavity  gives  rise  to  sensations  of  taste  upon  the  tip  of  the  tongue. 
In  many  cases,  these  diverse  sensations  are  elicited  in  consequence  of  tumors, 
exudations,  and  hyperemic  conditions  in  the  course  of  sensory  nerves. 

(d)  Sensations  may  be  dissociated.  A  degree  of  pressure  may  be  brought  to 
bear  upon  the  skin  which  destroys  the  sensation  of  touch  and  temperature,  but  not 
that  of  pain.  This  preservation  of  one  particular  cutaneous  impression  to  the  ex- 
clusion of  others,  is  frequently  observed  in  the  beginning  stages  of  degeneration  and 
regeneration  following  the  division  of  peripheral  nerves.  This  dissociation  may 
also  be  effected  by  chemical  means,  for  example,  the  taste  of  bitter  may  be  destroyed 
by  cocain  and  that  of  sweet  by  gymnemna  sylvestris. 

The  Modality  of  a  Sensation. — It  is  a  matter  of  common  experience 
that  the  different  sensory  impressions  are  not  referred  to  the  brain  at 


732  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

all,  but  are  projected  to  the  sense-organ  in  which  they  have  arisen  and 
even  beyond  the  latter  to  the  area  in  space  from  which  they  have  been 
derived.  Thus,  the  sensations  of  touch  are  referred  to  the  surface  of 
the  body  and  those  of  taste  to  the  tongue  and  mouth.  Quite  similarly, 
the  sensations  of  sight  and  hearing  are  alwaj^s  interpreted  as  having 
been  received  from  a  particular  realm  in  space.  It  must  be  evident, 
therefore,  that  a  sensation  cannot  be  regarded  as  a  definite  cortical 
concept,  because  since  judgment  enters  this  act,  which  always  com- 
prises other  activities,  the  resultant  impression  is  really  the  symbolical 
picture  of  the  conditions  mediated  from  without. 

Each  sensation,  however,  is  symbolized  independently  of  the  others, 
because  the  sensations  of  light  are  distinct  from  those  of  taste,  smell, 
hearing  and  touch.  This  implies  that  every  one  of  them  possesses  a 
definite  quality  or  modality  which  we  have  learned  to  recognize  in 
the  course  of  time.  In  spite  of  this  fact,  however,  it  would  be  quite 
impossible  for  us  to  compare  these  modalities  with  one  another.  To 
be  sure,  we  clearly  understand  what  is  meant  by  the  sensations  of  bit- 
ter, an  intense  hght,  a  low  pitched  sound,  and  other  impressions,  al- 
though we  are  unable  to  estimate  the  precise  character  of  these  quaUties 
so  as  to  be  able  to  say,  for  example,  that  this  sound  is  louder  than  this 
taste  is  sweet.  Consequently,  each  sensation  possesses  a  modality 
which  is  absolutely  specific  to  it.  Sensations  mediated  by  one  and 
the  same  sense-organ,  however,  we  are  able  to  rate  in  a  quantitative 
manner,  because  we  clearly  recognize  differences  in  the  pitch  of  the 
sounds  and  in  the  intensity  of  the  light,  and  are  able  to  tell  that  the 
sweet  taste  of  a  given  substance  is  more  pronounced  than  that  of 
another. 

Fatigue  and  Adaptation. — While  the  different  receptors  may  be 
activated  by  stimuli  of  a  non-specific  character,  they  are  usually  open 
to  those  kinds  of  impacts  only  for  which  they  are  especially  con- 
structed. It  may  be  said,  therefore,  that  the  sense-organs  form 
channels  of  least  resistance  through  which  appropriate  stimuli  are 
allowed  to  pass  with  the  least  possible  loss  of  energy  to  them.  Be- 
ginning with  this  minimal  or  threshold  value,  an  increased  strength  of 
stimulation  always  gives  rise  to  a  more  intense  sensation,  but  an  upper 
limit  is  finally  reached  beyond  which  a  further  augmentation  is  impos- 
sible. This  augmentation,  however,  is  not  always  proportional  to  the 
intensity  of  the  stimulus,  because  an  undue  strength  or  duration  of  the 
stimulation  invariably  results  in  a  fatigue  which  seems  to  affect  pri- 
marily the  recipient  centers.  It  is  also  evident  that  the  sense-organs 
are  much  more  receptive  toward  repeated  stimuli  of  minimal  strength 
than  toward  single  stimuli  of  maximal  strength.  In  addition,  they 
possess  the  power  of  adaptation,  which  in  many  cases  may  be  employed 
to  intensify  the  primary  sensation.  Thus,  we  speak  of  a  dark-adapted 
eye,  i.e.,  an  eye  which  is  at  first  kept  in  complete  darkness  so  that 
it  may  later  on  be  activated  by  much  lower  intensities  of  light  than  are 
ordinarily  required  to  stimulate  one  which  has  just  been  exposed  to  light. 


CLASSIFICATION    OF   THE    SENSE    ORGANS  733 

Weber's  Law. — While  it  is  true  that  the  intensity  of  a  sensation 
increases  with  the  strength  of  the  stimulus,  the  former  does  not  pre- 
serve a  direct  relationship  to  the  latter.  Clearly,  the  different  sense- 
organs  are  adjusted  in  such  a  way  that  they  can  receive  their  specific 
stimuli  with  the  greatest  possible  ease;  in  other  words,  their  threshold 
value  is  low.  This  implies  that  the  maximum  value  of  a  sensation  is 
attained  very  quickly  and  that  stimuli  of  greater  intensity  do  not  aug- 
ment the  primary  impression  in  any  appreciable  measure;  in  fact,  their 
tendency  is  to  produce  fatigue.  Now,  while  it  is  a  relatively  simple 
matter  to  determine  the  strength  of  the  stimulus  which  is  required  to 
evoke  a  certain  sensation,  it  is  difficult  to  obtain  comparative  values 
of  sensations,  whether  of  the  same  or  of  different  character.  This  in- 
ability on  our  part  of  rating  sensations  in  an  absolute  quantitative  man- 
ner forces  us  to  rely  solely  upon  our  power  of  perceiving  slight  differences 
in  them.  One  way  of  doing  this  is  to  ascertain  how  greatly  a  stimulus 
must  be  increased  in  order  to  give  rise  to  an  appreciable  sensation  of 
difference.  Consequently,  the  only  two  means  at  our  disposal  for  rating 
sensations  in  a  quantitative  way  are  first,  the  determination  of  the 
threshold  value  of  the  stimulus  required  to  elicit  a  certain  sensation,  and 
secondl}'^,  the  determination  of  the  increase  in  the  strength  of  the 
stimulus  necessary  to  produce  a  distinct  difference  in  the  sensation. 

E.  H.  Weber,  ^  who  first  attempted  to  obtain  such  values,  made  the 
observation  that  the  stimulus  necessary  to  cause  a  sensation  of  differ- 
ence, is  proportional  to  the  intensity  of  the  stimulus  then  acting,  i.e., 
it  forms  a  fractional  increment  of  the  latter.  Subsequent  determina- 
tions, however,  have  shown  that  this  law  holds  true  only  for  stimuH  of 
moderate  intensity.  Thus,  if  a  weight  of  30  grams  is  placed  upon 
the  tip  of  the  index  finger  of  a  hand  supported  at  the  wrist,  and  is 
properlj'  adjudged  by  means  of  the  muscle-sense,  an  additional  weight 
of  1  gram  must  be  added  to  or  subtracted  from  these  original  30  grams 
before  a  distinct  difference  in  this  sensation  will  be  obtained.  If  this 
test  is  now  repeated  with  a  primary  weight  of  60  grams,  it  will  be  found 
that  2  grams  are  required  in  order  to  produce  a  sensation  of  difference, 
and  with  90  grams  an  additional  weight  of  3  grams,  and  so  on,  until 
the  physiological  limit  is  reached  at  about  1000  grams.  In  this  par- 
ticular case,  therefore,  the  increment  is  3=io  of  tlie  original  stimulus. 
Naturally,  this  law  holds  true  for  any  quality  of  stimulus,  provided 
that  the  latter  is  of  moderate  intensity.  For  sounds  the  appreciation 
difference  is  ^,  and  for  light  ^{20  of  the  original  stimulus.  Conse- 
quently, the  eye  is  the  most  sensitive  organ. 

Fechner's  Psychophysical  Law. — The  attempt  has  been  made  by 
Fechner^  to  generalize  the  preceding  law  and  to  place  it  upon  an  ac- 
curate quantitative  basis.  It  is  stated  that  the  sensations  show  the 
same  relationship  to  the  stimuli  as  the  logarithms  to  their  numerals. 
Fechner's  law,  therefore,  may  be  expressed  by  the  formula  S  =  C 

'  Wagner's  Handworterbuch  der  Physiol.,  iii,  1846,  481. 
^Elemente  der  Psychophy.sik;,  Leipzig,  1860. 


734 


SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 


log  R,  in  which  S  indicates  the  sensation,  R  the  stimulus  and  C  the 
constant  represented  bj"  the  difference  in  the  sensation.  But  this 
conception,  that  the  sensation  is  proportional  to  the  logarithm  of 
the  stimulus,  must  meet  with  serious  objections,  because  it  has  been 
proved  that  Weber's  law  is  not  applicable  to  stimuli  of  low  and  high 
intensity.  In  addition,  Fechner  has  assumed  that  the  smallest 
appreciable  increase  in  the  sensation  must  always  remain  the  same, 
i.e.,  the  difference  in  the  sensation  obtained  when  1  gram  is  added  to  30 
grams,  must  be  the  same  as  that  evoked  by  the  addition  of  2  grams 
to  60  grams.  Physiological  observation  has  proved  this  assumption  to 
be  incorrect,  and  hence,  we  may  justly  advocate  the  view  of  James, 
that  the  attempt  to  measure  sensations  with  mathematical  precision, 
is  a  mere  speculation. 


CHAPTER  LX 

THE  SENSES  OF  PRESSURE  OR  TOUCH,  PAIN,  AND 
TEMPERATURE 

The  Structure  of  Cutaneous  Receptors. — The  integument  of  our 
body  is  permeated  by  two  sets  of  nerve-plexuses,  one  of  which  is  situ- 
ated in  the  panniculus  adiposus  and  the  other 
in  the  stratum  subpapillare.  Both  ramifi- 
cations give  rise  to  fibrils  which  terminate 
in  peculiar  end-organs  in  almost  all  layers 
of  the  skin.  The  most  common  of  these 
consist  of  medullated  fibers  from  the  dermal 
plexus  which  give  off  branches  and  soon  lose 
their  medullar}-  sheath.  The  latter  pierce 
the  epidermis  and  then  form  arborizations 
among  the  cells  of  the  Malpighian  layer. 
The  different  fibers  end  bluntly  or  are  ex- 
panded into  distinct  sensory  plates.  Phylo- 
genetically  considered  the  latter  formation  is 
the  more  recent. 

The  corpuscles  of  Meissner  (1852)  are  found  in 

*  the  papillary  and  subpapillarj'  layers  of  the  skin. 

FiQ.  3  61. — Tactile  Cor-   They  acquire  a  length  of  from  40-100/x  and  exhibit 

puscLE  WITHIN  A  Papilla  OF   an  oval  or  round-elliptical  outline.     Their  outer  zone 

THE  Skin  OF  THE  Hand,  Stained   consists  of  connective  tissue  lamella}  which  invest  a 

WITH  Chlorid  OF  Gold.    (Ran-   ^^^^  ^^  reticular  tissue  through  which  one,  two,  or 

several  non-medullated  nerve  fibers  wind  their  way 

n  Two  nerve-fibers  passing   g  .rallv  to  the  tip  of  this  structure.     A  very  similar 

to  the  corpuscle;  a,  o,  varicose  "  .    .  .     i  i       .1      /~i   i    ■  at 

ramifications  of  the  axis-cylin-   arrangement  IS  presented  by  the  Golgi-Mazzoni  cor- 

ders  within  the  corpuscle.  P^scle  (1880)  as  well  as  by  that  described  by  \  ater 

and  Paccini  (1840).  The  latter  are  small  oval 
bodies  which  attain  a  length  of  from  2-4.5  mm.  and  a  breadth  of  1-2  mm.  Their 
outer  zone  consists  of  concentric  lamellae,  while  their  core  is  penetrated  bj^  a  nerve- 


THE  SENSES  OF  PRESSURE  OR  TOUCH 


735 


fiber  which  may  be  sinfilo  or  split  up  into  a  delicate  ramification.  These  end-organs 
are  very  iuimumous  in  the  .subcutaneous  connective  tissue.  The  corpuscle  of  Herbst 
which  is  chiefly  found  in  birds,  is  somewhat  smaller,  but  very  similar  in  structure 
to  the  precodinp;.  Another  cutaneous  receptor  has  been  described  by  Krause  (1860). 
It  is  globular  in  shape  and  its  central  region  is  taken  up  by  the  arborization  of  the 
nerve  fiber.  ]<]qually  characteristic  and  suggestive  of  their  function  are  the  corpus- 
cles of  Grandry  and  Merkel.  They  consist  of  two  or  several  hemispherical  (u-lls  with 
flattened  surfaces,  between  which  the  nerve  fiber  is  expanded.  Th(;ir  luught 
measures  15/i  and  their  breadth  50^.  The  composite  type  of  these  corpuscles  is 
present  in  great  numbers  in  the  skin  of  the  bill  and  tongue  of  birds.  Several 
different  types  of  endings  have  been  found  around  and  in  the  immediate  vicinity 
of  the  roots  of  hairs. 


Fig. 


362. — Paccinian  Corpuscles  from  the  Peritoneum  of  a  Cat. 
Bohm-Davidoff-Huber' s  Histology.) 


(After  Sola,  from 


Methods  Used  to  Evoke  Tactile  Sensations. — The  skin  is  exposed 
to  influences  which  are  capable  of  eliciting  several  kinds  of  sensations, 
namely,  pressure,  touch,  pain,  cold,  warmth,  tickling,  and  others  of  a 
more  composite  type.  The  sensations  of  pressure  and  touch  are  depen- 
dent upon  mechanical  stimuli  and  find  their  origin  in  a  displacement 
of  the  surface  layers  of  the  skin.^  They  represent  sensations  caused  by 
different  grades  of  the  same  mechanical  impact,  but  the  displacement 
need  not  take  place  in  an  inward  direction  but  may  also  result  in 
consequence  of  pull  upon  the  surface.  In  the  former  case  we  obtain 
a  positive  and  in  the  latter  a  negative  imprint. 

■  The  tactile  sensations  are  usually  tested  by  means  of  an  instrument, 
which  is  known  as  an  esthesiometer.  In  its  simplest  form  it  con- 
sists of  a  hair  or  fiber  of  glass-wool  attached  to  a  handle,  the  tip  of  which 

1  Frey  and  Kiesow,  Zeitschr.  fiir  Psych,  und  Physiol,  der  Sinnesorgane,  xx, 
1899. 


736 


SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 


is  pressed  upon  the  skin  with  a  force  sufficient  to  eHcit  different  in- 
tensities of  tactile  impressions.     This  method  permits  of  the  deter- 
mination of  the  acuity  of  these  sen- 
sations  as  well    as   of   our  ability  to 
localize  them  with  accuracy.      Esthes- 
iometers  are  also  in  use  which  possess 
two    points    of    contact    adjusted    at 
varying  distances  from  one  another. 
This  arrangement  allows  us  to  deter- 
a  mine  how  far  these  points  must  be 
separated  from  one  another  in  order 
./  to  give  rise  to  two  distinct  sensations. 
Our  ability  to  tell  whether  a  tactile 
stimulus  is  single  or  double,  is  known 
as  tactile  discrimination. 

Tactile  Acuity,  Localization  and 
Discrimination. — We  have  seen  that 
the  adequate  stimulus  for  sensations 
of  touch  is  a  mechanical  impact  which 
causes  a  deformity  of  the  surface  of 
the  skin  and  thus  activates  the  sen- 
sory nerve-endings  contained  therein. 
This  activation,  however,  is  accom- 
plished under  normal  condition  with 
the  help  of  certain  adjuncts  consist- 
ing in  peculiar  capsular  investments 
of  the  terminals  of  the  sensory  nerve 
fiber.  Thus,  we  find  that  the  threshold  value  of  a  stimulus  apphed 
to   the   tactile   capsule,   is  very  much   lower  than  that  required  to 


Fig.  363. — Herbst  Corpuscles  of 
Duck. 

n,  Medullated  nerve-fibre;  a,  its 
axis-cylinder,  terminating  in  an  en- 
largement at  end  of  core;  c,  nuclei  of 
cells  of  core;  t,  nuclei  of  cells  of  outer 
tunica;  t',  inner  tunica  (Sobotta)  X 
380  diameters. 


Fig.  3G4. — Krause's  Corpuscle.     A  and  B,  Genital  Corpt'scles  from  the  Clitoris  of 
THE  Rabbit  (Izquierdo) ;  C,  from  the  Human  Clitoris.      (W.  Krause.) 

elicit  a  sensation  from  the  nerve  fiber  itself.     It  is  evident,  there- 
fore, that  the  skin  is  in  possession  of  what  might  be  termed  tactile 


THE    SENSES    OF    PRESSURE    OR    TOUCH 


737 


points,    but   cxperimcntiition    has  shown  that  those    points  are  not 
evenly  distributed   tliroughout  the  skin,  but  are  more  numerous  and 


n 

Fig.  365.  Fig.  366. 

Fig.  365. — Corpuscles  of  Grandry  from  the  Duck's  Tongue.     (Izquierdo.) 

A,  compound  of  three  cells,  with  two  interposed  discs,  into  which  the  axis-cylinder 
of  the  nerve,  n,  is  observed  to  pass;  in  B  there  is  but  one  tactile  disc  enclosed  between 
two  tactile  cells. 

Fig.  366. — Gr.'OJdry  Corpuscle  ix  Tr.^.n'sverse  Section.     (After  Dogiel.) 

more   sensitive   in   some   regions  of  the  integument  than  in  others. 


Fig.  367. — Sensory  NER^•E  Terminating  in  Arborizations  Around  the  Ends  of  Mus- 
cle-fibers.     (Ceccherelli.) 

Their   total   number   has   been  estimated  at  500,000,  excluding  the 
region  of  the  head.     Upon  the  back  of  the  leg,  1.0  sq.  cm.  of  the  skin 

47 


738 


SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 


is  said  to  contain  about  15  of  these  tactile  receptors. '^  The  succeed- 
ing table  shows  how  great  a  pressure  must  be  brought  to  bear  upon 
different  regions  of  the  skin  in  order  to  evoke  minimal  sensations;  the 
degree  of  pressure  being  indicated  here  in  grams  per  square  millimeter 
of  area: 


Fig.  368. — Cold  and  Hot  Spots  from  the  Anterior  Surface  of  the  Forearm. 
a,  Cold  spots.     6,  Hot  spots.     The  dark  parts  are  the  most  sensitive,  the  hatched 
the  medium,  the  dotted  the  feebly,  and  the  vacant  spaces  the  non-sensitive.     (Landois 
and  Stirling.) 

Tongue  and  nose 2 

Lips 2.5 

Finger-tip  and  forehead 3 

Back  of  the  finger 5 

Palm  of  the  hand,  arm  and  thigh 7 

Forearm 8 

Back  of  the  hand 12 

Back  of  the  leg  and  shoulder 16 

Abdomen 26 

Sole  of  the  foot 28 

Back  of  the  forearm 33 

Gluteal  region 48 

The  acuity  of  the  discriminating  sense  also  varies  in  different  regions  of  the 
skin,  as  may  be  gathered  from  the  succeeding  table : 

Tip  of  tongue 1.1  mm. 

Palm  of  the  last  phalanx  of  the  finger 2.2  mm. 

Palm  of  the  second  phalanx  of  the  finger 4.4  mm. 

Tip  of  the  nose 6.6  mm. 

Back  of  the  second  phalanx 11.1  mm. 

Back  of  the  hand 29 . 8  mm. 

Forearm 39 . 6  mm. 

Sternum 44 . 0  mm. 

Region  along  spine 54 . 0  mm. 

Middle  of  the  back 67 . 0  mm. 


*  Vitreg,  Ber.  der  sachs.  Gesellsch.  der  Wissensch. 
Wundt's  phil.  Studien,  xix,  1902. 


xxiii,  1896,  and  Kiesow, 


THE  SENSES  OF  PRESSURE  OR  TOUCH  739 

It  will  bo  scon  that  the  tonsuo,  tips  of  tho  fingors  and  nose  are 
the  most  sensitive  regions.  Other  areas  are  frequently  beset  with 
hairs  which  tend  to  increase  the  intensity  of  the  excitation  in  a  per- 
fectly mechanical  way,  l)ccauso  they  act  as  levers  upon  the  tactile 
corpuscles  l.ying  in  the  immediate  vicinity  of  th(!ir  roots.  Moreover, 
the  pressing  down  of  their  shafts  tends  to  augment  the  displacement 
of  the  surface  layers.  Hairs,  therefore,  tend  to  lower  the  threshold 
value  of  the  excitation  and  to  impart  to  the  latter  a  peculiar  quality 
which  renders  stroking  movements  and  all  laterally  applied  impacts 
especially  effective.  Variations  in  tactile  acuity  may  be  produced 
by  increasing  or  decreasing  the  blood-supply,  by  the  administration 
of  such  drugs  as  morphin,  strychnin  and  alcohol,  and  by  training. 
Thus,  we  find  that  the  tactile  sense  is  especially  keen  in  blind  persons 
and  in  type-setters. 

Touch  Illusions. — Weber  conceived  the  skin  as  being  subdivided 
into  a  number  of  touch  circles  or,  as  Hermann  has  called  them,  touch 
areas,  within  the  boundaries  of  which  the  two  points  of  an  esthesiometer 
are  perceived  as  one.  The  size  of  these  fields  differs,  a  fact  which  may 
readily  be  deduced  from  the  preceding  table.  It  was  assumed  further 
that  every  one  of  these  touch  points  is  represented  in  consciousness 
by  a  local  sign  or  quality  which,  however,  does  not  retain  a  local 
character  but  is  projected  outward  to  the  area  of  the  skin  stimulated. 
Furthermore,  this  sensation  is  not  perceived  as  a  rule  in  the  form  of  a 
simple  deformation  of  the  surface  of  the  skin,  but  as  an  actual  re- 
production of  the  object.  In  many  instances,  this  projection  is  even 
extended  to  a  point  beyond  the  skin.  Thus,  we  find  that  the  peculiar 
grating  sensation  produced  when  cutting  into  bone,  is  not  referred 
to  the  fingers,  but  to  the  knife  itself. 

Our  associations  pertaining  to  tactile  sensations,  may  easily  be 
upset  by  subjecting  them  to  unusual  conditions.  This  fact  is 
typically  illustrated  by  an  experiment  first  described  by  Aristotle.^ 
If  the  index  and  middle  fingers  of  the  right  hand  are  crossed,  a  marble 
rolled  around  between  their  tips  in  the  palm  of  the  left  hand  will  appear 
as  two.  This  illusion  is  due  to  the  fact  that  the  crossing  of  the  fingers 
brings  two  sets  of  tactile  corpuscles  together  which  are  ordinarily 
far  removed  from  one  another  and  are  rarely  called  upon  to  act  in 
unison.  Consequently,  the  corpuscles  upon  the  radial  side  of  the 
index  finger,  as  well  as  those  upon  the  ulnar  side  of  the  middle  finger, 
give  rise  to  separate  sensations.  Quite  similarly,  it  has  been  observed 
that  the  tactile  sensations  obtained  from  a  flap  of  the  skin  of  the  fore- 
head which  has  been  turned  downward  to  cover  a  defect  of  the  nose, 
are  at  first  referred  to  the  forehead.  Later  on,  however,  new  judg- 
ments are  formed,  which  enable  the  individual  finally  to  localize  these 
sensations  correctly.  If  the  tip  of  the  nose  is  palpated  between  the 
tips  of  two  crossed  fingers,  it  appears  as  two. 

1  Metaphysics,  iii,  Chapter  6. 


740  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

The  Sense  of  Pain. — Uncomfortable  and  painful  sensations  may  be 
mediated  by  any  sense-organ  and  even  if  the  intensity  of  the  stimulus 
is  slight.  This  is  true  particularly  of  obnoxious  odors,  noises,  very  loud 
sounds  and  high  intensities  of  light.  As  commonly  interpreted,  how- 
ever, the  word  pain  refers  to  a  very  definite  sense  quality  which  allows 
of  a  rather  precise  localization,  while  the  painful  sensations  just  alluded 
to,  are  indefinite  and  general  in  their  character.  Pain  is  widely  dis- 
tributed throughout  the  body,  and  is  a  common  phenomenon  even  in 
the  deeper  tissues  and  organs.  The  most  sensitive  part,  however,  is 
the  skin,  as  may  be  gathered  from  the  fact  that  an  incision  in  the 
integument  always  elicits  a  more  intense  pain  than  the  handling  and 
cutting  of  the  deeper  structures.  According  to  Von  Frey,^  more  than 
one  hundred  pain  points  are  allotted  to  each  1  sq.  mm.  of  skin.  It 
also  appears  that  the  visceral  receptors  for  pain  cannot  be  activated 
by  ordinary  mechanical  means.  Thus,  it  is  possible  to  operate  upon 
the  stomach  and  intestine  without  causing  an  acute  sensation  of  pain, 
while  inflammatory  reactions  in  these  organs  or  their  distention  by 
gases  and  subsequent  spasmodic  contraction  give  rise  to  intense 
gastralgia  and  colic.  Quite  similarly,  it  is  commonly  noted  that  the 
passage  of  biliary  calculi  through  the  common  duct  or  of  renal  cal- 
culi through  the  ureters,  evokes  an  intense  pain  in  otherwise  practically 
insensitive  structures.  In  all  these  cases,  it  appears  that  the  adequate 
stimulus  is  distention,  pain  resulting  only  if  the  degree  of  the  distention 
exceeds  that  ordinarily  required  to  obtain  the  sensation  of  physiological 
fulness. 

As  far  as  the  cutaneous  sensation  of  pain  is  concerned,  it  may  be 
held  that  it  is  caused  either  by  an  overstimulation  of  the  receptors 
for  pressure  and  touch  or  by  the  excitation  of  specific  sense-organs  for 
pain.  The  second  view  is  more  commonly  accepted  to-day, ^  because 
the  sense  of  pain  possesses  a  punctiform  distribution  and  is  mediated 
by  end-organs  which  yield  solely  this  particular  sensation.  Thus, 
while  the  hyperexcitation  of  the  touch  points  may  give  rise  to  an 
unpleasant  sensation,  the  quality  of  the  latter  is  distinctly  different 
from  that  of  true  pain.^  In  addition,  it  might  be  mentioned  that  the 
tactile  and  temperature  senses  may  be  absent  in  certain  regions  of  the 
body,  but  not  the  pain  sense.  Thus,  while  the  stimulation  of  the 
cornea  readily  elicits  a  painful  sensation,  it  does  not  give  a  distinct 
sensation  of  touch.  Furthermore,  it  is  a  common  observation  that 
pathological  processes  may  give  rise  to  an  analgesia  or  loss  of  the  pain 
sense,  but  not  to  an  anesthesia  or  loss  of  the  sense  of  touch. 

Assuming,  therefore,  the  separate  existence  of  pain  points,  it  seems 
most  plausible  to  refer  this  sensation  to  the  free  endings  of  the  nerve 

1  Arbeiten  aus  dem  physiol.  Inst,  zu  Leipzig,  1896. 

2  Brown-Sequard,  Jour,  de  physiology,  vi,  1864,  and  Funcke,  Hermann's 
Handb.  der  Physiol.,  iii,  1883. 

3  Blix,  Zeitschr.  fur  Biol.,  xx  and  xxi,  1884-85. 


THE  SENSES  OF  PRESSURE  OR  TOUCH  741 

fibers.  1  These  sense-organs  possess  a  high  threshold  value,  i.e.,  they 
remain  insensitive  until  a  eertain  upper  limit  has  been  reached  when 
their  excitation  suddenly  evokes  pain.  It  is  also  evident  that  the  latent 
period  elapsing  between  their  stimulation  and  the  sensation,  is  unusually 
long;  moreover,  the  quality  of  this  sensation  may  be  materially  varied 
by  the  simultaneous  excitation  of  other  cutaneous  receptors.  For 
example,  a  burning  pain  results  whenever  the  nerve-endings  for  pain 
and  heat  are  activated  together  and  a  throbbing  pain,  whenever  the 
receptors  for  pain  and  touch  are  jointly  involved.  A  peculiar  alter- 
nating character  is  imparted  to  the  latter  sensation  by  the  systolic  dis- 
tention of  the  blood-vessels,  and  especially  if  it  meets  the  resistance  of 
hyperemic  and  infiltrated  tissues.  In  this  group  of  the  composite 
sensations  of  pain  also  belong  itching  and  tickling.  Alrutz,^  however, 
considers  these  impressions  as  being  evoked  by  special  nerve-endings, 
which  implies  that  they  represent  two  varieties  of  one  and  the  same 
modality    of    sensation. 

The  pain  sense  forms  an  important  protective  mechanism  of  the 
body,  because  it  acts  as  a  danger-signal,  by  means  of  which  abnormal 
processes  may  be  detected.  In  many  cases,  it  compels  rest  and  there- 
by favors  the  healing  of  a  diseased  part.  It  should  also  be  noted 
that  a  certain  tissue  may  become  painful  by  sympathy,  i.e.,  it  may 
develop  a  decided  tenderness  in  consequence  of  a  diseased  condition 
existing  elsewhere.  Diseases  of  the  heart  or  aorta  are  sometimes 
associated  with  pain  between  the  shoulders  or  with  pain  radiating  out- 
ward into  the  arms.  Referred  sensations  of  pain  are  also  experienced 
in  inflammatory  conditions  of  the  appendix,  gall-bladder  and  biliary 
ducts.  Head^  has  shown  that  the  innervation  of  certain  areas  of  the 
skin  is  intimately  related  to  that  of  certain  internal  organs,  because 
any  particular  segment  of  the  spinal  cord  sends  out  an  autonomic 
supply  of  nerve  fibers  as  well  as  one  to  the  corresponding  region  of  the 
integument.  In  certain  lesions  of  the  central  nervous  system,  the 
tactile  sensations  are  sometimes  wrongly  referred  to  regions  of  the 
body  which  are  actually  far  removed  from  those  in  which  they  have 
arisen.  ^lost  commonly,  however,  the  corresponding  area  on  the 
opposite  side  is  believed  to  be  the  seat  of  the  excitation.  This  faulty 
localization  is  designated  as  allochiria  and  constitutes  a  frequent 
tabetic  symptom. 

The  Temperature  Sense. — Contrary  to  the  view  that  the  sensa- 
tions of  heat  and  cold  arise  in  consequence  of  the  excitation  of  one  and 
the  same  end-organ,  it  is  now  commonly  beheved  that  they  represent 
two  distinct  modalities  which  are  mediated  by  separate  receptors. 
Thus,  if  a  pencil-like  probe  through  which  warm  water  is  made  to  cir- 
culate, is  slowly  drawn  across  the  surface  of  the  skin,  a  very  decided 
sensation  of  heat  is  generally  obtained  in  one  place  and  none  at  all 

1  Thunberg,  Xagel's  Handb.  der  Physiol.,  iii,  1905. 
-  Skand.  Archiv  fur  Physiol.,  xvii,  1905. 
3  Brain,  xvi,  1893. 


742  SPECIAL    SOMATIC    AND    VISCERAL   RECEPTORS 

in  the  area  immediately  adjoining.  Quite  similarlj-,  the  mapping  out 
of  the  surface  with  a  thermaesthesiometer  through  which  cool  water 
is  made  to  flow,  jdelds  sensations  of  cold  within  fields  of  no  thermal 
stimulation.  It  appears,  therefore,  that  the  integument  embraces 
a  series  of  warm  and  cold  points  which  when  properlj'  marked  in  dif- 
ferent colors,  will  be  seen  to  occupy  dissimilar  areas.  The  cold  spots 
are  more  numerous  than  the  warm  spots,  their  relationship  being  as 
13  :  1.5.  In  between  these  positive  fields  we  have  areas  which  do  not 
give  rise  to  a  distinct  temperature  sensation  and  are,  therefore,  called 
indifferent  fields.  But  these  temperature  points  are  not  confined  to  the 
skin  alone  but  are  also  disseminated  through  the  mucous  membranes 
of  the  mouth,  nose,  external  auditory  meatus,  and  anus.^ 


Cold  spots.  Heat  spots. 

Fig.  369. — Heat  axd  Cold  Spots  ox  P.ojt  of  Palm  of  Right  Haxb. 
The  sensitive  points  are  shaded,  the  black  being  more  sensitive  than  the  lined,  and 
these  more  sensitive  than  the  dotted  parts.     The  unshaded  areas  correspond  to  those 
areas  in  which  no  special  sensation  was  evoked.     (Goldscheider.) 

The  acuteness  of  the  temperature  sense  varies  in  different  regions 
of  the  body.  Thus,  it  has  been  observed  that  the  areas  situated  in 
the  midline  of  the  trunk,  are  less  sensitive  than  those  situated  more 
lateraUj^,  and  that  the  left  side,  in  general,  is  more  sensitive  than  the 
right.-  The  lateral  aspects  of  the  extremities  are  relativeh^  insensi- 
tive. The  same  holds  true  of  the  mucous  surfaces,  when  compared 
with  the  skin.  Inasmuch  as  the  latent  period  is  shortest  in  the  case 
of  the  cold  points,  the  stimulation  of  a  certaiu  area  of  the  integument 
most  generally  ehcits  the  sensation  of  cold  before  that  of  heat.  More- 
over, the  former  sensation  develops  more  rapidly  than  the  latter  and 
seems,  therefore,  to  be  the  more  intense.  Aluch  depends,  of  course, 
upon  the  size  of  the  area  stimulated.  Thus,  a  finger  immersed  in 
water  of  a  certain  temperature  always  gives  a  more  moderate  sensation 
than  the  entire  hand. 

Von  Frey  beheves  that  the  sensation  of  cold  is  mediated  by  the 
corpuscles  of  Krause.     The  activation  of  these  endings  may  also  be 

1  Zeitschr.  fur  Biol,  xx,  1884,  141 ;  also  Goldscheider,  ^ber  denSchmerz,  Berlin, 
1894,  and  Gesellsch.  Abhandlungen,  Leipzig,  1898. 

2  E.  H.  Weber,  Wagner's  Handworterbuch  der  Physiol.,  iii,  544. 


SENSES    OF   SMELL,    TASTE,    HUNGER   AND    THIRST  743 

effected  by  pressure  or  by  the  electrical  current,  a  fact  which  is  fre- 
quently cited  in  proof  of  the  law  of  the  specificity  of  nerve  energy. 
Under  ordinary  conditions,  these  receptors  are  expos(!d  to  a  constant 
temperature  by  reason  of  the  steady  stream  of  heat  which  escapes  from 
the  blood  and  permeates  the  tissues.  The  escape  of  this  heat  may  be 
retarded  by  warm  and  increased  by  cold  applications.  Consequently, 
these  thermal  stimulations  can  only  arise  if  the  heat  stagnation  or 
dissipation  surpasses  the  physiological  miniinum.  This  fact  explains 
the  sensation  of  cold,  experienced  whenever  the  circulation  of  a  part  is 
impeded  or  when  especially  good  conductors  of  heat  are  applied  to  the 
body-surface.  Since  a  more  rapid  fall  in  temperature  is  effected  by 
the  latter  procedure,  the  nerve-terminals  for  cold  are  more  vuickly 
reduced  below  the  point  of  minimal  thermal  stimulation.  In  other 
words,  the  chief  factor  in  the  production  of  the  sensations  of  heat  and 
cold  is  the  temperature  of  the  nerve-terminals  mediating  these  senses.^ 
Rather  difficult  to  explain  are  the  so-called  paradoxical  temperature 
reactions.  Menthol  applied  to  the  skin,  gives  rise  to  a  sensation  of 
cold,  while  carbon  dioxid  elicits  a  sensation  of  warmth.  A  sensation 
of  cold  may  also  be  evoked  by  stimulating  a  cold  spot  with  an  object 
possessing  a  temperature  of  45-50°  C.  Very  peculiar  sensations  of 
contrast  arise  in  consequence  of  the  adaptation  of  these  sense-organs 
to  certain  temperatures.  If  the  index  finger  of  one  hand  is  placed  in 
water  of  10°  C,  the  primary  sensation  of  cold  eventually  gives  way  to 
one  of  indifference.  If  this  finger  is  then  quickly  transferred  into 
water  of  11°  C,  a  distinct  sensation  of  warmth  will  be  obtained.  Quite 
similarly,  a  sensation  of  cold  may  be  evoked  by  transferring  the  finger 
from  water  of  39°  C.  into  water  of  38°  C.  Furthermore,  having  adapted 
the  fingers  of  one  hand  to  water  of  35°  C,  and  those  of  the  other  to  water 
of  25°  C,  their  simultaneous  transfer  into  water  of  30°  C.  produces  a 
sensation  of  cold  in  the  former  and  a  sensation  of  warmth  in  the  latter. 
If  a  warm  coin  is  applied  to  the  skin  for  some  time,  its  removal  gives 
rise  to  a  sensation  of  cold,  and  even  when  the  temperature  of  the  sur- 
rounding medium  is  only  very  slightly  below  that  of  the  skin. 


CHAPTER  LXI 

THE  SENSES  OF  SMELL,  TASTE,  HUNGER  AND  THIRST 

A.  SPECIAL  INTEROCEPTORS.     SMELL  AND  TASTE 

The  Structure  of  the  Olfactory  Organ. — The  mucous  membrane 
of  the  nose  consists  of  ciliated  reticular  cells  which  are  augmented,  in 
the  so-called  olfactory  area,  by  cells  possessing  all  the  characteristics  of 

^  Hering,  Sitzungsber.,  Akad.  zu  Wien,  Ixxv,  1877,  lOL 


744 


SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 


receiving  elements.  This  particular  area  occupies  the  nasal  septum 
and  adjoining  region  of  the  superior  turbinated  bone,  and  measures 
about  250  sq.  mm.  on  each  side.  It  is  sharply  differentiated  from  the 
general  lining  membrane  of  this  cavity  by  its  yellowish  brown  color. 
Each  nasal  cavity  may  be  divided  into  two  regions,  namely,  into 
the  so-called  regio  respiratoria  and  regio  olfactoria.  The  former  oc- 
cupies the  space  between  its  floor,  its  median  septum  and  the  inferior 
and  middle  turbinated  bones.  It  receives  its  sensory  nerve  supply 
chiefly  from  the  second  ramus  of  the  fifth  cranial  nerve  or  trigeminus, 
while  its  upper  part  is  innervated  bj^  the  first  branch  of  this  nerve. 

These  fibers  end  free  among  the 
lining  cells  and  mediate  general 
sensations,  namely,  those  of 
touch,  pain  and  temperature.  As 
such  they  may  also  be  stimulated 
by  irritating  emanations,  such  as 
are  derived  from  ammonia  and 
acetic  acid.  In  this  region  are 
also  found  numerous  mucous 
glands,  while  those  in  the  upper 
part  of  the  nose  are  tubular. 

The  olfacton'  regions  proper  con- 
sist of  non-ciliated  columnar  cells 
which  are  intermingled  with  a  large 
number  of  modified  epithelial  cells. '^ 
The  free  ends  of  these  slender  nerve  cells 
are  beset  with  six  to  eight  hair-like  pro- 
jections which  extend  through  the  limit- 
ing membrane  into  the  lumen  of  the 
nasal  cavity.  Their  basal  portions  are 
directly  continuous  with  the  fibers  of 
the  olfactory  nerve,  which  pass  through 

^       „„„      ^  _  the   pores  in  the  cribriform  plate  of  the 

Fig.  370. — Cells  of  the  Olfactory  .v-ju  j  j.iii         •     j. 

ry  ethmoid  bone  and  eventually  termmate 

,,,'.,,.,,,  in  the  olfactorv  bulb.     They  end  here  in 

a,   olfactory   cells;   o,  epithelial  cells;  n,        ,       ■      ,■         •     j.\        ^c     ^  i  ^■ 

^'  ,  •'         11  If     *         arborizations  m  the  olfactorv  glomeruli, 

central   process  prolonged   as   an   onactory    ^,     .     .       ,  ,         i  "  ^ 

nerve  fibril;  /,   nucleus;   c,   knob-like  clear    Their  further  course  has  been  mapped 
termination  of  peripheral  process;  A,  olfac-    out  in  one  of  the  precedmg  chapters, 
tory  hairs.     (After  v.  Brunn.)  In  the  lowest  vertebrates  the  olfac- 

tory organ  appears  in  the  form  of  a 
rounded  or  long  drawn  out  depression,  which  is  connected  with  the  olfactory  nerve. 
In  the  selachian,  these  grooves  are  connected  with  the  cavity  of  the  mouth  bj^  a 
gutter-like  prolongation.  In  the  frog,  this  connecting  passage  is  distinctly  tubular. 
The  cephalopods  are  in  possession  of  ciliated  olfactory  pockets  which  are  situated 
behind  the  eyes,  while  those  of  the  arthropods  are  located  upon  the  antennae. 

The  Specific  Action  of  the  Olfactory  Cells. — The  respiratory  currents 
of  air  traverse  chiefly  the  lowest  part  of  the  nasal  cavity,  while  the 
air  in  its  upper  region  remains  practically  stationary.     From  this  it 

1  Found  in  the  frog  by  Eckardt  in  1855,  and  in  mammals  by  Ecker  in  1856. 
M.  Schultze  gave  an  adequate  description  of  these  cells  in  1863. 


SENSES    OF    SMELL,    TASTE,    HUNGER    AND    THIRST  745 

may  he  inforrecl  that  the  odoriferous  particles  reach  the  olfactory  area 
by  diffusion.  Their  passage  upward,  however,  may  be  greatly  facili- 
tated by  the  act  of  snifRug  which  tends  to  displace  the  air  in  the  vicinity 
of  the  olfactory  cells  l)y  air  drawn  upward  through  the  fore  part  of 
this  cavity.  This  act  is,  of  course,  inspiratory  in  its  character,  but  it 
cannot  be  denied  that  the  aforesaid  cells  may  also  be  activated  by  the 
odoriferous  particles  derived  from  food  and  diverted  into  the  nasal 
cavity  by  the  expiratory  air.  The  senses  of  smell  and  taste  frequently 
act  together,  supi)lenienting  one  another.  In  fact,  it  frequently  hap- 
pens that  we  project  a  sensation  to  the  mouth  which  has  actually 
arisen  in  the  olfactory  cells.  The  preceding  data  also  serve  to  explain 
the  long  latent  period  usually  intei-vening  between  the  entrance  of  the 
odors  into  the  nostrils  and  the  sensation,  the  largest  part  of  this  period 
being  required  for  the  diffusion  of  the  particles  to  the  olfactory  area. 

Regarding  the  manner  in  which  the  olfactory  cells  are  stimulated, 
little  is  known.  It  is  evident,  however,  that  the  odorous  substances 
emit  particles  which  in  most  part  are  in  gaseous  form.  Having 
arrived  in  the  vicinity  of  the  olfactory  area,  they  enter  into  solution 
with  the  fluid  bathing  the  lining  membrane  and  eventually  with  the 
olfactory  cells  themselves.  But  only  those  bodies  are  capable  of  acting 
upon  these  cells  which  contain  a  chemical  binder,  the  so-called  odori- 
phore  group,  which  possesses  a  chemical  constitution,  enabling  it  to 
unite  with  the  substance  of  the  olfactory  epithelium.  "^  Hence,  smell  is 
essentially  a  chemical  process,  consisting  in  an  interaction  between  the 
activating  body  and  the  protoplasm  of  the  olfactory  cells.  •  It  is  diffi- 
cult to  show  this  fact,  because  it  is  practically  impossible  to  fill  our 
nasal  cavity  completely  with  a  fluid  which  is  non-irritating.  Aron- 
sohn,2  however,  claims  to  have  succeeded  in  evoking  sensations  of 
smell  by  means  of  isotonic  solutions  of  sodium  chlorid  to  which  odorif- 
erous substances  had  been  added.  In  support  of  this  chemical 
theory  it  might  be  mentioned  that  the  aquatic  animals  are  in  posses- 
sion of  a  projected  chemical  sense  of  smell  which,  in  the  nature  of 
things,  can  only  be  evoked  by  substances  held  in  solution. 

The  Power  of  Reaction  of  the  Olfactory  Cells — Olfactometry. — 
While  the  sensations  of  smell  may  also  be  evoked  by  stimulating  the 
olfactory  area  with  an  electrical  current,  the  adequate  stimulus  is, 
of  course,  the  odorous  molecule.  Zwaardemaker^  has  attempted  to 
determine  the  stimulating  quantity  of  different  odoriferous  substances 
by  means  of  an  instrument,  known  as  the  olfactometer.  It  consists 
as  a  rule  of  two  tubes  which  are  curved  at  their  ends  so  as  to  facihtate 
their  introduction  into  the  upper  part  of  the  nasal  passage.  The 
free  ends  of  these  tubes  are  surrounded  by  somewhat  larger  tubes 
(6  mm.  in  diameter)  which  are  imbibed  with  some  odorous  material. 
Naturally,  the  farther  the  outer  tubes  are  shoved  over  the  inner,  the 

iHaycraft,  Brain,  1888,  166;  also  Pussy,  Compt.  rendus,  1892. 

2  Archiv  fiir  Anat.  urid  Physiol.,  1886. 

'  Die  Physiologie  des  Geruchs,  Leipzig,  1895. 


746  SPECIAL    SOMATIC    AND    VISCERAL   RECEPTORS 

smaller  wiU  be  the  surface  capable  of  sending  odoriferous  particles 
into  the  air  inspired  through  this  tube.  This  method  enables  the 
experimentor  accurately  to  grade  the  stimulating  quantity. 

The  amount  of  substance  necessary  to  excite  the  olfactory  mechan- 
ism, is  extremely  small.  Thus,  0.01  mg.  of  mcrcaptan  may  be  per- 
ceived if  diffused  through  230  c.  cm.  of  air,  so  that  each  liter  of  the  latter 
contains  only  0,000,000,04  mg.  of  this  substance.  ^  The  threshold  value 
of  ether  and  oil  of  wintergreen  is  0.0005  mg.  per  liter  of  air.  Cam- 
phor stimulates  in  a  dilution  of  1  part  to  400,000,  musk  in  the  propor- 
tion of  1:8,000,000  and  vanilla  in  the  proportion  of  1:10,000,000. 
The  acuity  of  the  sense  of  smell  differs  in  different  persons,  and  is 
subject  to  various  exherent  factors.  It  is  said  that  women,  and  espe- 
ciallv  children,  are  more  sensitive  than  men;  moreover,  it  is  a  matter 


Fig.  371. — Single  Olfactometer.     {Zwaardemaker.) 

of  common  experience  that  this  sense  is  easily  fatigued,  but  if  fatigued 
so  as  to  be  no  longer  excited  by  one  kind  of  odorous  substance,  it 
is  still  in  a  condition  to  receive  other  modahties.  Quite  similarly, 
while  the  persons  seated  in  a  poorly  ventilated  room,  are  quite  unable 
to  perceive  the  foulness  of  the  air,  one  who  has  just  entered  immedi- 
ately notices  its  quahty.  Furthermore,  some  persons  are  absolutely 
insensitive  to  certain  odors;  at  least,  they  fail  completely  in  recognizing 
their  respective  qualities. 

In  this  connection,  attention  should  again  be  called  to  the  fact 
that  the  sense  of  smell  is  absent  in  some  animals  and  is  very  unequally 
developed  in  others.  For  this  reason,  the  osmatic  group  of  animals 
is  commonly  divided  into  a  microsmatic  and  macrosmatic,  the  latter 
class  including  such  animals  as  the  dog  and  rabbit.  Clearly,  the  ability 
of  the  dog  to  follow  the  trail  of  his  master  must  depend  upon  a  very 
acute  recognition  of  individual  odors,  the  stimulating  quantity  of 
1  Fischer  and  Penzoldt,  Liebig's  Annalen,  1887,  131. 


SENSES    OF    SMELL,    TASTE,    HUNGER    AND    THIRST  747 

which  must  be  infinitely  small.  In  animals  of  this  kind,  the  sense  of 
smell  must,  of  course,  become  prepotent  in  determining  their  behavior, 
both  volitioiially    and    r(>fle\ly. 

Qualitative  Differences  in  the  Olfactory  Sensations. — The  modali- 
ties of  smell  are  very  numerous  and  their  mimber  is  increased  still 
further  by  newly  acquired  sensations.  Thus,  a  chemist  is  generally 
trained  to  recognize  a  much  larger  number  of  substances  than  the 
layman,  but  even  that  person  whose  olfactory  impressions  have  been 
most  minutely  associated,  is  quite  unable  to  classify  them  in  accordance 
with  their  qualities.  In  most  cases,  one  must  be  content  with  charac- 
terizing them  as  agreeable  or  disagreeable.  A.  von  Haller,  however, 
has  (livid(Hl  them  into  odores  suaveolentes,  odorcs  intermedise  and 
odores  factores.  In  this  regard  the  sense  of  smell  differs  very  greatly 
from  the  othei's,  because  it  does  not  permit  of  at  least  a  general  arrange- 
ment of  these  sensations  into  a  fundamental  and  a  complex  group. 
The  following  classification  of  Zwaardemaker  which  is  based  upon  the 
observations  of  Linne,  tends  to  overcome  this  defect  in  a  slight  degree 
by  recognizing  at  least  certain  vague  similarities  between  them: 

L  Ethereal  odors,  depend  upon  the  presence  of  such  substances  as  the  esters. 
They    are    emitted    by   different    fruits. 

2.  Aromatic  odors  are  given  off  by  such  substances  as  camphor,  resinous  oils 
and  citron. 

3.  Fragrant  odors,  comprise  the  various  odors  of  flowers  and  perfumes. 

4.  Ambrosial  odors,  are  typified  by  amber  and  musk. 

5.  Garlic  odors,  are  emitted  by  the  onion,  garlic,  sulphur,  and  the  compounds 
of  selenium  and  tellurium. 

6.  Burning  odors,  are  given  off  by  benzol,  phenol,  tobacco  smoke  and  similar 
substances. 

7.  Caproic  odors,  find  their  origin  in  the  caproic  and  caprillic  acids  of  sweat, 
cheese,  and  the  spermatic  and  vaginal  secretions. 

8.  Repulsive  odors,  are  yielded  by  many  plants,  such  as  acanthus. 

9.  Nauseating  or  fetid  odors,  are  given  off  by  putrefying  substances  of  animal 
origin. 

A  conflict  between  these  sensations  arises  whenever  two  odors 
are  permitted  to  act  at  the  same  time.  While  the  result  then  ob- 
tained, is  largely  dependent  upon  the  odors  selected,  the  strongest 
most  generally  predominates  in  consciousness.  At  other  times,  they 
may  alternate  with  one  another  without,  however,  being  fused  into  an 
intermediate  compound  sensation.  An  actual  fusion  does  not  result, 
as  a  rule,  unless  they  belong  to  one  and  the  same  group  of  odors, 
A  mixture  of  two  or  more  odors  which  presents  a  modality  quite 
different  from  those  of  the  fundamental  odors,  may  be  effected  by 
such  substances  as  vanilhn  and  bromin,  turpentine  and  xylol,  and 
others.  1  Certain  odoriferous  substances  may  also  be  mixed  in  certain 
proportions  to  annul  their  individual  effects.  A  neutrahzation  of 
this  kind  is  obtained  by  mixing  4  grains  of  iodoform  with  200  grains 
of  balsam  Peru. 

^  Nagel,  Zeitschr.  fur  Psych,  und  Physiol,  der  Sinnesorgane,  xv. 


748 


SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 


The  Structure  of  the  Taste  Buds. — These  peculiar  bodies  are 
widely  distributed  through  the  mucous  membrane  lining  the  mouth 
and  pharynx.  "^  They  are  found  upon  the  tip,  margins  and  posterior 
region  of  the  dorsal  aspect  of  the  tongue,  but  not  upon  its  lower  sur- 
face. Limited  numbers  of  them  may  also  be  detected  in  the  mucosa 
of  the  fauces  and  adjoining  regions  of  the  pharynx  and  epiglottis. 
In  children  they  are  more  numerous  than  in  adults,  invading  even  the 
adjoining  regions  of  the  cheeks  and  posterior  fauces.  These  outlying 
taste  buds  atrophy  in  later  years.  This  retrogression  also  involves 
those  occupying  the  median  area  of  the  tongue. 

The  taste  buds  appear  as  oval  bodies,  measuring  SOjj.  in  length 
and  40)U  in  width.  Externally  they  are  enveloped  by  the  cortical 
reticular  cells,  while  their  central  portion  is  occupied  by  a  number  of 


^*^   ^(% 


Fig.  372.  Fig.  373. 

Fig.  372. — Diagrammatic  Representation  of  Circumvallate  Papilla  Showing  the 
Position  of  the  Taste-buds. 

Fig.  373. — Transverse  Section  Through  a  Taste-bud. 

A,  taste  pore;  B,  spindle-shaped  cells  of  the  taste-bud;  C,  reticular  cells;  D,  nerve 
fibers  terminating  among  its  cells. 

closely  packed,  elongated  cells  which  send  their  hair-like  projections 
into  the  depression  overlying  them.  This  depression,  which  is  known 
as  the  taste-pore,  is  the  seat  of  the  stimulation  leading  to  taste  sensa- 
tions. The  nerve  fiber  enters  through  the  basal  pole  of  the  taste-bud 
and  terminates  in  arborizations  among  the  different  gustatory  cells. 
These  fibers  lose  their  medullary  sheath  directly  before  entering. 

It  has  just  been  stated  that  these  end-organs  communicate  with 
the  general  cavity  of  the  mouth  through  the  taste-pore.  Many  of 
them,  however,  do  not  lie  directly  upon  the  surface,  but  occupy  a  posi- 
tion in  the  depressions  between  the  different  elevations  of  the  mucosa. 
The  tongue,  for  example,  exhibits  three  types  of  elevations  which,  in 
accordance  with  their  shape,  are  known  as  filiform,  fungiform  and 
circumvallate  papillae.  Those  mentioned  last  are  found  chiefly  upon  the 
posterior  aspect  of  this  organ  and  are  beset  with  an  especially  large 

1  First  described  by  Loven  and  Schwalbe  in  1867. 


SENSES    OF    SMELL,    TASTE,    HUNGER    AND    THIRST 


749 


number  of  taste  buds.  Sometimes  as  many  as  one  hundred  of  these 
may  be  congregatetl  in  the  depression  encirchng  a  single  papilla.  It 
is  to  be  noted  especially  that  they  are  well  protected  against  the  ordi- 
nary mechanical  stimuli  which  arise  in  consequence  of  the  movements 
of  the  tongue 

The  Innervation  of  the  Taste  Buds. — In  accordance  with  their  wide 
distribution,  it  cannot  surprise  us  to  find  that  their  innervation  can 
only  be  accomplished  with  the  help  of  several  nerves.  Those  directly 
involved  are  the  lingual  nerve,  a  branch  of  the  inferior  maxillary 
division  of  the  trigeminus,  and  the  glossopharyngeal  and  vagus  nerves. 
The  first  innervates  the  anterior  region  of  the  tongue,  or  about  two- 
thirds  of  the  entire  organ;  the  second  the  posterior  part  and  root  of 
the  tongue  as  well  as  the  adjoining  soft  parts,  and  the  third  the  epi- 


C&sseri&n  G&n^lion 


Fig.  374. — Diagram  Showing  Origin  and  Course  of  the  Nerve  Fibers  of  Taste. 


glottis  and  mucosa  of  the  larynx  proper.  It  is  to  be  noted,  however, 
that  the  fibers  allotted  to  the  lingual  nerve,  pursue  a  double  course,  i.e., 
while  some  of  them  remain  within  the  system  of  the  trigeminus,  others 
leave  it  to  enter  that  of  the  chorda  tympani.  The  latter,  in  turn, 
either  continue  in  this  system  of  the  seventh  cranial  nerve  (portio 
intermedia  Wrisbergii)  or  pass  over  to  the  glossopharyngeal  nerve. 
It  seems  certain,  however,  that  the  fibers  originally  allotted  to  the 
glossopharyngeus  and  vagus  nerves,  pursue  a  straight  course  to  their 
respective  nuclei  in  the  medulla. 

The  function  of  the  glossopharyngeus  is,  of  course,  quite  evident, 
because  cutting  this  nerve  leads  to  a  loss  of  the  sensations  of  taste 
in  the  region  innervated  by  it  and  eventually  to  a  complete  atrophy  of 
the  corresponding  taste  buds.  The  fact  that  the  chorda  tympani 
takes  part  in  the  conduction  of  taste-impulses,  may  be  evinced  at  any 
time  by  stimulating  this  nerve  as  it  traverses  the  tympanic  cavity. 
The  usual  effect  of  this  procedure  is  a  metallic  or  sour  taste,  but  some 


750  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

investigators  also  claim  to  have  produced  sweet  and  bitter  sensations.^ 
Much  diversity  of  opinion,  however,  prevails  regarding  the  central 
distribution  of  these  fibers.  Thus,  Krause^  states  that  the  total 
extirpation  of  the  Gasserian  ganglion  is  followed  by  a  loss  of  taste  in 
the  corresponding  anterior  region  of  the  tongue.  Gushing,^  moreover, 
has  found  that  this  operation  never  impairs  the  taste  sensations  from 
the  posterior  part  of  the  tongue.  It  may  be  concluded,  therefore, 
that  the  fibers  from  this  region  traverse  the  petrosal  ganglion  and  enter 
the  sensory  nucleus  of  the  glossopharyngeus  in  the  medulla.  The 
fibers  from  the  taste  buds  of  the  larynx  must  necessarily  follow  the  high- 
way of  the  vagus,  while  those  from  the  anterior  two-thirds  of  the  tongue 
must  for  the  present  be  assumed  to  enter  by  way  of  the  trigeminus 
and  facial  nuclei. 

The  Activation  of  the  Taste  Buds. — When  food  is  taken  into  the 
mouth,  it  is  subjected  to  a  mechanical  as  well  as  chemical  reduction, 
with  the  result  that  it  is  brought  into  intimate  relation  with  the  largest 
possible  number  of  taste  buds.  Substances  to  be  tasted  must,  of  course, 
be  in  a  fluid  state.  This  end  is  generally  attained  with  the  aid  of  the 
saliva  which  not  only  acts  as  a  solvent,  but  also  tends  to  carry  the  par- 
ticles into  the  crevices  between  the  base  of  the  tongue  and  the  fauces, 
and  facilitates  their  entrance  into  the  furrows  around  the  papillae 
in  which  the  taste  buds  are  situated.  Glearly,  the  movements  of  the 
tongue  are  not  essential  to  taste,  but  materially  facilitate  the  reduction 
and  distribution  of  the  food.  It  may  be  concluded,  therefore,  that 
the  sensation  of  taste  arises  in  consequence  of  a  reaction  between  the 
sapid  substance  and  the  protoplasm  of  the  gustatory  cells,  through  the 
intervention  of  their  hair  processes.^  It  must  also  be  evident  that 
this  reaction  can  only  take  place  if  the  sapid  agent  possesses  definite 
chemical  properties.  It  is  true,  however,  that  chemically  allied  bodies 
need  not  exhibit  identical  characteristics  in  this  regard.  Thus, 
sugar,  saccharin  and  lead  acetate  all  give  rise  to  a  sweet  taste,  while  the 
starches  do  not.  In  addition,  it  should  also  be  remembered  that  sensa- 
tions of  taste  may  be  evoked  by  substances  contained  in  the  blood. 
Thus,  the  j  aundiced  person  frequently  experiences  a  bitter  taste,  while  the 
diabel ic  pei  ceives  sweet.  It  has  also  been  claimed  that  sensations  of  taste 
may  be  evoked  by  electrical  means,  but  not  by  mechanical  or  thermal 
stimuli.  Thus,  it  is  usually  stated  that  the  anode  gives  rise  to  a  sour 
and  the  cathode  to  a  bitter  sensation.  This  phenomenon  has  been 
referred  by  some  experimenters  to  a  direct  excitation  of  the  taste  buds,^ 
while  others  contend  that  it  arises  only  in  consequence  of  electrolytic 
dissociations  at  the  seat  of  the  electrodes.^     At  the  present  time  no 

^  Blau,  Berliner  klin.  Wochenschr.,  xlv,  1879. 
2  Miinchener  med.  Wochenschr.,  xlii,  1895. 

^  Bull,  of  the  Johns  Hopkins  Hospital,  Baltimore,  xiv,  1903,  77. 
*  Zwaardemaker,  Ergebn.  der  Physiol.,  Wiesbaden,  1903. 

«  Ohrwall,  Skand.  Archiv  fur  Physiol.,  ii,  1891,  and  Zeynek,  Zentralbl.  fiir 
Physiol.,  xiii,  1898. 

'Hermann,  Grundrisse  der  Physiol.,  1872,  337. 


SENSES    OF    SMELL,    TASTE,    HUNGER    AND    THIRST  751 

facts  are  at  our  disposal  which  could  ho  used  to  exclude  the  second 
view,  and  hence,  we  must  regard  tlu;  excitation  of  the  taste  buds  V>y 
inadeciuatc  stimuli  as  not  proven, 

The  Power  of  Reaction  of  the  Taste  Buds.  Gustometry. — The 
acuity  of  tiie  sense  of  taste  may  be  tested  by  bringing  solutions  of 
different  concentration  in  relation  with  different  points  of  the  tongue 
and  ascertaining  the  dilution  which  barely  suffices  to  incite  a  sensation. 
These  fluids  may  be  applied  either  with  a  camel's  hair  brush  or  a  drop- 
per, but  inasmuch  as  the  tongue  is  also  equipped  with  tactile,  temper- 
ature and  pain  receptors,  they  must  be  non-irritating  and  should  be 
heated  to  a  few  degrees  below  the  temperature  of  the  body.  Very 
cold  and  very  warm  solutions  diminish  the  sensitiveness  of  these  end- 
organs.  Care  must  also  be  taken  that  the  substances  selected  for 
these  tests,  do  not  activate  the  olfactory  cells,  and  that  they  are  not 
spread  to  other  regions  of  the  oral  cavity  by  movements  of  the  tongue. 

All  sensations  of  taste  are  preceded  by  a  definite  latent  period, 
which  is  caused  in  part  by  the  delayed  action  of  the  sense-organs 
themselves,  and  in  part  by  the  fact  that  the  substances  must  first  be 
dissolved.  Oth*r  factors  to  be  controlled  are  the  size  of  the  field 
stimulated,  the  length  of  the  period  during  which  the  stimulus  is  allowed 
to  act  and  the  general  sensitiveness  of  the  mucous  membrane.  It  is 
a  matter  of  common  experience  that  the  receptive  power  of  the  latter 
is  materially  altered  by  habits,  such  as  the  use  of  alcohol  and  tobacco. 
The  values  of  the  latent  period  for  the  tip  of  the  tongue  are  as  follows:^ 

Sodium  chlorid 0 .  308  sec. 

Sugar • 0.446  sec. 

Sulphuric  acid 0 .  536  sec. 

Quinine 1 .  082  sec. 

The  Topography  of  the  Sense  of  Taste. — While  the  sensations  of 
taste  are  very  numerous,  it  is  possible  to  arrange  them  in  four  funda- 
mental groups,  namely,  as  sweet,  bitter,  acid  and  salty.  Such  modali- 
ties as  burning,  astringent,  aromatic  and  oily  are  composite  in  their 
nature  and  require  the  simultaneous  activation  of  the  olfactory  cells 
as  well  as  of  the  sense-organs  for  touch  and  temperature.  Thus, 
weak  acids  give  an  astringent  sensation  in  addition  to  a  distinct  taste 
of  sour,  while  strong  acids  ampUfy  the  primary  impression  by  a 
burning  sensation.  A  similar  amplification  of  common  sensibility  is 
effected  by  alum  and  pepper. 

Even  the  fundamental  taste  sensations  may  be  combined  to  give 
a  fused  or  compound  effect.  Thus,  weak  solutions  of  sweet  and  salty 
substances  may  yield  a  sensation  of  flatness  or  alkalinity,  and  a  weak 
sensation  of  sweet  may  be  completely  neutrahzed  by  the  addition  of 
a  few  grains  of  sodium  chlorid.  Quite  similarly,  the  addition  of 
sugar  to  lemon  juice  diminishes  the  acidity  of  the  latter  and  gives  rise 
to  a  mixed  sensation  in  which  the  components  may  be  clearly  recognized. 

iKiesow,  Wundt's  philos.  Studien,  ix,  x  and  xii,  1894-96;  also  Zeitschr.  fiir 
Psych,  and  Physiol,  der  Sinnesorgane,  xxvii,  1901. 


752  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

It  is  also  to  be  noted  that  the  tongue  is  not  equally  sensitive  to  all 
four  primary  tastes.  By  far  the  greatest  acuity  for  sweet  prevails 
upon  the  tip  of  tongue,  while  bitter  is  most  clearly  perceived  upon  its 
posterior  aspect  in  the  vicinity  of  the  circumvallate  papillae.  The 
acuity  for  sweet  decreases  gradually  from  before  backward  and  that 
for  bitter  in  the  opposite  direction.  The  sour  taste  is  most  highly 
developed  in  the  central  fields  of  the  marginal  regions  of  the  tongue, 
and  the  salty  taste  in  its  antero-lateral  regions.  Pecuharly  enough, 
these  different  sensibilities  may  be  varied  by  means  of  certain  drugs. 
Thus,  we  find  that  the  application  of  a  solution  of  cocain  to  the  sur- 
face of  the  tongue  first  of  all  diminishes  our  acuity  for  the  compound 
impressions,  so  that  acids  produce  merely  a  sour  taste  without  any 
astringent  or  burning  admixture.^  Next  in  order  follow  the  fundamen- 
tal sensations,  namely,  bitter,  sweet,  sour  and  salty.  A  very  similar 
effect  may  be  produced  by  chewing  the  leaves  of  gymnemna  sylvestre. 
In  this  case,  the  sensations  of  sweet  and  bitter  are  destroyed,  while  the 
acid  and  salty  tastes,  as  wellas  the  general  sensibility,  are  not  impaired.^ 

These  facts  recall  to  our  minds  the  interesting  question  regarding 
the  specificity  of  the  taste  buds,  it  being  entirely  probable  that  the 
four  fundamental  qualities  of  taste  are  mediated  by  four  different 
types  of  end-organs.  Thus,  Ohrwall  has  shown  that  certain  papillae 
react  only  to  particular  kinds  of  sapid  substances.  Of  the  total  num- 
ber of  125  examined,  98  could  be  activated  by  different  substances. 
Of  this  number,  60  yielded  three  modahties  of  taste  sensations,  while 
12  gave  sweet  and  acid,  12  only  acid,  7  bitter  and  acid,  4  sweet  and 
bitter,  and  3  only  sweet.  In  addition,  it  has  been  pointed  out  that 
parabrombenzoic  sulphinid  gives  rise  to  a  sensation  of  sweet  when 
placed  upon  the  tip  of  the  tongue,  and  to  a  sensation  of  bitter  when 
applied  to  its  posterior  surface.  Quite  similarly,  sodium  sulphate 
tastes  salty  upon  the  tip  of  the  tongue  and  bitter  upon  its  posterior 
region. 

B.  GENERAL  INTEROCEPTORS,  APPETITE,  HUNGER  AND  THIRST 

Appetite. — It  has  been  mentioned  above  that  in  the  lower  forms 
the  sensations  of  smell  and  taste  occupy  the  position  of  exteroceptors, 
while  in  the  higher  animals,  they  assume  more  especially  the  function 
of  interoceptors.  In  addition,  the  latter  group  also  embraces  a  large 
number  of  peculiar  internal  sensations,  chief  among  which  are  the 
sensations  of  appetite,  hunger  and  thirst.  Regarding  the  first,  it 
has  commonly  been  held  that  it  is  merely  a  mild  form  of  hunger  and  is 
not  mediated  by  separate  receptors.  Cannon  and  Washburn,^ 
on  the  other  hand,  seem  to  differentiate  sharply  between  these  sensa- 

^  V.  Amrep,  Pfltiger's  Archiv,  xxi,  1880,  and  Knapp,  Archiv  fiir  Augenheilk., 
1885. 

^  Edgeworth  and  Hooper,  Nature,  xxxv,  1887,  565. 
^  Amer.  Jour,  of  Physiol.,  xxix,  1912,  441. 


SENSES    OF   SMELL,    TASTE,    HUNGER    AND    THIRST  753 

tions  and  characterize  appetite  as  a  pleasurable  mental  state,  which  has 
its  origin  in  an  excitation  of  the  mechanisms  for  taste  and  smell,  while 
hunger  constitutes  a  more  disagreeal)le  and  stronger  sensation  which 
arises  in  certain  receptors  in  the  walls  of  the  stomach,  Carlson^  who 
has  studied  this  sul)ject  more  recently,  adheres  to  this  classification. 

These  general  contentions,  however,  do  not  aid  us  very  materially 
in  establishing  a  physiological  basis  for  these  sensations;  in  fact,  it 
must  be  admitted  that  we  know  practically  nothing  regarding  them. 
Besides  the  sensory  element  imparted  to  them  by  the  senses  of  smell 
and  taste,  they  also  possess  a  gastric  component  introduced  by  the 
simultaneous  excitation  of  some  sensory  unit  of  the  gastric  mucosa. 
Thus,  it  is  a  matter  of  common  experience  that  the  ingestion  of  food 
blunts  the  appetite  as  well  as  the  hunger,  while  both  are  evoked  by 
total  abstinence.  Still,  certain  conditions  may  be  introduced  which 
lead  to  a  dissociation  of  these  sensations.  For  example,  while  a  pro- 
longed fast  very  frequently  diminishes  and  destroys  all  the  pleasurable 
sensations  connected  with  the  thought  of  food,  the  sensation  of  hunger 
may  persist  for  some  time  thereafter.  Again,  the  mere  passage  of  the 
food  through  the  esophagus  may  satisfy  the  appetite,  in  spite  of  the 
fact  that  the  hunger  contractions  of  the  stomach  continue.  Quite  simi- 
larly, the  gradual  emptying  of  the  stomach  after  a  meal  usually  restores 
the  appetite  at  a  time  when  actual  hunger  is  not  experienced  as  yet. 

The  contrary  sensation  of  appetite  is  an  aversion  to  food,  which 
arises  whenever  the  gastric  reservoir  is  well  filled  or  when  the  body  as 
a  whole  is  unable  to  assimilate  a  particular  kind  of  food.  Thus,  it 
frequently  happens  that  we  acquire  an  aversion  to  fat  or  gelatin  in 
spite  of  the  fact  that  these  substances  possess  a  distinct  nutritive  value. 
As  in  the  case  of  appetite,  this  sensation  arises  in  special  interoceptors, 
but  also  embraces  a  gastric  element. 

Hunger. — The  sensation  of  hunger  is  primarily  projected  to  the 
region  of  the  stomach,  but  may  also  make  itself  felt  by  the  more 
general  sensations  of  mental  and  bodily  fatigue  and  functional  de- 
pression. To  begin  with,  there  is  a  local  feeling  of  emptiness  in  the 
stomach  which  is  intensified  in  the  course  of  time  into  a  painful  sensa- 
tion. Furthermore,  this  sensation  shows  a  definite  intermittency  and 
may  be  temporarily  abolished  by  the  ingestion  of  even  indigestible 
material.  These  three  facts  seem  sufficient  to  disprove  one  of  the  hy- 
pothesis which  holds  that  hunger  is  a  general  sensation  and  is  caused  by 
certain  changes  in  the  metabolism  of  the  tissues,  particularly  in  that  of 
the  nervous  tissues.  ^  Another  view  is  that  hunger  is  caused  by  the 
stimulation  of  certain  afferent  nerves  in  the  gastric  mucosa  in  conse- 
quence of  the  distention  of  the  glands  by  accumulated  secretion  (Beau- 
mont). No  facts  can  be  mentioned  in  support  of  this  hypothesis  other 
than  that  sensations  of  hunger  are  generally  followed  by  a  sudden  out- 

^  Carlson  and  Braafladt,  Am.  Jour,  of  Physiol.,  xxxvi,  1914,  153. 

2  Turro,  Zeitschr.  fiir.  Psych,  und  Physiol,  der  Sinnesorgane,  xlv,  1911. 


754  SPECIAL    SOMATIC    AND    VISCERAL    RECEPTORS 

pouring  of  gastric  juice.  A  third  hypothesis  is  that  hunger  is  due 
to  the  stimulation  of  certain  afferent  nerves  in  the  stomach  by  the 
contraction  of  its  musculature.  In  support  of  this  view  might  be  men- 
tioned the  contracted  state  of  the  empty  stomach,  the  periodic  peri- 
staltic waves  passing  over  it,  the  abolition  of  this  sensation  after  the 
introduction  of  indigestible  substances,  and  the  rumbling  gastric  noise 
produced  when  this  sensation  is  experienced.  Cannon  and  Washburn 
have  proved  that  the  sensation  of  hunger  occurs  simultaneously  with 
increases  in  intragastric  pressure.  In  nervous  persons,  however,  and 
especially  in  women,  loud  rumbling  noises  are  frequently  heard 
without  being  associated  with  this  sensation. 

Carlson^  has  repeated  these  observations  upon  a  man  with  a 
gastric  fistula  established  after  the  occlusion  of  the  esophagus  by  a 
cicatrix.  It  is  stated  that  there  is  a  fairly  close  correspondence  be- 
tween the  duration  of  the  contractions  and  the  duration  of  the  sub- 
jective sensation  of  hunger.  A  similar  relationship  was  noted  between 
the  intensity  of  this  sensation  and  the  strength  and  rapidity  of  develop- 
ment of  the  contractions.  Moreover,  while  a  distinct  sensation  of 
hunger  could  be  produced  by  suddenly  inflating  a  balloon  placed  in 
the  stomach,  it  could  not  be  evoked  by  tactile  stimulation  of  the  gas- 
tric mucosa.  The  peripheral  genesis  of  this  sensation,  therefore, 
seems  established,  although  no  definite  data  have  been  obtained  regard- 
ing the  nervous  mechanism  involved  in  it. 

Attention  should  also  be  called  at  this  time  to  the  continued  sensa- 
tion of  hunger  experienced  by  the  diabetic  patient  which  prompts  him 
to  eat  superfluous  amounts  of  food.  A  similar  condition  frequently 
results  in  persons  whose  lower  intestine  has  been  made  to  open  through 
the  abdominal  wall  in  order  to  reheve  an  obstruction  in  the  rectum  or 
neighboring  parts  (Carcinoma).  Under  this  condition  the  pangs  of 
hunger  are  experienced  even  when  the  stomach  is  comfortably  filled 
with  food.  In  view  of  these  facts,  it  might  be  well  to  recognize  two 
types  of  hunger,  namely,  gastric  hunger  which  is  present  normally,  and 
general  or  somatic  hunger  which  is  brought  into  play  under  unusual 
conditions. 

Thirst. — The  sensation  of  thirst  is  specifically  referred  to  the 
pharynx,  unless  there  is  a  general  scarcity  of  water,  in  which  case  this 
local  sensation  is  augmented  by  fatigue,  anguish,  pain  and  suffering. 
In  the  first  instance,  the  sensation  is  evoked  in  a  circumscribed  region 
of  the  pharynx  situated  directly  in  the  path  of  the  currents  of  air  ebb- 
ing back  and  forth  between  the  outside^'and  the  lungs.  It  is  conceiva- 
ble that  the  terminals  of  the  glossopharyngeus  nerve  are  specifically 
adapted  to  perceive  variations  in  the  water  content  of  the  cells  lining 
this  area,  because  thirst  is  experienced  as  soon  as  the  latter  becomes  dry 
and  even  at  a  time  when  the  body  as  a  whole  is  abundantly  supphed 
with  water.  A  local  moistening  then  suffices  to  give  relief  without  that 
water  is  actually  taken  into  the  stomach.  But,  these  lining  cells  may 
1  Am.  Jour,  of  Physiol.,  xxxi,  1912,  175. 


SENSES    OF   SMELL,    TASTE,    HUNGER    AND    THIRST  755 

also  become  dry  when  the  general  water  content  of  tlie  body  is  depreci- 
ated, because  water  is  constantly  transferred  by  them  to  the  respira- 
tory air.  While  a  local  moistening  also  gives  relief  in  this  case,  it  is 
not  lasting  and  can  only  l)e  made  so  by  taking  water  into  the  stomach. 
When  water  is  long  withheld,  all  the  tissues  become  water-starved  so 
that  the  simple  sensation  of  phanjngeal  thirst  becomes  augmented  by 
more  distressing  symptoms,  such  as  pain  and  a  bodily  and  mental  an- 
guish and  discomfort.  It  is  conceivable  that  these  sensations  arise  in 
the  receptors  allotted  to  the  different  tissues.  If  this  assumption  is 
correct,  a  second  variety  of  thirst  must  be  recognized  which  may  be 
designated  as  general  or  tissue  thirst.  The  testimony  of  those  persons, 
however,  who  have  been  without  food  and  water  for  long  periods  of 
time,  tends  to  show  that  these  symptoms  of  extreme  discomfort  and 
pain  disappear  in  the  course  of  time,  so  that  death  by  starvation  need 
not  necessarily  be  accompanied  by  extreme  suffering.^ 

^  Hertz,  The  Sensibility  of  the  AUmentary  Canal,  London,  1911;  Sven  Hedin, 
in  his  travels  through  Thibet,  alludes  to  many  cases  of  self-imposed  abstinence  by 
the  Holy  Men  of  Brahma. 


SECTION  XXI 
THE  SENSE  OF  HEARING 


CHAPTER  LXII 
THE  CAUSE  AND  CHARACTER  OF  THE  SOUND  WAVES 

The  Cause  of  Sound  Waves. — Sound  waves  arise  in  consequence 
of  the  vibration  of  elastic  bodies.  If  a  metal  plate  is  suspended  in 
space  and  its  central  area  is  struck  with  the  end  of  a  rod,  it  suffers  a 
displacement  of  its  constituents  which  permit  it  to  deviate  in  the 
direction  of  the  stroke.  Having  attained  its  extreme  position  in  this 
direction,  it  immediately  swings  back  toward  the  opposite  side,  and 
so  on  until  it  has  again  attained  its  equilibrium.  These  deviations 
of  the  plate  in  turn  give  rise  to  a  vibration  of  the  air  surrounding  it, 
because  those  molecules  which  lie  directly  ia  its  path  will  be  alternately 
condensed  and  rarefied.  In  this  way,  the  vibrations  of  the  sonorous 
body  are  transferred  into  undulations  of  an  elastic  medium,  formed 
by  the  air.  The  first  are  stationary  and  the  second  progressive  in 
their  nature. 

Vibrations  of  a  sonorous  bodj^  may  be  either  transverse,  as  in  a 
string,  or  longitudinal,  as  in  a  rod.  The  undulations  in  a  medium, 
however,  must  of  necessity  be  longitudinal,  because  only  forward  im- 
pulses or  pushes  can  be  communicated  from  one  molecule  to  another. 
Thus,  sound  is  conveyed  onward  by  an  undulatory  or  wave-like 
motion  in  air,  similar  to  that  exhibited  by  particles  of  water  during 
the  translation  of  a  wave.  In  water,  however,  the  different  particles 
move  in  a  circle,  while  in  air  they  move  in  a  straight  line,  backward 
and  forward,  in  the  direction  in  which  the  sound  is  projected. 

The  initial  energy  of  the  undulations  in  air  is  gradually  reduced  as 
they  pass  away  from  the  sonorous  body,  so  that  the  sound  diminishes 
constantly  until  it  becomes  completely  neutralized.  This  reduction, 
however,  takes  place  at  a  more  rapid  rate  than  is  theoretically  sug- 
gested by  the  law  of  inverse  squares.  The  reason  for  this  discrepancy 
is  that  vibration  leads  to  friction  and  friction  to  heat,  generated,  of 
course,  at  the  expense  of  the  initial  energj\ 

Sound  waves  may  also  be  propagated  by  media  other  than  air,  in 
fact,  in  many  instances  with  much  better  results.  Thus,  they  pass 
along  rods  of  wood  with  the  greatest  ease,  and  also  along  cords  and 
wires.     Practical  use  has  been  made  of  this  fact  in  the  construction 

756 


THE   CAUSE   AND   CHARACTER   OF  THE   SOUND   WAVES        757 

of  the  earlier  forms  of  stethoscopes  (Laennec)  which  usually  consisted 
of  a  wooden  cylinder  perforated  through  its  axis  and  enlarged  at  its 
ends.  Furthermore,  their  initial  energy  may  be  protected  against  loss 
by  sending  them  through  narrow  tubes,  because  they  are  then  no  longer 
propagated  as  concentric  spheres,  but  are  reflected  from  the  walls  of 
the  tube.  We  shall  see  later  on  that  this  is  true  of  the  sound  waves 
traversing  the  external  auditory  meatus. 

Any  sound  produced  near  at  hand,  seems  to  reach  our  ears  instan- 
taneously. In  reahty,  however,  there  is  a  distinct  interval  between 
the  moment  of  its  production  and  the  moment  when  it  produces  its 
stimulation  in  the  internal  ear.  This  latency  is  caused  in  part  by  a 
certain  sluggishness  of  the  receptor,  and  in  part  by  the  fact  that  sound 
waves  require  time  for  their  propagation  through  the  medium.  A 
distant  locomotive  or  steam  boat  is  seen  to  discharge  a  certain  volume 
of  steam  through  its  vibrator  long  before  the  sound  produced  thereby 
actually  reaches  our  ears,  and  the  flash  of  lightning  is  seen  long  before 


4 


Fig.  375. — Laexnec  Stethoscope. 

the  thunder  is  heard.  While  altitude,  temperature  and  the  general 
character  of  the  medium  have  much  to  do  with  the  propagation  of  the 
vibrations  from  molecule  to  molecule,  it  may  be  said  that  the  velocity 
of  sound  is  340  m.  in  a  second.  Its  speed,  however,  is  proportional  to 
its  intensitj^,  i.e.,  loud  sounds  travel  more  rapidly  than  those  possessing 
a  low  quality.  Through  water  sound  is  propagated  at  the  rate  of 
about  1450  m.  in  a  second,  and  through  wood  at  the  rate  of  about 
13,000  m.  in  a  second. 

Sound  waves  may  be  reflected  and  refracted.  In  the  ear  w^e  deal 
chiefly  with  reflections  from  curved  surfaces  in  which  the  reflection 
takes  place  on  the  opposite  side  of  the  perpendicular,  drawn  to  the 
point  of  impact  of  the  incident  wave.  The  angle  of  reflection  in- 
variably equals  the  angle  of  incidence,  and  both  occupy  the  same  plane. 
In  the  ear  we  have  curved  surfaces  which  are  constructed  in  such  a  way 
that  the  inchnations  of  the  planes  of  which  any  curved  surface  is  com- 
posed, gives  rise  to  a  convergence  of  the  sound  waves.  Thus,  the 
external  ear  of  man  possesses  a  curvature  arranged  to  reflect  these 
undulations  into  the  auditory  meatus.  The  same  is  true  of  the  ear 
trumpet  and  of  the  flexible  stethoscope.  Both  appliances  collect  the 
sovmd  waves  by  means  of  their  cup-shaped  free  ends  and  reflect  them 
into  the  meatus. 

Noises  and  Sounds. — It  is  not  always  easy  to  distinguish  between  a 
noise  and  a  sound.  In  general,  however,  it  may  be  said  that  the  former 
consists  either  of  a  brief  vibration,  as  may  be  produced  by  the  discharge 
of  a  cannon,  or  of  a  mixture  of  vibrations  as  may  be  caused  by  the 
wheels  of  a  carriage.     It  lacks,  therefore,  a  definite  wave  length  and 


758 


THE    SENSE    OF    HEARING 


regularity.  A  true  or  musical  sound  arises  in  consequence  of  a  sus- 
tained vibration,  and  possesses  an  euphonious  character  by  reason  of 
its  relatively  fixed  and  uniform  rate.  The  difference  between  noises 
and  true  sounds  may  be  well  illustrated  by  means  of  sirenes  placed  upon 
a  rotating  disc.  If  the  openings  through  which  the  air  is  blown,  are 
placed  at  regular  distances  from  one  another,  the  result  is  a  sound  of 
definite  pitch,  quahty  and  loudness,  while  if  they  are  arranged  in  an 
irregular  manner,  the  result  is  a  noise. 


Fig.  376. — Form  of  Wave  Made  by  Tuning  Fork. 

Musical  sounds  result  in  consequence  of  the  vibration  of  such 
bodies  as  strings,  rods,  plates,  bells,  membranes  and  reeds.  The  waves 
produced  by  them,  however,  do  not  affect  our  organ  of  hearing  in  a 
like  manner,  because  they  differ  from  one  another  in  their  pitch,  in- 
tensity or  loudness,  and  quality  or  timbre. 

(a)  The  pitch  or  tone  of  a  sound  is  determined  by  the  rapidity  of  vibration  of 
the  sonorous  body  and  the  number  of  undulations  produced  by  it.  The  greater 
their  number,  the  shorter  must  be  their  wave  length  and  hence,  the  higher  the 
pitch  of  the  sound.  Thus,  if  these  oscillations  recur  at  the  rate  of  500  in  a  second, 
their  time  of  vibration  is  Moo  of  a  second. 


Fig.  377. — To  Illustrate  the  Conception  of  Differences  in  Pitch  and  in  Amplitude 

OR    Intensity. 
In  A,  three  pendular  or  sinus  curves  of  the  same  period  or  pitch,  but  with  different 
amplitudes.     In  B,  three  pendular  or  sinus  curves  of  the   same   amplitude,    but  with 
different  periods.      (After  Auerbach.) 


(b)  The  intensity  or  loudness  of  a  sound  is  referable  first  of  all  to  the  amplitude 
of  the  vibrations  of  the  sonorous  body.  Thus,  if  the  bass  string  of  a  piano  is 
struck  with  slight  force,  it  will  be  seen  to  execute  a  series  of  vibrations  of  small 
amplitude,  which  give  rise  to  a  sound  of  low  audibility.  If  this  same  string  is 
then  struck  more  vigorously,  the  amplitude  of  the  vibrations  wdl  be  much  greater 
and  the  sound  much  louder.  These  changes  in  the  intensity  of  a  sound  may  also 
be  noted  as  the  vibrating  body  gradually  returns  into  its  position  of  absolute  rest. 
In  the  second  place,  the  loudness  of  a  sound  is  determined  by  the  striking  force  of 
the  waves,  because  the  latter  is  inversely  proportional  to  the  square  of  the  distance 


THE    CAUSE    AND    CHARACTER    OF    THE    SOUND    WAVES       759 

of  the  vibrator  from  the  ear  aiul  to  the  donsity  or  elastic  quality  of  the  mcdiiun. 
Thus,  the  voice  becomes  remarkably  feeble  on  top  of  a  mountain  and  is  much 
stronger  in  a  calm  atmosphere. 

((•)  The  quality,  timbre,  stamp  or  color  of  a  sound  is  the  product  of  a  variety  of 
factors;  primarily,  however,  of  the  form  of  the  movement  of  the  sonorous  body 
and  of  the  form  of  the  waves  produced  by  it.  Thus,  a  sound  of  a  certain  pitch  and 
intensity  emitted  by  a  piano,  is  (piite  different  from  that  of  a  violin  or  of  the  phonat- 
ing  organs  of  man.  If  these  .sound  waves  are  examined  more  clo.sely,  it  will  be 
found  that  they  appear  in  two  distinct  forms,  namely,  as  a  simple  or  pendular 
and  as  a  compound  or  non-pcndular  type.  If  we  permit  the  pointed  end  of  a. simple 
reed  vibrator  to  record  its  excursions  upon  the  smoked  paper  of  a  kymograph,  the 
record  so  obtained  will  show  perfectly  symmetrical  deviations  from  the  line  of 
rest,  because  the  pointer  has  swung  back  and  forth  across  the  midline  in  a  uniform 
manner.  A  compound  wave,  on  the  other  hand,  presents  a.symmetrical  deviations, 
which,  however,  may  be  perfectly  periodic. 


Fig.  378. — Schema  by  Helmholtz  to  Illustrate  the  Formation  of  a  Compound  Wave 
FROM  Two  Pendular  Waves. 
A  and  B,  pendular  \'ibrations,  B  being  the  octave  of  A.  If  superposed  so  that  e 
coincides  with  d°  and  the  ordinates  are  added  algebraically,  the  non-pendular  curve  C 
is  produced.  If  superposed  so  that  e  coincides  with  d'  the  non-pendular  curve  D  is 
produced.     {Howell.) 

Fundamental  Tones  and  Overtones. — If  the  string  of  a  musical 
instrument  is  set  into  transverse  vibration  by  plucking  it,  a  certain 
sound  will  be  emitted,  the  pitch,  quality  and  loudness  of  which  will 
depend  not  only  upon  the  length  and  the  thickness  of  this  vibrator, 
but  also  upon  the  force  with  which  it  is  displaced.  If  the  string  is 
now  firmly  held  midpoint  between  its  two  ends,  the  vibrations  of 
each  half  per  unit  of  time  will  be  doubled.  Furthermore,  if  the 
string  is  divided  in  this  way  into  three  segments,  each  division  will 
vibrate  with  a  frequency  three  times  greater  than  that  of  the  entire 


760 


THE    SENSE    OF    HEARING 


string.  Fourier  has  proved  that  every  sonorous  body,  when  made  to 
vibrate  as  a  whole,  also  exhibits  vibrations  of  its  different  segments. 
For  this  reason,  every  compound  wave  should  really  be  considered 
as  the  product  of  the  fusion  of  a  number  of  simple  waves,  i.e.,  if  a 
sonorous  body  yields,  say,  100  vibrations  in  a  second,  it  also  gives  off 
a  series  of  notes  in  the  ratio  of  1,  2,  3,  4,  etc.  The  former  give  rise 
to  the  so-called  fundamental  tone  and  the  latter  to  the  partial  tones, 
overtones  or  harmonies. 

Inasmuch  as  all  musical  instruments,  inclusive  of  the  mechanism 
set  aside  for  the  production  of  the  human  voice,  send  forth  funda- 
mental tones  as  well  as  overtones,   the   sounds   emitted   by   them. 


Fig.  379. — To    Illustr-'^.te   the    Mecilvn-ism   of   the    Form.^tiox   of   0^-ERTO^^:s. 

(Helmholtz.) 
In  a  the  string  ^-ibrates  as  a  whole,  gi^^ng  its  fundamental  tone;  in  b,  c,  and  rf,  its 
halves,  thirds  and  fourths  are  vibrating  independently.  When  a  strine  is  struck, 
plucked,  or  bowed  these  movements  may  happen  simultaneously  and  the  fundamental 
note  due  to  the  \-ibration  of  the  whole  string  is  combined  with  the  notes  due  to  the  ^■ibra- 
tions  of  aliquot  parts,  the  overtones.  The  combination  gives  a  compound  wave  whose 
form  and  musical  quality  vary  with  the  number  and  relative  strength  of  the  overtones. 

are  really  compound  in  their  nature  and  not  simple.  The  trained 
ear  is  capable  of  analyzing  these  sounds,  but  naturally,  they  arrive 
at  the  tympanic  membrane  as  compound  waves  and  are  not  separated 
into  their  component  wavelets.  In  other  words,  the  tympanic  mem- 
brane is  not  activated  by  individual  series  of  molecules  of  air  vibrating 
with  different  frequencies,  but  by  whole  waves,  the  form  of  which 
varies  in  accordance  with  their  component  wavelets. 

Reinforcement  and  Interference  of  Sound  Undulations. — If  two 
stones  are  thrown  into  the  water  at  some  distance  from  one  another,  the 
two  systems  of  wavelets  produced  around  their  points  of  contact,  fre- 


THE    CAUSE    AND    CHARACTER    OF   THE    SOUND    WAVES       761 

quently  interfere  with  one  another  so  as  to  p;ive  rise  cither  to  a  reinforce- 
ment or  a  neiitrahzation  of  the  individual  undulations.  In  quite  the 
same  manner  the  simultaneous  transfer  of  two  sounds  through  the  same 
medium  may  give  rise  to  waves  which  may  be  either  the  sum  total 
or  the  difference  of  the  two  systems  of  undulations.  The  complete 
neutralization  of  the  two  sets  necessitates,  of  course,  the  coming  to- 
gether of  the  condensed  molecules  of  one  system  with  the  rarefied 
molecules  of  the  other  system. 

If  two  tuning  forks,  the  vibrations  of  which  differ  slightly  per  unit  of 
time,  are  being  sounded  simultaneously,  the  two  systems  of  undulations 
must  interfere  with  one  another.  Consequently,  the  sound  emitted  by 
them  must  vary  from  moment  to  moment,  becoming  louder  when  they 
reinforce  and  softer  when  they  neutralize  one  another.  This  consti- 
tutes the  phenomenon  of  "beats."  If  the  difference  in  the  number  of 
vibrations  per  unit  of  time  is  increased,  the  effect  produced  on  the 
ear  becomes  increasingly  disagreeable.  The  sound  then  assumes 
a  harsh  grating  character  and  is  said  to  be  discordant  or  dissonant. 
Helmholtz  states  that  the  dissonance  assumes  an  intolerable  character, 
when  the  "beats,"  or  the  difference  in  the  vibration  frequency  of  two 
sounds,  reaches  33  to  the  second. 

In  the  absence  of  "beats"  the  general  sound  becomes  consonant  or 
harmonic.  This  implies  that  the  two  sets  of  undulations  correspond  in 
rhythm  and  amplitude,  enabling  them  to  be  combined  into  an  evenly 
balanced  compound  wave.  It  must  be  evident,  therefore,  that  a 
perfect  consonance  can  only  be  gotten  if  the  two  sets  of  waves  are 
identical  in  character.  An  almost  complete  consonance  is  also  obtained 
if  a  sound  is  elicited  in  conjunction  with  its  octave.  It  is  a  well-known 
fact  that  two  sounds  possessing  a  numerical  relationship  of  2:1,  4:1, 
etc.,  must  be  closely  allied.  Thus,  if  the  first  is  designated  as  C,  the 
second  is  called  CI,  and  the  interval  between  them  an  octave.  If  we 
now  strike  the  octave  note  of  the  second  and  then  the  octave  of  this 
one,  it  will  be  found  that  their  entire  series  of  octaves  or  eighth  notes 
become  fused  into  a  sound  which  gives  an  agreeable  sensation.  Other 
intervals  giving  consonance  are  the  following: 

1 : 2  octave 
2:3  fifth 
3:4  fourth 
4:5  major 
5 : 6  minor  third 
5:8  minor  sixth 
3:5  major  sixth 

Sympathetic  Vibration  or  Resonance. — If  the  end  of  the  handle 
of  a  vibrating  tuning  fork  is  placed  upon  a  table  or  other  elastic  body,  its 
vibrations  are  immediately  communicated  to  a  large  area  of  this 
vibrator.  Moreover,  since  the  latter  generally  vibrates  synchro- 
nously with  the  tuning  fork,  its  sound  will  be  intensified.  In  a  similar 
way,  it  is  possible  to  produce  vibrations  in  a  certain  string  of  a  piano 


762  THE    SENSE    OF.  HEARING 

by  simply  striking'a  note  of  the  same  character  upon  some  other  instru- 
ment. The  piano  answers  back  with  a  note  very  similar  to  that  re- 
ceived by  it  from  the  distance.  Also,  if  a  certain  note  is  struck  in 
the  vicinity  of  a  series  of  tuning  forks,  only  that  tuning  fork  will 
answer  which  possesses  the  same  periodicity  of  vibration  as  the  primary 
sound.  These  phenomena  are  made  possible  by  the  property  of 
sympathetic  vibration  or  vibration  of  influence.  As  has  been  pointed 
out,  the  transmission  of  the  sonorous  undulations  may  be  effected  in 
two  ways,  namely,  by  direct  contact,  and  bj^  the  transfer  of  the  waves 
through  air  without  actual  contact.  It  is  to  be  noted,  however,  that 
while  elastic  bodies  may  be  set  into  vibration  by  neighboring  bodies  and 
media,  they  cannot  be  activated  unless  their  own  periodicity  corre- 
sponds precisely  to  that  of  the  activator.  Thus,  a  string  possess- 
ing a  vibratory  quality  of  125  in  a  second,  will  not  be 
affected  by  vibrations  in  air  of  100  to  the  second. 

Helmholtz  has  devised  an  apparatus,  called  the 
resonator,  by  means  of  which  it  is  possible  to  analyze 
sounds  in  accordance  with  their  properties  of  sympa- 
thetic vibration.  It  consists  of  a  spherical  capsule  made 
of  copper  or  brass.  Its  two  opposite  sides  are  perfor- 
ated. Through  one  of  these  the  sound  is  conducted  into 
the  interior  of  the  resonator  and  from  here  through  the 
opposite  opening  into  the  external  auditory  meatus,  i 
Konig  has  introduced  an  important  modification  of  this 
appliance  by  constructing  it  of  two  hollow  cylinders.  By 
Fig.  380. —  sliding  these  telescopically  into  one  another,  the  size  of 
EoNiGs    Re-    ^j^-g  capsule  ^ay  be  either  increased  or  decreased.     If 

SONATOR.  Y  111-  1  • 

the  rubber  tube  attached  to  its  outlet  is  now  introduced 
into  the  auditory  meatus  of  one  ear  while  the  other  ear  is  closed,  the 
sounds  entering  through  the  opposite  orifice,  will  appear  stifled  with  the 
exception  of  the  one  corresponding  to  this  resonator.  This  particular 
one  sounds  out  clearly  from  among  the  confused  monotone  of  the 
others. 

If  resonators  of  varying  size  are  employed,  it  is  possible  in  this  way 
to  determine  the  presence  or  absence  of  the  different  tones  or  overtones 
represented  by  them.  Any  given  sound  may  thus  be  separated  into  its 
components.  This  power  of  analysis  is  also  possessed  by  the  auditory 
apparatus,  or  rather,  by  the  constituents  of  the  organ  of  Corti  of  the 
internal  ear.  As  Ohm  has  stated:  every  motion  of  the  air  which  cor- 
responds to  a  composite  mass  of  musical  tones,  may  be  reduced  into 
their  simple  pendular  vibrations,  and  each  single  vibration  corre- 
sponds to  a  simple  tone,  sensible  to  the  ear  and  having  a  pitch  deter- 
mined by  the  periodic  time  of  the  corresponding  motion  of  the  air. 
These  facts  suggest  that  the  organ  of  Corti  acts  in  the  manner  of  a 
resonator,  its  different  cellular  elements  being  adjusted  to  conform  to 
these  simple  vibrations.  The  manner  in  which  this  activation  is 
brought  about  will  be  discussed  in  a  succeeding  chapter. 


EXTERNAL  AND  MIDDLE  PORTIONS  OF  THE  EAR 


763 


CHAPTER  LXIII 
THE  EXTERNAL  AND  MIDDLE  PORTIONS  OF  THE  EAR 

The  Pinna  and  Auditory  Meatus. — The  organ  of  hearing  may  be 
divided  into  three  parts,  namely,  into  the  external  ear,  including  the  pinna 
or  auricle  and  auditory  meatus,  the  middle  ear,  or  tympanum,  and  the 
internal  ear,  or  labyrinth.  The  first  two  are  accessory  structures  and 
merely  serve  to  direct  the  undulations  in  air  to  the  receptor,  formed  by 
the  organ  of  Corti  of  the  cochlea.  The  pinna  or  auricle  is  the  funnel- 
shaped  expanse  of  the  auditory  meatus,  consisting  essentially  of  yellow 
elastic  tissue  covered  with  skin. 
The  cap-shaped  depression  in  its 
center  is  known  as  the  concha. 

The  external  ear  is  especially 
adapted  to  collect  the  sound  waves 
and  to  reflect  them  through  the  audi- 
tory meatus  upon  the  tympanic 
membrane.  It  may  be  taken  for 
granted,  however,  that  it  is  not  a 
particularly  important  part,  because 
many  animals  lack  the  pinna  entirely 
without  any  apparent  impairment  in 
the  acuity  of  their  hearing,  and  a 
person  whose  pinna  has  been  cut  off, 
can  hear  almost  as  well  as  previously. 
In  many  animals,  the  pinna  is  beset 
with  muscles  which  are  under  the 
control  of  the  will  and  are  employed 
to  change  its  shape  and  position  and    ,        .  ,       ,  ^        , .        ,      ^ 

...        ,,  T         ..  c    j.i_      theossicles;  5,  Eustachian  tube;  6,  vesti- 

tO    turn    it    in    the    direction    Ot    the   ^ule    of   the   internal   ear;    7,   auditory 

sound   waves.     In  many   instances, 
the    ears    are    moved    in    divergent 


F I  a .  3  81.  — Diagrammatic  Repre- 
sentation OF  THE  Different  Parts  of 
THE  Ear. 

1,  Pinna;  2,  external  auditory  meatus; 
3,  ear  drum;    4,   middle   ear   containing 


nerve;  dividing  into  two  branches,  one 

of  which  innervates  the  cochlea  and  the 

11         •         other,  the  semi-circular  canals;  8,  paro- 

directions  which  must  naturally  give  tid  gland. 
a  different  reflection  on  the  two  sides 

and  hence,  also  impart  a  different  quality  to  the  sound  as  heard  by 
the  two  ears.  This  faculty  is  especially  developed  in  horses  and  ro- 
dents. Aquatic  animals  are  in  possession  of  a  valve-like  mechanism  for 
closing  the  auditory  meatus  and  many  terrestrial  animals  are  capable 
of  enlarging  the  concha.  In  man  these  muscles  are  evidently  of  very 
little  importance,  because  they  are  retrogressive  and  cannot,  therefore, 
play  a  significant  part  in  ascertaining  the  direction  from  which  the 
sound  is  received.  The  latter  faculty  seems  to  originate  in  the  con- 
jugate deviation  of  the  eyes  toward  the  side  from  v/hich  the  sound 
waves  have  been  projected. 


764  THE    SENSE    OF    HEARING 

The  external  auditory  meatus  of  man  is  a  tubular  passage  21-26 
mm.  in  length,  8-9  mm.  in  height,  and  6-8  mm.  in  width.  It  pursues  a 
slight  spiral  course  forward,  inward  and  upward,  but  may  be  straight- 
ened very  easily  by  pulling  the  pinna  upward  and  backward.  This 
is  made  possible  by  the  fact  that  the  wall  of  this  canal  is  cartilaginous 
and  movable  for  a  distance  of  about  one-half  inch,  while  internally  to 
this  point  it  becomes  osseous.  The  delicate  skin  lining  this  canal 
contains  numerous  sebaceous  and  ceruminous  glands  which  furnish 
the  cerumen,  a  yellowish  wax-like  secretion,  possessing  a  bitter  taste 
and  peculiar  odor.  This  secretion  is  lubricating  and  protective  in 
its  function,  because  it  prevents,  in  conjunction  -ndth  the  hairs,  the 

entrance  of  dust  and  larger  foreign 
particles.  Its  excessive  formation 
and  subsequent  drying  frequently 
lead  to  the  formation  of  chips  and 
plugs  which  greatly  impair  the  pas- 
sage of  the  sound  waves,  thereby 
diminishing  the  acuity  of  hearing. 

The  Middle  Ear  or  Tjonpanum. 
— The  middle  ear  consists  of  an  ir- 
regular cavity  hollowed  out  of  the 
petrous  portion  of  the  temporal  bone. 
It  is  broader  above  and  behind  than 
below  and  in  front,  and  is  shut  off 
„  „  from  the  external  auditory  meatus 

Fig.  3  8  2. — Dl\grammatic    Repre-   ,        ,,  , 

sENTATioN  OF  THE  iMiDDLE  K^R  OR  Tym-  ^y  thc  eardrum  or  tympanic   mem- 

PANic  Cavity.  brane.     Anteriorly,  it  communicates 

1,  External  auditory  meatus;  2,  the  with   the  pharynx   by  means  of  a 

ear    drum    or   tympanic    membrane;    3,  i  i  au         u-i,*i 

malleus,    with    its    manubrium    resting  long  and  narrow  tube  whlch  IS  knOWn 

against   the   internal   surface  of  the  ear  as    the    Eustachian    tube,  while    pOS- 

drum;  4,  incus;  5  stapes  resting  against  ^gj,iQj.ly      J^     Jg     connected    with    the 
the  membrane  of  the   fenestra  ovalis;  6,  i  x  c  ti 

vestibule  of  the  internal  ear;  7,  fenestra  COmpleX    Systcm    of  Small  CaVltlCS  in 

rotunda;  8,  Eustachian  tube;  9,  saccule;  the    mastoid     bone,     knOwn    aS    the 

10,     central    canal    of  the    cochlea;    11.  m^stoid    antrum    and    mastoid    Cclls. 
utricle;  12,  muse,  tensor  tvmpani.  .  .  .    ,      .       „ 

Its  inner  wall,  which  is  formed  by 
the  bony  septum  of  the  internal  ear,  is  perforated  in  two  places.  In- 
asmuch as  one  of  these  openings  is  oval  in  shape  and  the  other  round, 
they  are  designated  as  the  fenestra  ovahs  and  fenestra  rotunda.  Both 
are  closed  by  a  membrane,  the  outer  surface  of  which  lies  in  contact 
with  the  air  of  the  tj^mpanum,  while  theu*  inner  surface  borders  upon 
the  lymphatic  fluid  filUng  the  labyrinthine  spaces.  The  tympanic  cav- 
ity is  occupied  by  three  small  bones  known  as  the  ossicles,  which  are 
arranged  in  series  between  the  inner  surface  of  the  eardrum  and  the 
outer  surface  of  the  membrane  closing  the  fenestra  ovahs.  These  os- 
sicles are  freely  suspended  in  this  space  and  are  held  in  position  by 
ligamentous  bands  attached  to  different  points  of  the  wall,  as  well  as 


EXTERNAL    AND    MIDDLE    PORTIONS    OF    THE    EAR 


765 


bj^  two  muscles,  known  as  the  muse,  tensor  tympani  and  the  muse, 
stapedius. 

The  Tympanic  Membrane  or  Eardrum. — The  tympanic  membrane 
is  stretclied  across  a  cartilaginous  ring  which  is  placed  obliquely  in 
the  inner  end  of  the  auditory  canal.  It  possesses  a  somewhat  oval 
shape  and  is  tilted  at  an  angle  of  40°  in  a  direction  from  above  and  with- 
out to  a  point  within  and  below,  this  peculiarity  in  its  position  en- 
abling it  to  present  a  much  larger  surface  to  the  sound  waves.  The 
membrane  itself  is  9.5-10  mm.  in  length  and  8  mm.  in  breadth.  Its 
thickness  measures  0.1  mm.  and  its  area  50  mm.  It  consists  of  three 
layers,  its  middle  coat  being  formed  of  fibrous  tissue  which  is  en- 
veloped externally  by  a  delicate  layer  of  skin,  and  internally  by  the 
mucous  membrane,  lining  the  general  cavity  of  the  tympanum.  The 
fibers  of  the  median  coat  are  chiefly  arranged  in  a  radial  direction, 


Membrana  flaccida        Posterior  ligament 


Anterior  ligament  — -, 


—  Long  process  of  incus 


-  End  of  manubrium  of  malleus 


Fig.  38.3. — Membrana  Tympani,  as  Seen  with  the  Otoscope.      (Heusman.) 


but  some  of  them  are  also  adjusted  circularly  around  its  center.  The 
latter  are  especially  numerous  in  the  region  where  this  membrane  is 
joined  to  the  ring  of  cartilage. 

The  inner  surface  of  the  eardrum  lies  in  contact  with  the  handle, 
or  manubrium,  of  the  first  ossicle,  commonly  known  as  the  hammer- 
bone  or  malleus.  This  process  is  securely  fastened  to  its  median 
layer,  the  membrana  propria,  by  an  overlapping  of  its  circular  fibers. 
When  observed  through  the  external  meatus,  the  line  of  contact  be- 
tween the  malleus  and  the  eardrum  is  sharply  outlined  by  an  opaque 
ridge  which  commences  near  its  upper  anterior  margin  and  extends 
downward  and  backward  to  a  point  slightly  below  its  center.  The 
surface  of  the  eardrum  is  not  flat,  but  convex  toward  the  outside.  Its 
apex  points  inward,  this  central  depression,  or  umbo,  being  caused  by 
the  inward  traction  of  the  tip  of  the  manubrium.  It  will  be  seen, 
therefore,  that  the  different  radial  fibers  uniting  this  process  with  the 
membrane,  are  arranged  as  arches  around  a  common  center. 


766 


THE    SENSE    OF    HEARING 


It  need  scarcely  be  emphasized  that  the  external  auditory  meatus 
plays  the  part  of  a  tube  tending  to  conserve  the  character  of  the  sound 
waves.  They  are  deflected  from  its  walls  into  the  pit  of  the  funnel- 
shaped  tympanic  membrane,  but  since  the  sides  of  the  latter  are 
convex,  their  amplitude  must  be  diminished,  while  their  striking  force 
is  increased.  In  this  way,  this  membrane  is  set  into  vibration  in 
complete  harmony  with  the  undulations  in  the  air.  Moreover,  since  it 
is  small  in  size,  it  is  able  to  move  as  one  whole  and  with  a  definite  perio- 
dicity. The  latter  peculiarity  is  of 
particular  value,  because  it  prevents 
the  magnification  of  certain  overtones 
to  the  exclusion  of  others.  In  addi- 
tion, its  structure  and  position  are 
such  that  it  is  able  to  offer  a  certain 
resistance  to  the  oscillations  of  this 
system  which  causes  the  latter  to 
cease  almost  as  soon  as  the  sound 
has  been  completed.  The  dampen- 
ing effect  is  of  great  functional  im- 
portance, because  it  keeps  these  parts 
in  a  state  of  readiness  to  receive  new 
vibrations. 

The  Ear  Bones  or  Ossicles. — The 
connection  between  the  eardrum  and 
the  membrane  of  the  fenestra  ovalis 
is  formed  by  three  bones  which  are 
known  as  the  malleus,  incus,  and 
stapes. 


Fig.    384. — View    of    the    Mem- 

BHANA  TtMPANI  AND  AuDITORY  OS- 
SICLES FROM  THE  Inner  Side. 
{Schafer.) 

m,  Malleus;  i,  incus;  st,  stapes;  py, 
pyramid,  from  which  the  tendon  of  the 
stapedius  muscle  is  seen  emerging;  U, 
tendon  of  the  tensor  tympani  cut 
short  near  its  insertion;  la,  anterior 
ligament  of  the  malleus;  the  anterior 
process  (processus  gracilis)  is  concealed 
by  the  lower  fibers  of  this  ligament;  Is, 
superior  ligament  of  the  malleus;  li, 
ligament  of  the  incus;  ch,  chorda  tym- 
pani nerve  passing  across  the  outer 
wall  of  the  tympanum. 


The  malleus  or  hammer  bone,  is  8-9 
mm.  in  length  and  possesses  an  average 
weight  of  23  mgrs.  It  consists  of  a  rounded 
head,  grooved  on  one  side  for  its  articulation 
with  the  incus,  a  short  massive  neck  and  a 
long  handle,  or  manubrium.  The  latter  is 
securely  fastened  in  the  tissue  of  the  eardrum 
and  presents  two  processes,  one  of  which  is 
known  as  the  processus  brevis  and  the  other 
as  the  processus  gracilis.  The  former  presses 
against  the  eardrum  above  the  umbo,  while  the  latter  extends  into  the  Gasserian 
fissure  in  the  wall  of  the  tympanum.  The  malleus  is  held  in  place  by  three  liga- 
ments, a  superior,  anterior  and  posterior.  The  first  of  these  holds  the  head  of 
this  bone  against  the  roof  of  the  tympanic  cavity,  while  the  second  and  third 
secure  its  neck  in  a  position  near  the  anterior  wall  of  this  space.  Besides  serving 
as  supports,  these  ligaments  also  force  this  bone  to  rotate  around  a  perfectly  definite 
axis.  This  is  true  especially  of  the  anterior  and  posterior  ligaments  which  tend 
to  fix  its  neck  portion  as  if  it  were  placed  in  a  sling.  Consequently,  the  inward 
movement  of  the  eardrum  and  manubrium  must  cause  the  head  of  this  bone  to 
move  outward,  while  their  outward  movement  must  force  the  latter  inward. 

The  incus  or  anvil  bone,  weighs  about  25  mgrs.  and  possesses  a  shape  somewhat 
similar  to  that  of  a  bicuspid  tooth,  its  heavier  upper  portion  being  hollowed  out  for 


EXTERNAL  AND  MIDDLE  PORTIONS  OF  THE  EAR     767 

the  reception  of  the  head  of  the  malleus.  This  articulation  is  cfTocted  in  a  plane 
situated  somewhat  al)ove  the'  l)iim  of  the  eardrum.  This  ossicle  presents  two 
processes,  the  largest  of  which  measures  4.5  mm.  and  the  otiier3.0  mm.  in  length. 
To  begin  with  the  former  extends  downward,  parallel  to  the  manul)rium  of  the 
malleus,  but  suddenly  turns  inward  to  enter  into  articulation  with  the  stapos. 
The  short  process  is  fastened  to  the  posterior  wall  of  the  tympanum  by  a  thick 
ligament  which,  however,  gives  rise  to  only  a  partial  fixation  of  this  bone. 

The  stnpci^  or  stirrup  bone,  is  only  2.5  mm.  in  length  and  weighs  about  3  mgrs. 
Its  base  is  oval  in  shape  and  is  fastened  to  the  membrane  of  the  fenestra  ovalis  by 
means  of  a  number  of  radial  fibers  of  connective  tissue.  This  foramen  measures 
3  mm.  in  length  and  15  mm.  in  width. 

The  Movements  of  the  Ossicles. — It  need  scarcely  be  emphasized 
that  the  function  of  the  ear  bones  is  to  convert  the  vibrations  of  the 
eardrum  into  vibrations  of  the  membrane  closing  the  fenestra  ovalis. 
This  implies  that  the  undulations  in  air  are  converted  into  oscillations 
of  the  lymphatic  fluid  filling  the  spaces  of  the  internal  ear.''  The 
latter  then  activates  the  constituents  of  the  organ  of  Corti.  In  endeav- 
oring to  analj^ze  the  action  of  the  ossicles  it  must  be  remembered  that 
the  manubrium  of  the  malleus  is  firmly  anchored  to  the  eardrum  and 
must,  therefore,  move  in  harmony  with  the  latter.  This  fact  may  be 
demonstrated  in  a  very  convincing  manner  by  placing  the  umbo  under 
the  ocular  of  a  microscope, ^  inserted  through  a  perforation  in  the 
upper  wall  of  the  tympanum.  When  measured  with  the  help  of  a 
micrometer,  these  movements  are  seen  to  attain  a  maximal  ampUtude 
of  about  0.2  to  0.7  mm. 

Inasmuch  as  the  neck  of  the  malleus  is  fixed  by  the  anterior  and 
posterior  ligaments,  the  inward  movement  of  its  manubrium  must  give 
rise  to  an  outward  deviation  of  its  caput.  This  simple  pendular 
motion,  however,  cannot  become  excessive,  because  the  malleus 
executes  at  the  same  time  a  rotatory  movement  around  its  long  axis. 
The  outward  inclination  of  the  caput  of  the  malleus  in  turn  enforces 
a  movement  of  the  head  of  the  incus  in  the  same  direction.  At  this 
very  moment  the  latter  is  turned  as  a  whole  around  the  axis  formed  by 
its  short  process,  while  its  long  process  is  raised  and  is  forced  inward 
against  the  stapes,  pushing  the  latter  more  deeply  into  the  foramen 
ovale.  The  outward  movement  of  the  eardrum  produces  a  movement 
of  these  ossicles  in  the  opposite  direction.  Helmholtz  has  compared 
the  malleus-incus  articulation  to  the  joints  of  a  Breguet  watch-key, 
possessing  a  row  of  interlocking  teeth  which  force  the  stem  of  the  watch 
in  one  direction,  but  prevent  its  revolution  in  the  opposite  direction. 

It  will  be  seen,  therefore,  that  this  series  of  bones  acts  in  the 
manner  of  a  bent  lever,  the  fulcrum  of  which  is  placed  at  the  tip  of  the 
short  process  of  the  incus,  while  the  power  arm  extends  from  here 
through  the  tip  of  the  manubrium,  and  the  load  arm,  from  here  through 
the  tip  of  the  long  process  of  the  incus.     This  arrangement  is    repre- 

1  Helmholtz,  Pfiuger's  Archiv,  i,  1869,  34. 

2  GoUtzer,  Archiv  f i\r  Ohrenheilkunde,  i,  1864,  59,  also  see :  Mach  and  Kessel, 
Ber.,  Akad.  der  Wissensch.,  Wien,  Ixix,  1874,  221. 


768  THE    SENSE    OF    HEARING 

sented  in  the  adjoining  diagram  (Fig.  385).  WTien  combined  into  one 
single  mass,  these  bones  act  upon  the  axis  a-b,  the  manubrium  c 
and  stapes  d  then  pursuing  precisely  the  same  course,  inward  as  well  as 
outward  (Fig.  386).  This  system  is  rendered  especially  sensitive  by 
the  fact  that  a  large  part  of  the  total  mass  of  the  malleus  and  incus 
comes  to  lie  above  their  axis  of  rotation  a-b,  so  that  their  upper  por- 
tions are  made  to  act  as  a  counterpoise  for  the  parts  situated  below 
this  axis.  The  latter  constitute  the  real  lever,  sensitized,  as  has  just 
been  stated,  by  this  counterpoising  weight.  It  should  be  noted,  how- 
ever, that  the  oscillations  of  the  stapes  possess  a  smaller  amplitude 
than  those  of  the  eardrum,  the  relationship  between  them  being  as 


Fig.  385,  Fig.  386. 

Fig.  385. — To  Illustrate  the  Lever  Action  of  the  Ear  Bones. 

M,  the  malleus;  e,  the  incus;  a-b,  the  axis  of  rotation;  a,  short  process  of  incus  abut- 
ting against  the  tympanic  wall;  a-p,  the  power  arm;  a-r,  the  load  arm  of  the  lever. 
(McKendrick.) 

Fig.  386. — Schema  to  Illustrate  the  Way  in  Which  the  Ear  Ossicles  Act  To- 
gether AS  a  Bent  Levxr  in  Transmitting  the  Mo\'ements  of  the  Tympanic  Membran-e 

TO  THE  MeMBR.\N'E  OF  THE  FENESTRA  OVALIS. 

1,  The  handle  of  the  malleus;  2,  the  long  process  of  the  incus;  3,  the  stapes;  a-b,  the 
axis  of  rotation.  The  arrows  indicate  a  movement  inward  of  the  tympanic  membrane. 
(Hoivell.) 

0,04  mm.  to  0.4  mm.  The  force,  however,  with  which  they  strike 
against  the  fenestra  ovalis,  is  increased  in  the  proportion  of  2  to  3, 
because  the  length  of  the  arms  of  the  lever  formed,  on  the  one  hand,  by 
the  manubrium,  and,  on  the  other,  by  the  long  process  of  the  incus,  is 
as  3  to  2.  Furthermore,  since  the  area  of  the  eardrum  is  about  twenty 
times  as  large  as  that  of  the  membrane  closing  the  foramen  ovale, 
the  initial  energy  is  concentrated  in  this  way  upon  an  area  twenty 
times  smaller  than  that  exposed  to  the  sound  waves.  Consequently, 
the  force  of  these  waves  is  augmented  %  X  20  =  30  times,  when  pro- 
jected against  the  fenestra  ovalis. 

It  is  also  of  importance  to  remember  that  this  system  is  not  given 
to   after-vibration,   because  it  is  made  to  act  under  a  considerable 


EXTERNAL    AND    MIDDLE    PORTIONS    OF    THE    EAR  709 

resistance  which  finds  its  ()ii«i;in  in  sovci'al  conthtioiis.  Arnonp;  these 
we  have  cited  the  pecuUarities  in  the  .structun-  antl  jxjsition  of  the  eur- 
drum  and  also  the  unusual  characteristics  of  the  lever  formed  by  the 
ossicles.  In  addition,  Hehnholtz  has  called  attention  to  the  fact  that 
the  articulation  l)ct\vccn  Ihc  malleus  and  incus  may  be  broken  at  any 
time  by  unusually  strong  inward  movements  of  the  eardi-um.'^  The 
head  of  the  malleus  is  then  forced  outward  so  far  that  the  incus  cannot 
follow  it.  Doubtlessly,  this  dislocation  serves  to  protect  the  internal  ear 
against  sounds  of  extraordinary  striking  force.  As  we  shall  see  later, 
an  additional  factor  of  safet}^  has  been  provided  in  the  shape  of  the 
stapedius  muscle,  the  contraction  of  which  pulls  the  head  of  the  stapes 
over  so  that  this  bone  presses  more  firmly  upon  the  membrane  closing 
the  fenestra  ovalis,  thereby  diminishing  its  vibratory  qualities. 

The  Eustachian  Tube. — A  membrane,  such  as  the  eardrum,  is 
capable  of  developing  the  most  perfect  vibrations  only  when  the  pres- 
sure upon  its  two  surfaces  is  equal.  If  the  tympanic  cavity  were 
absolutely  closed,  the  air  contained  therein  would  be  absorbed  in  the 
course  of  time,  establishing  a  rarefaction  which  in  turn  would  give  rise 
to  an  inward  bulging  of  the  eardrum,  and  a  diminution  in  its  oscillatory 
power.  Under  ordinary  conditions,  however,  a  result  of  this  kind 
is  obviated  by  the  fact  that  the  tympanum  is  connected  with  the 
pharyngeal  cavity  by  means  of  a  membranous  communication,  known 
as  the  Eustachian  tube.  While  the  pharyngeal  end  of  this  channel 
is  kept  closed  under  ordinary  conditions,  it  may  be  opened  at  any  time 
by  the  act  of  swallowing  which  involves  a  contraction  of  the  muse,  tensor 
veil  palatini.  This  permits  of  an  interchange  of  air  in  both  directions. 
The  closure  of  this  orifice  results  immediately  upon  the  cessation 
of  this  muscular  effort  on  account  of  the  elastic  recoil  of  its  valve-like 
lips,  situated   inside  the  ostium. 

If  we  enter  a  tunnel  in  which  the  pressure  is  above  that  of  the 
atmospheric  air,  the  tympanic  membrane  is  forced  inward.  This  gives 
rise  to  a  peculiar  local  sensation  of  pressure  as  well  as  to  a  diminution 
in  the  acuity  of  hearing.  The  tube  is  then  opened  by  the  act  of 
swallowing  which  allows  the  required  amount  of  air  to  rush  into  the 
tympanum.  In  a  similar  way,  a  diminution  in  the  atmospheric  pres- 
sure gives  rise  to  an  outward  displacement  of  the  eardrum  which  is 
remedied  immediately  by  permitting  air  to  escape  from  the  tympanum. 
A  condition  of  the  first  kind  may  be  set  up  very  easily  by  swallowing 
during  the  act  of  inspiration  while  the  lips  and  nostrils  are  held  shut. 
The  opposite  condition  may  be  produced  by  swallowing  during  expira- 
tion while  the  lips  and  nostrils  are  kept  closed. 

Although  this  tube  serves  chiefly  as  a  means  for  the  ventilation 
of  the  tympanum,  it  also  forms  a  natural  outlet  for  excess  secretions. 
Both  functions  are  greatly  impaired  duiing  catarrhal  affections  of  the 

1  This  hypothesis  has  been  criticized  by  von  Frey  (Pfliigcr's  Archiv,  cxxxLx,  1911, 
548)  upon  the  ground  that  the  malleus  and  incus  are  not  united  by  a  true  joint, 
but  are  more  or  less  ankylosed. 

49 


770 


THE    SENSE    OF    HEARING 


pharynx  involving  this  tube,  as  may  be  gathered  from  the  diminution 
in  the  acuity  of  hearing  then  commonly  experienced.  In  many  in- 
stances, these  simple  catarrhal  affections  pave  the  way  for  suppurative 
processes  which  spread  from  the  lining  of  the  tympanum  to  the  ossicles, 
destroying  them  in  part  or  causing  them  to  become  ankylosed.  The 
exudations  formed  in  the  course  of  this  process  most  commonly  burrow 
their  way  through  the  eardrum,  but  without  permanently  destroying 
the  oscillatory  qualities  of  this  membrane.  The  greatest  danger  of 
an  infection  of  this  kind  lies  in  the  fact  that  it  may  spread  to  the 
adjoining  mastoid  cells  and,  unless  the  latter  are  freely  drained, 
give  rise  to  a  septic  infection  of  the  neighboring  meninges. 

The  Inherent  Muscles  of  the  Ear. — Besides  the  different  muscles 
attached  to  the  pinna,  the  ear  also  contains  two  muscles  which  are 
intimately  concerned  with  the  transmission  of  the  sound  waves  through 
the  tympanum.  These  muscles  are  the  tensor  tympani  and  the 
stapedius.  The  former  is  placed  in  a  long  furrow  above  the  Eustachian 
tube  and  is  inserted  by  means  of  a  long  tendon 
into  the  neck  of  the  malleus  directly  below  the 
axis  of  rotation  of  this  bone.  It  is  innervated 
by  fibers  derived  from  the  trigeminus  and  re- 
legated to  the  otic  ganglion.  When  this  muscle 
contracts,  it  pulls  the  eardrum  inward,  thereby 
placing  it  under  a  greater  tension.  This  ful- 
fills two  purposes,  namely  to  accommodate  the 
drum  to  sounds  of  higher  pitch,  and  to  lessen 
its  vibratory  power  whenever  sounds  of  great 
intensity  are  received.  It  need  scarcely  be 
mentioned  that  a  sound  of  high  pitch  can  only 
be  transferred  in  its  true  form  if  the  tension  of 
the  drum  is  increased  sufficiently  to  correspond 
to  its  wave-length.  In  the  second  place,  it 
must  be  evident  that  a  tense  membrane  is  more 
resistant  than  a  flaccid  one  and  cannot,  there- 
fore, be  made  to  vibrate  so  easily.  For  this  reason,  the  tensor  tympani 
muscle  may  also  be  regarded  as  a  protective  means  against  the  activa- 
tion of  the  organ  of  Corti  by  sounds  of  unusual  intensity.  Conse- 
quently, its  function  is  very  similar  to  that  of  the  iris  which,  by  the 
contraction  of  its  radial  fibers,  lessens  the  size  of  the  pupil,  thereby 
preventing  the  entrance  of  a  bundle  of  light  of  injurious  intensity  to 
the  retina. 

The  stapedius  muscle  arises  from  the  inner  wall  of  the  tympanum 
near  the  fenestra  ovalis.  Its  tendon  passes  forward  and  is  inserted 
upon  the  posterior  aspect  of  the  neck  of  the  stapes.  On  contraction 
it  pulls  this  bone  over  in  a  lateral  direction  so  that  the  hinder  part 
of  its  base  is  pressed  more  firmly  into  the  membrane  closing  this 
foramen.  In  accordance  with  the  degree  of  its  deviation,  it  increases 
the  tenseness  of  this  membrane  until  its  vibration  is  finally  prevented 


Fig 


Diagram  Il- 


lustrating THE  Action  of 
THE  Stapedius  Muscle. 

A,  state  of  relaxation; 
B,  state  of  contraction;  s, 
stapes;  m-s,  muse,  sta- 
pedius. 


THE    INTERNAL    EAR    OR    LABYRINTH  771 

altogether.  The  stapedius  muscle,  therefore,  serves  the  same  purposes 
as  the  tensor  tympani,  i.e.,  it  accommodates  the  membrane  of  the  fen- 
estra ovalis  to  high  sounds,  and  prevents  those  of  unusual  intensity  from 
reaching  the  internal  ear.  The  motor  fibers  of  this  muscle  are  derived 
from  the  facial  nerve. 

Both  muscles  react  in  consequence  of  reflex  stimuli  which  appear 
to  be  derived  from  the  auditory  nerve,  ^  whence  they  are  transferred 
in  the  medulla  to  the  aforesaid  motor  paths.  These  stimuli  arise  at 
the  very  beginning  of  the  different  sounds  and  subject  these  membranes 
to  constant  changes.  Some  persons  are  capable  of  contracting  the 
tensor  tympani  voluntarily.  ^ 


CHAPTER  LXIV 
THE  INTERNAL  EAR  OR  LABYRINTH 

General  Structure. — The  general  cavity  of  the  internal  ear,  or 
osseous  labyrinth  is  hollowed  out  of  the  petrous  portion  of  the  tem- 
poral bone.  It  consists  of  three  parts,  namely,  the  vestibule,  the 
semicircular  canals  and  the  cochlea.  It  is  lined  throughout  with  thin 
periosteum.  This  entire  space  is  filled  with  a  lymphatic  fluid,  called 
the  perilymph.  Suspended  in  this  fluid  is  a  membranous  reproduction 
of  the  osseous  labyrinth,  which  in  turn  is  filled  with  a  lymphatic 
fluid,  called  the  endolymph.  The  outer  surface  of  the  latter  keeps  at 
varying  distances  from  the  wall  of  the  bony  cavity.  The  space  be- 
tween them  is  occupied  by  perilymph  and  is  transected  by  ligamentous 
bands  and  fibers  which  hold  the  membranous  labyrinth  in  place.  In 
the  vestibular  part  of  the  osseous  labyrinth,  this  membranous  tube 
shows  two  enlargements  which  are  known  respectively  as  the  utricle 
and  saccule.  The  former  is  directly  continuous  with  the  membranous 
tubes  of  the  semicircular  canals  and  the  latter,  with  the  membranous 
canal  of  the  cochlea. 

It  will  be  brought  out  later  on  that  the  semicircular  canals  are  con- 
cerned solely  with  the  sense  of  equilibrium,  while  the  cochlea  mediates 
the  sense  of  hearing.  For  the  present,  therefore,  we  must  confine  our- 
selves to  a  study  of  the  latter  structure.  The  cavity  of  the  internal 
ear  is  separated  from  that  of  the  tympanum  by  a  bony  wall,  which  is 
perforated  in  two  places  to  form  the  fenestra  ovaHs  and  the  fenestra 
rotunda.  Both  openings  are  closed  by  membranes,  the  outer  surfaces 
of  which  lie  in  contact  with  air,  while  their  inner  surfaces  border  upon 
the  perilymph  of  the  labyrinth.  It  has  also  been  pointed  out  that  the 
vibrations  in  air  are  eventually  converted  into  vibrations  of  lymph  at 

^  Henson,  Pflliger's  Archiv,  Ixxxvii,  1901,  355. 
''  Mangold,  Pflliger's  Archiv,  cxlix,  1913,  539. 


772 


THE    SENSE    OF   HEARING 


the  fenestra  ovalis.  From  here  these  oscillations  spread  throughout 
the  perilymph  of  the  vestibule  and  pass  toward  the  semicircular  canals 
as  well  as  toward  the  cochlea.  In  most  cases,  however,  they  fail 
absolutely  in  activating  the  sense-organs  of  equilibrium  in  the  utricle 
and  ampullae  of  these  canals,  because  the  latter  do  not  lie  in  the  direct 
course  of  these  waves,  and  are  not  specifically  adapted  to  them.  The 
cochlea,  on  the  other  hand,  turns  its  funnel-shaped  basal  portion 
directly  toward  the  vestibule  and  into  the  path  of  these  oscillations. 

Besides,  this  structure  gives  lodg- 
ment to  the  sense-organ  which  is 
specifically  set  aside  for  their  recep- 
tion. 

The  Osseous  Canal  of  the 
Cochlea. — The  central  chamber  of 
the  labyrinth,  or  vestibule,  measures 
5  mm.  in  diameter  and  communicates 
anteriorly  with  the  cochlea.  The 
latter  is  a  cone-shaped  structure, 
measuring  9  mm.  across  at  its  base, 
and  5  mm.  from  its  base  to  its»apex. 
The  tip  or  cupola  of  the  latter  is  di- 
rected outward  and  slightly  forward 
V^^k^*''^llM|||r^^  and  downward.     It  contains  a  canal 

2,  ^^^^^l^^^^i™^  which  is  twisted  upon  itself  two  and 

^^HBMIH^^H^^    one-half  times  in  the  manner  of  the 

shell  of  a  snail.  This  canal  measures 
about  33  mm.  in  length.  It  is 
largest  at  its  base,  where  it  measures 
about  2  mm.  in  diameter.     The  cen- 

the  internal  ear  (perilymph);   6,  utricle;  ^j-^l    core    arOUnd  which  it  is  WOUnd, 

7,   central  canal  of  the  cochlea;  8,   scala  .       ,  ,  ,.    ,  rru 

vestibuli;   9,  saccule;  10,  endolymphatic  IS     knOWn     aS     the     modiolus.         The 

duct    between    saccule   and   utricle;    11,  latter    COnsistS    of    a    Central    Spongy 

ampulla  of  semicircular  canal;  12,  canalis  portion  which  is  pierced  by  a  tube 
reumens;  13,  scala  tympam;  14,  helico-        .,,      .^  .  n    ,         i       /•         .i 

trema;  15,  fenestra  ovalis.  With    its    VariOUS    collaterals    for    the 

reception  of  blood-vessels  and  the 
fibers  of  the  cochlear  branch  of  the  auditory  nerve.  A  bony  plate, 
the  lamina  spirahs,  projects  from  this  central  mass  of  bone  almost 
horizontally  into  the  lumen  of  the  cochlear  canal,  winding  round  into 
its  tip  in  the  manner  of  a  circular  staircase.  It  partially  divides  the 
lumen  of  this  canal  into  two  compartments  or  scalse;  this  division  be- 
ing made  complete  by  a  membranous  septum  which  stretches  straight 
across  from  the  end  of  the  bony  lamina  to  the  opposite  wall  of  the 
canal.  This  is  the  so-called  basilar  membrane.  Below  the  latter,  we 
have  the  scala  tympani  and  above  it,  the  scala  vestibuli.  The  cochlear 
canal  as  a  whole  is  placed  in  such  a  way  that  its  vestibular  scala  faces 
the  foramen  ovale,  while  its  tympanic  scala  is  directed  toward  the 
foramen    rotundum.     These    tubes  communicate  with  one  another 


Fig.  388. — Diagrammatic  View  of  the 
Internal  Ear. 
1,    Tympanic  cavity;  2,  Eustachian 
tube;  3,  incus;  4,  stapes;  5,  vestibule  of 


THE    INTERNAL    EAR    OR    LABYRINTH 


773 


through  a  small  orifice  in  the  tip  of  the  cochlea,  which  is  known  as 
the  helicotrenia. 


9 


YiG.  389. — Membranous  Labyrinth  of  the    Right  Side,    Seen  from  the   External 

Surface. 

1,  Utricle;  2,  superior  semicircular  canal;  3,  posterior  semicircular  canal;  4,  external 
semicircular  canal;  5,  saccule;  6,  endolymphatic  canal,  with  7  and  7',  its  two  branches, 
and  8,  its  vestibular  cul-de-sac;  9,  cochlear  canal,  with  9',  its  vestibular  and  9",  its 
terminal  cul-de-sac;  10,  canalis  reuniens  of  Hansen.  (American  Text-book  of  Physio- 
logy.) 

These  two  scalae,  therefore,  are  separate  tubes.  The  scala  vestibuli 
ascends  from  the  vestibule  into  the  tip  of  the  cochlea,  while  the  scala 


Fig.  390.  Fig.  391. 

Fig.  390. — Cross-section  Through  the  Cochlea,  Showing  the  Different  Win-dings 

OF  THE  Canals. 
M,    modiolus,  with  the  branches  of  the  cochlear  division  of  the  auditory  nerve; 
S,  spiral  ganglion;  b,  basilar  membrane  with  the  organ  of  Corti;  s-v,  scala  vestibuli; 
s-t,  scala  tympani;  c,  central  canal. 

Fig.  391. — Dlagram   Illustrating    the  Vibration    in    Opposite    Directions  of  the 
Membrant:s  Closing  the  Fenestra  Ovalis  and  Rotun-da. 
S,  stapes;  o,  fenestra  ovalis;  r,  fenestra  rotunda. 

tympani    descends    from   here   to   the   fenestra   rotunda.     Both   are 
filled  with  perilymph,  and  the  vibrations  set  up  by  the  oscillations 


774 


THE    SEXSE    OF    HEARING 


of  the  stapes  are  propagated  through  them  in  the  direction  from  the 
vestibule  to  the  fenestra  rotunda.  This  is  of  importance,  because  it 
enables  the  membranes  closing  the  aforesaid  foramina,  to  vibrate  in 
unison.     In  other  words,  an  inward  movement  of  the  membrane  of 


ir4 


Fig.  392. — Di.\gr.\m  of  a  Tr.^xs-\-erse  Section-  of  the  Cochlea. 
Sc.V,  scala-vestibuli;  Sc.T,  scala  tympani;  C.Chl,  canalis  cochlearis;  Lam.sp,  lamina 
spiralis;  Gg.sp,  ganglion  spirale;  n.aud,  auditory  nerve;  m.R,  membrane  of  Reissner; 
Str.v,  stria  vascularis;  Lg.sp.  ligamentum  spirale;  /./,  lymphatic  epithelioid  lining  of 
basilar  membrane  on  the  tympanic  side;  m.b,  basilar  membrane;  Org.  C,  organ  of  Corti; 
L.t,  labium  tympanicum;  lb,  limbus;  L.v,  labium  vestibulare;  /n.t,  tectorial  membrane. 
(After  Foster.) 


the  fenestra  ovalis  gives  rise  to  an  outward  movement  of  the  mem- 
brane of  the  fenestra  rotunda.  If  no  provision  had  been  made  for  this 
interchange  of  pressure  within  the  internal  ear,  the  membrane  of  the 


THE    INTERNAL    EAR    OR    L.VBVRINTH  775 

fenestra  ovalis  could  not  vibrate  properly,  because  it  could  not  over- 
come the  hi<j;h  resistance  resident  in  this  chanil^er. 

The  Membranous  Canal  of  the  Cochlea. — It  has  just  been  shown 
that  the  osseous  canal  of  the  coclilca  is  bisected  by  the  spiral  lamina 
and  the  basilar  membrane  attached  thereto.  Directly  above  the 
meml)ranous  part  of  this  partition,  a  second  membrane  stretches  ob- 
liquely across  the  lumen  of  the  vestibular  scala  which  thus  cuts  off  an 
angular  space,  known  as  the  central  canal  of  the  cochlea  or  scala  media. 
The  lower  boundary  of  the  latter  is  formed  by  the  basilar  membrane 
(lamina  basilaris),  its  outer  boundary  by  the  bony  wall  of  the  cochlea, 
and  its  upper  by  the  aforesaid  membrana  vestibularis  or  membrane  of 
Reissner.  This  space  is  filled  with  endolymph  and  forms,  there- 
fore, the  cochlear  continuation  of  the  membranous  labyrinth.     Special 


w«»*  v«^4«»#<»,j,^fle; 


490 


Fig.  393. — The  Orgajj  of  Corti'in  the  Guinea  Pig.     (Xakamura.) 

attention,  however,  should  be  directed  to  the  colony  of  modified  cells 
situated  upon  the  basilar  membrane,  the  free  surfaces  of  which 
border  upon  the  endolymph  of  this  tubule.  These  cells  form  the  organ 
of  Corti  which  is  most  directly  concerned  with  the  reception  of  the 
sound  waves  in  the  form  of  vibrations  of  the  lymph  filling  these  scalae. 
The  manner  in  which  this  transfer  is  effected  will  be  more  fully  dis- 
cussed later  on. 

The  Structure  of  the  Organ  of  Corti. — The  basilar  membrane 
forming  the  floor  of  the  central  canal  of  the  cochlea,  gradually  increases 
in  width  from  the  base  to  the  apex  of  the  cochlea.  The  width  of  the 
osseous  lamina,  on  the  other  hand,  decreases  in  a  corresponding 
measure.  Thus,  Henson^  states  that  its  breadth  amounts  to  only 
about  0.041  mm.  below,  but  to  0.495  mm.  above.  Its  total  length 
measures  33.5  mm.  Its  substance  is  formed  by  a  homogeneous  ground- 
substance  containing  numerous  straight  fibers  which  are  suspended 
in  a  radial  manner  between  the  tip  of  the  bony  lamina  and  the  liga- 

1  Archiv  fur  Ohrenheilkunde,  vi,  1873. 


776 


THE    SENSE    OF    HEARING 


mentous  tissue  upon  the  external  wall  of  the  cochlear  canal.     Retzius^ 
has  estimated  the  number  of  these  fibers  at  24,000. 

The  entire  cochlear  canal  is  lined  by  a  single  layer  of  cuboidal 
cells  which  also  extend  across  the  under  surface  of  the  membrane  of 
Reissner.  The  body  of  the  latter  consists  of  an  extremely  thin  layer 
of  connective  tissue  derived  from  the  periosteal  lining  of  the  scala 
vestibuli.^  It  is  to  be  noted  especially  that  the  cells  situated  upon 
the  basilar  membrane,  possess  a  most  peculiar  appearance.  A  single 
cross-section   of   this   particular  area  presents  two  rod-shaped  cells 


Fig.  394, — Diagrammatic  View  of  the  Organ  op  Corti,  the  Sense  Cells,  and  the 
Accessory  STRucTLrREs  of  the  Membranous  Cochlea. 
A,  inner  rods  of  Corti;  B,  outer  rods  of  Corti;  C,  tunnel  of  Corti;  D,  basilar  mem- 
brane; E,  single  row  of  inner  hair  (sense)  cells;  6,  6',  6",  rows  of  outer  hair  (sense)  cells; 
7,  7',  supporting  cells  of  Deiters.  The  ends  of  the  inner  hair  cells  are  seen  projecting 
through  the  openings  of  the  reticulate  membrane.  The  terminal  arborizations  of  the 
cochlea  nerve  fibers  end  around  the  inner  and  outer  hair  cells.      (Testut.) 


which  are  separated  at  their  bases,  but  come  together  above  in  the 
manner  of  the  sides  of  a  roof.  These  cells  are  usually  referred  to  as 
the  inner  and  outer  rods  of  Corti.  The  triangular  space  situated  in 
between  this  double  row  of  inclined  cells,  is  known  as  the  tunnel  of 
Corti.  Internal  to  the  inner  rod  of  Corti  is  a  single  epithelial  cell 
which  sends  a  brush  of  short  and  stiff  projections  into  the  endolymph. 
On  the  outer  side  of  the  outer  rod  of  Corti  are  three  or  four  cells  which 
are  slender  in  shape  and  also  carry  hair-like  processes.^  They  are 
supported  by  the  so-called  cells  of  Deiters.     External  to  these  hair 

^  Das  Gehororgan  der  Wirbeltiere,  ii,  1884. 

2  Stohr,  Anat.  Anzeiger,  1907,  und  Kolmer,  Archiv  fiir  mikr.  Anatomie,  Ixx, 
1907. 

'  Scott,  Jour,  of  Anat.  und  Physiol.,  1909,  also  see:  Nakamura,  tlber  die  Myeli- 
noid-Substanz  in  den  Haarzellen  des  Cortischen  Organes,  Berlin,  1914. 


THE    INTERNAL    EAR    OR    LABYRINTH  777 

cells  are  several  tall  columnar  cells  which  rapidly  decrease  in  height 
until  they  have  attained  the  simple  character  of  the  general  lining 
of  this  tubule.  Practically  the  entire  surface  of  the  organ  of  Corti 
is  covered  by  a  thick  fibrillated  membrane,  the  tectorial  membrane, 
which  takes  its  origin  upon  the  upper  surface  of  the  limbus  and  sweeps 
almost  transversely  througli  tlie  lumen  of  this  canal. 

The  Function  of  the  Organ  of  Corti. — These  different  rows  of  cells 
are  continued  spirally  into  the  tip  of  the  scala  media.  It  has  been 
estimated  that  there  are  more  than  2500  inner  and  13,000  outer  hair 
cells.  Their  total  number  is  generally  given  as  at  least  16,000.  We 
have  every  reason  to  believe  that  these  hair  cells  are  the  elements  which 
receive  the  sound  waves,  this  assumption  being  based  principally 
upon  their  general  appearance  and  position.  In  the  second  place,  it 
is  noted  that  the  cochlear  branch  of  the  auditory  nerve  ascends  through 
the  modiolus  and  directs  its  fibers  radially  through  the  spiral  lamina 
into  the  organ  of  Corti.  Near  the  base  of  the  lamina  these  fibers  tra- 
verse a  ganglion,  known  as  the  ganglion  spirale.  The  cells  of  this 
structure  are  bipolar,  their  peripheral  branches  being  continued  onward 
into  the  basilar  membrane  where  they  lose  their  medullary  sheath 
and  enter  the  epithelium  in  the  region  of  the  inner  hair  cells.  Some 
of  these  fibers  terminate  here,  while  others  continue  onward  and  cross 
the  tunnel  of  Corti  to  enter  the  region  of  the  outer  hair  cells.  In  this 
region  they  terminate  as  fine  filaments  which  invest  the  lower  poles  of 
the  corresponding  cells  of  Deiters. 

The  fact  that  the  rods  of  Corti  are  not  present  in  birds,  which 
doubtlessly  possess  a  very  keen  sense  of  hearing,  shows  that  these 
elements  are  not  essential  to  hearing.  The  same  conclusion  may  be 
drawn  from  the  fact  that  their  number  is  altogether  too  small  to  be 
able  to  receive  the  large  number  of  sound  waves  to  which  we  may  be 
subjected.  Retzius,  for  example,  estimates  their  total  number  at  less 
than  10,000,  of  which  5600  are  inner  rod  cells.  This  exclusion  of  the 
rods  as  direct  factors  in  the  reception  of  the  sound  waves,  leaves  us  free 
to  localize  this  function  in  the  hair  cells.  In  accordance  with  Helm- 
holtz,  it  may  then  be  held  that  the  latter  play  the  part  of  sympathetic 
resonators  which  are  capable  of  reducing  musical  sounds  into  their 
components. 

The  Activation  of  the  Organ  of  Corti. — In  accordance  with  a  sug- 
gestion of  Hensen,  it  has  been  advocated  by  Helmholtz  that  the  constitu- 
ents of  the  organ  of  Corti  are  activated  from  below  by  the  sympa- 
thetic vibrations  of  the  radial  fibers  imbedded  in  the  basilar  membrane. 
It  is  believed  in  this  case  that  the  vibrations  of  the  perilymph  in  the 
scala  tjmipani  are  transmitted  to  these  fibers  and  that  the  latter  in 
turn  stimulate  the  haii'  cells  above  them.  This  contention  harmonizes 
with  the  fact  that  the  basilar  membrane  contains  about  24,000  of 
these  fibers,  and  that  their  length  gradually  increases  from  the  base  to 
the  tip  of  the  cochlea  (135)U  to  234fx).  Thus,  the  fibers  in  the  base 
of  the  cochlea  would  be  adapted  to  high  notes,  and  those  near  the  heli- 


778  THE    SENSE    OF    HEARING 

cotrema  to  deep  notes.  In  accordance  with  this  view,  it  must  be  as- 
sumed that  each  fiber  has  its  own  periodicity  of  vibration  and  is  capable 
of  analyzing  the  simple  waves  of  a  particular  compound  wave.  The 
simultaneous  vibration  of  a  number  of  these  fibers  would  of  course 
give  rise  to  several  sensations  which  are  then  fused  in  consciousness. 
No  definite  statements  can  be  made  at  the  present  time  regarding 
the  manner  in  which  the  vibrations  of  these  fibers  are  transferred  to 
the  hair  cells  and  endings  of  the  auditory  nerve.'' 

Those  physiologists  who  claim  that  these  fibers  are  not  sufficiently 
long  to  serve  as  efficient  resonators,  hold  with  Max  Meyer^  that  (a)  the 
analyzer  is  the  basilar  membrane  itself,  or  (6)  the  vibrations  in  peri- 
lymph are  directly  transferred  to  the  hair  cells  through  the  inter- 
vention of  the  endolymph  of  the  central  scala.  The  first  view  meets 
with  the  same  objections  as  the  resonance  theory  of  Helmholtz.  The 
second,  on  the  other  hand,  has  several  points  in  its  favor,  because  it 
ascribes  a  perfectly  definite  function  to  the  peculiar  hair-like  prolonga- 
tions of  these  cells.  It  is  conceived  that  these  processes  float  free  in 
the  endolymph  of  the  central  canal  and  are,  therefore,  in  the  best  pos- 
sible position  to  receive  the  vibrations  set  up  in  this  fluid  in  conse- 
quence of  the  transferred  oscillations  of  the  lymph  in  the  adjoining 
scala  vestibuli.  These  hairs,  therefore,  serve  the  purpose  of  a  battery 
of  resonators,  capable  of  resolving  the  compound  vibrations  into  their 
simple  constituents.  In  this  case,  the  tectorial  membrane  is  assumed 
to  play  merely  the  part  of  a  dampener  similar  to  the  felt  pad  upon  the 
strings  of  a  piano. 

In  support  of  the  second  view  Ayers^  asserts  that  the  membrana 
tectoria,  as  seen  in  ordinary  preparations,  is  an  artefact  and  is  nothing 
more  than  a  matted  mass  of  hairs  which  in  reality  form  a  waving  plume 
extending  from  the  surfaces  of  the  hair  cells  through  the  endolymph 
to  be  inserted  upon  the  crest  of  the  ridge  immediately  beside  the 
internal  border  of  the  organ  of  Corti.  These  long  extended  processes 
are  activated  by  the  vibrations  in  endolymph  and  transfer  their  im- 
pulses directly  to  the  cells  and  adjoining  nerve  endings. 

To  make  this  list  complete,  it  might  be  mentioned  that  some 
physiologists  believe  that  the  resonating  organ  is  the  tectorial  mem- 
brane itself  which,  however,  vibrates  only  in  segments  and  solely  along 
its  thin  margin.^  Its  vibrations  are  communicated  to  the  hair  cells, 
the  processes  of  which  are  in  this  case  regarded  as  short  stubby  bristles. 

Whichever  theory  we  may  feel  inclined  to  accept,  it  must  be  evident 
that  the  final  analysis  of  the  sound  waves  is  accomplished  in  the  audi- 
tory realm  of  the  cerebi-al  cortex.  Subsequent  to  their  association 
they  are  projected  to  the  place  in  the  medium  from  which  they  appear 

1  Baginsky,  Virchow's  Archiv,  xciv,  1883,  65. 

2  Zeitschr.  fiir  Psyc.  und  Physiol,  der  Sinnesorgane,  xvi,  1898;  also  see:  Ewald, 
Pfliiger's  Archiv,  Ixxvi,  1899,  147,  Yoshii,  ibid.,  1909. 

3  Journal  of  Morphology,  1892. 

*  Ebner,  in  KoUicker's  Handb.  der  Gewebelehre,  iii,  1902,  958. 


THE    INTERNAL    EAR    OR    LABYRINTH  779 

to  have  been  derived.  This  locaHzation,  however,  involves  not  only 
a  judgment  regarding  the  intensity  of  the  sounds  as  individually 
perceived  by  the  two  ears,  but  also  an  analysis  of  the  position  of  the 
head  and  of  the  conjugate  deviation  of  the  eyes.  Naturally,  a  median 
localization  of  the  sound  necessitates  an  equally  intense  activation  of 
the  two  receptors  and  a  lateral  localization,  an  unequal  activation. 
In  the  latter  case,  our  judgments  as  to  right  and  left,  are  surprisingly 
accurate,  although  we  are  frequently  in  error  as  to  whether  the  sound 
has  arisen  in  front  or  behind  us,  above  or  below  us.  Consequently, 
our  ears  act  in  the  manner  of  the  two  eyes  during  binocular  vision, 
our  judgments  regarding  the  special  relationship  of  objects  being 
derived  from  the  two  visual  fields.  It  seems  doubtful,  however,  that 
our  judgments  regarding  the  direction  and  distance  of  sounds  are 
much  less  exact  than  those  pertaining  to  our  visual  impressions.  Thus, 
a  ventriloquist  plays  upon  the  judgment  of  other  persons  by  altering 
the  quality  of  his  vocal  sounds  in  such  a  way  that  they  imitate  the 
peculiarities  of  those  sounds  which  he  desires  to  impart  to  his  hearers. 
He  thus  makes  use  of  perfectly  normal  mental  concepts  of  sounds  to 
produce  an  erroneous  impression. 

Conduction  of  Sound  Waves  by  the  Cranial  Bones. — It  has  been 
pointed  out  that  the  organ  of  Corti  is  activated  by  the  vibrations  in  the 
neighboring  endolymph  and  perilymph,  and  that  the  latter  are  ordi- 
narily the  result  of  the  oscillation  of  the  ossicles  in  consequence  of 
sound  waves.  But,  conditions  may  also  arise  in  space  which  allow  of  a 
direct  transfer  of  these  waves  to  the  bones  of  the  cranium  and  in  turn 
evoke  a  vibration  of  the  lymph  in  the  internal  ear.  Thirdly,  it  is  pos- 
sible to  produce  these  vibrations  by  bringing  a  resonant  body,  such  as  a 
tuning  fork,  in  direct  contact  with  one  of  the  cranial  bones.  If  placed 
upon  the  region  of  the  interparietal  suture,  the  localization  will  be 
median  in  character,  for  the  reason  that  both  ears  are  now  affected  in 
an  equal  measure.  If  one  of  the  ears  is  then  protected  by  placing  the 
tip  of  a  finger  into  the  auditory  meatus,  the  sound  is  immediately 
diverted  into  this  ear,  and,  if  both  ears  are  shielded  in  this  way,  again 
into  the  midline  of  the  cranium.^  In  explaining  this  phenomenon, 
it  must  be  remembered  that  the  oscillations  of  the  lymph  resulting  in 
consequence  of  this  direct  transmission  of  the  sound  waves,  are  also 
transferred  to  the  ossicles  and  to  the  eardrum.  If  the  ear  is  now  held 
shut,  the  initial  energy  of  the  vibration  in  lymph  is  prevented  from 
being  spent  in  this  way,  and  hence,  must  be  able  to  act  with  greater 
intensity  upon  this  particular  receptor.  In  all  these  cases,  however, 
the  projection  is  intracranial,  as  against  the  extracranial  localization 
noted  whenever  the  sound  waves  are  permitted  to  enter  in  the  normal 
way  through  the  auditory  meatus. 

Subjective  sensations  of  sounds,  such  as  ringing  in  the  ears,  most 
commonly  arise  in  consequence  of  a  local  or  general  hypersensitiveness 
of  the  nervous  system.  This  condition  leads  to  spastic  contractions 
1  Weber,  Archiv  fiir  Ohrenheilkunde,  xviii,  1882,  130. 


780  THE    SENSE    OF    HEARING 

of  the  tensor  tympani.  Humming  or  rushing  noises  most  generally 
have  their  origin  in  circulatory  disturbances  (hemic  murmers).  A 
common  entotic  phenomenon  is  the  audibility  of  the  heart  beat  when 
the  left  side  of  the  head  is  placed  upon  a  pillow.  This  position  increases 
the  resonance  of  the  left  internal  ear  in  a  greater  degree  than  that  of 
the  right. 

The  Limits  of  Hearing.  Auditory  Fatigue. — While  inheritance  and 
training  play  an  important  part  in  determining  our  range  of  the  appre- 
ciation of  sounds,  it  is  usually  stated  that  the  human  ear  cannot  be 
activated  by  musical  tones  possessing  a  lesser  vibratory  rate  than  24  to 
30  in  a  second.  Some  persons,  however,  are  capable  of  perceiving 
sounds  of  only  16  vibrations  to  the  second.  Below  this  limit  mere 
sensations  of  pressure  are  produced,  although  some  of  these  low  sounds 
may  give  rise  to  high  overtones  which  are  clearly  recognizable.  The 
upper  limit  of  audibility  of  musical  sounds  is  generally  placed  at 
40,000  double  vibrations  in  a  second.  Beyond  this  point,  the  notes 
give  rise  to  unpleasant  sensations  rather  than  to  true  sounds  and  can- 
not be  used  in  music.  At  about  60,000  they  become  inaudible.  A 
convenient  way  in  which  the  range  of  hearing  may  be  tested  is  to 
strike  steel  rods  of  varying  vibrating  frequency  (Konig). 

It  is  commonly  accepted  that  rhythmically  repeated  or  long  con- 
tinued sounds  eventually  give  rise  to  a  condition  of  auditory  fatigue. 
In  many  cases,  however,  this  fatigue  is  only  apparent  and  is  due  rather 
to  inattention.  Thus,  the  ticking  of  a  watch  may  become  inaudible 
to  us,  because  other  matters  temporarily  occupy  our  attention.  In- 
tense sounds  produce  a  peculiar  deafening  effect,  rather  than  a  true 
fatigue. 

The  Perception  of  Noises. — Noises  form  a  physical  as  well  as  a 
physiological  entity,  because  they  lack  the  rhythmic  and  harmonic 
character  of  musical  sounds.  In  spite  of  this  fact,  however,  they 
possess  a  definite  pitch,  quality  and  intensity.  Helmholtz  has  advo- 
cated the  view  that  they  are  mediated  by  a  special  receptor  formed 
by  the  sensory  epithelium  of  >  the  utricle  and  saccule.  Exner,^  on 
the  other  hand,  states  that  they  are  also  received  by  the  organ  of 
Corti,  and  that  they  activate  a  large  number  of  resonators,  in  contra- 
distinction to  the  musical  sounds  which  affect  only  particular  ones. 
Being  a  believer  in  the  Helmholtz  resonance  theory,  Exner  holds  that 
they  stimulate  the  radial  fibers  of  the  basilar  membrane. 

1  Pfluger's  Archiv,  xiii,  1876,  228. 


SECTION  XXII 
THE  SENSE  OF  EQUILIBRIUM 


CHAPTER  LXV 
THE  SENSE  OF  POSITION.    STATIC  SENSE 

The  Otolithic  Cavity. — This  organ  is  usually  represented  by  a 
membranous  saccule  which  is  placed  in  the  integument  in  free  com- 
munication with  the  outside.  Its  epithelial  Uning  is  beset  with 
long  hair-like  processes,  the  tips  of  which  are  weighted  with  small 
concretions  of  calcium  carbonate,  known  as  otohths.  Many  of 
these  granules  rest  free  among  the  hairs.  The  general  structure  of 
these  otocysts  has  led  physiologists  to  believe 
that  they  are  quite  unable  to  oscillate  in  unison 
with  the  vibrations  in  the  surrounding  medium 
and  cannot,  therefore,  play  a  part  in  the  recep- 
tion of  sounds.  For  this  reason,  it  is  now  com- 
monly held  that  they  are  concerned  with  equili- 
bration and  more  particularly  with  the  percep- 
tion of  position  than  with  that  of  motion;  i.e., 
with  the  "static"  rather  than  with  the  "dyna- 
mic" sense. 

This  conclusion  has  a  definite  experimental 
basis,  because  if  the  otolithic   material  is  re- 
moved, the   animal   shows  disturbances  in  its        -^      00= '  t-      /-. 
position  and  movements.     Thus,  the  destruc-  uthic  Cavity  Showing  the 
tion  of  the   otocyst   in  crustaceans  gives  rise  Lining  Cells  with  their 
to  a  tilting  of  the  head  toward  the  side  on  which  2fJt™  To^r^™""' 
this  injury  has  been  effected.     Quite  similarly, 

if  made  to  move,  this  animal  invariably  moves  about  in  a  circle,  return- 
ing finally  to  the  place  from  which  it  started.  The  same  result  may 
be  obtained  by  cutting  the  nerves  innervating  these  organs.  It 
seems,  therefore,  that  the  otocyst  and  otolith  should  really  be  named 
statocyst  and  statohth  respectively.^  This  nomenclature  seems  to  be 
indicated  the  more,  because  Kreidl,^  has  succeeded  in  varying  the 
equihbration  of  the  crustacean  palemon  by  changing  the  contents  of 
its  statocyst.  At  the  time  of  molting  this  animal  fills  its  statocystic 
cavities  with  granules  of  sand  to  tide  it  over  this  particular  period.     If 

1  Von  Buddenbrock,  Sitzungsber.,  Akad.,  Heidelberg,  1911. 

2  Sitzungsb.,  Akad.  zu  Wien,  cii,  1893,  149. 

781 


782  THE    SENSE    OF    EQUILIBRIUM 

it  was  placed  at  this  time  in  the  vicinity  of  finely  pulverized  iron,  it  used 
this  material  instead  of  the  sand,  with  equally  beneficial  results.  Inas- 
much as  its  otostatic  cavities  are  situated  at  the  base  of  the  antennse 
in  free  communication  with  the  outside,  the  gravity  of  the  iron  could 
be  varied  by  means  of  magnets.  Whenever  this  was  done,  the  animal 
immediately  displayed  pronounced  disturbances  in  its  movements,  lead- 
ing to  a  loss  of  its  proper  position  in  space.  Very  similar  disorders  have 
been  observed  by  Prentiss^  in  the  larvae  of  lobsters  which  had  been  pre- 
vented from  obtaining  a  temporary  substitute  for  their  statohthic  ma- 
terial by  placing  them  in  filtered  sea  water.  Streeter,^  moreover,  has 
shown  that  tadpoles  do  not  acquire  the  power  of  equilibration  until  the 
sixth  day  after  fertihzation,  i.e.,  not  until  the  auditory  vesicles  have 
made  their  appearance.  The  destruction  of  one  of  these  organs  gives 
rise  to  disturbances  in  its  equilibrium  which  may  be  rendered  even  more 
pronounced  by  the  removal  of  both. 

The  Utricle  and  Saccule. — While  we  have  seen  that  the  otoUthic 
cavity  of  the  invertebrates  is  not  an  organ  of  hearing,  it  cannot  be 
denied  that  it  serves  as  the  precursor  of  the  organ  of  hearing  of  the 
higher  vertebrates.  The  auditory  sac,  arising  as  a  depression  in  the 
epiblast  near  the  hindbrain,  becomes  separated  from  the  main  tube, 
but  does  not  enter  into  direct  communication  with  the  outside.  It 
gradually  develops  into  the  variegated  membranous  labyrinth,  consist- 
ing eventually  of  the  central  canal  of  the  cochlea,  the  saccule,  utricle, 
and  the  semicircular  canals.  In  the  lower  vertebrates  the  cochlea 
is  absent,  the  first  indication  if  it  being  presented  by  the  cysticula  of 
the  bony  fish.  Kreidl,^  however,  beheves  that  this  organ  is  still 
too  rudimentary  to  react  to  sounds;  instead,  he  supposes  the  latter  to 
be  received  by  the  cutaneous  sense-organs  in  consequence  of  vibrations 
set  up  in  the  surrounding  water.  It  should  be  noted,  however,  that 
the  fish  are  in  possession  of  a  statohthic  sac  to  which  one  or  more 
semicircular  canals  are  attached.  The  development  of  the  latter 
immediately  suggests  that  these  animals  are  also  equipped  with  a 
dynamic  sense  of  equilibrium. 

Beginning  with  the  terrestrial  animals,  the  cochlea  develops  more 
rapidly,  it  being  present  in  an  elementary  form  in  the  amphibia  and 
reptiha  and  in  its  more  complete  spiral  form  in  birds.  In  the  latter, 
the  central  canal  of  the  cochlea  is  united  with  the  saccule  as  well  as  with 
the  other  endolymphatic  spaces.  The  labyrinth  attains  a  structure 
comparable  to  that  of  man,  only  in  the  higher  mammals.  Situated 
directly  within  the  osseous  vestibule,  we  have  two  vesicular  enlarge- 
ments, namely,  the  saccule  and  utricle.  The  former  attains  a  length 
of  about  3  mm.  and  a  width  of  2  mm.  It  is  placed  very  close  to  the 
orifice  of  the  scala  vestibuli  of  the  cochlea.     In  the  direction  of  the 

^  Bull.  Mus.  of  Comp.  Zoology,  Harvard  Univ.,  xxxvi,  1901. 

2  Jour,  of  Exp.  Zoology,  iii,  1906,  543. 

3  Pfluger's  Archiv,  Ixiii,  1896,  581.  The  contrary  view  is  held  by  Zenneck, 
Pfltiger's   Archiv,   xcv,    1903,    346. 


THE    SENSE    OF    POSITION.       STATIC    SENSE 


783 


latter  it  tapers  into  a  narrow  duct,  measuring  1  mm. 
in  length  and  0.5  mm.  in  height.  It  finallj^  connects 
with  the  central  canal  of  the  cochlea  a  short  distance 
above  its  expanded  lower  extremity.  The  other 
pole  of  the  saccule  communicates  with  the  utricle 
by  means  of  the  ductus  endolymphaticus.  The 
utricle  is  irregular  in  shape  and  measures  6-7  mm. 
in  length  and  5  mm.  in  breadth.  It  gives  origin  to 
the  semicircular  canals.  Of  particular  importance 
to  us  at  this  time  is  the  so-called  recessus  utriculi, 
a  blind  forward  projection  from  the  main  cavity 
which  contains  the  macula  acustica.  This  area  is 
formed  by  auditory  epithelium  which  is  beset  with 
hair-like  processes  carrying  otolithic  crystals,  and  is 
innervated  by  fibers  from  the  auditory  nerve.  A 
similar  patch  of  sensory  epithelium  is  contained  in  the 
saccule. 

Three  views  have  been  held  regarding  the  func- 
tion of  the  macula  utriculi  and  macula  sacculi, 
namely  (a)  that  they  are  the  recipients  of  the  sound 
waves,  (6)  that  they  mediate  irregular  vibrations  or 
noises,  and  (c)  that  they  serve  the  purpose  of  stato- 
lithic  organs.  The  first  contention  may  be  dis- 
carded, because  it  has  now  been  thoroughly  estab- 
lished that  the  cochlea  is  fully  capable  of  taking  care 
of  this  function.  The  second  view  is  based  merely 
upon  assumptions  and  need  not  be  discussed  further. 
By  exclusion,  therefore,  this  discussion  may  be  re- 
stricted to  the  view  of  Brener,^  which  holds  that 
these  structures  inform  us  regarding  the  position  of 
the  head  when  at  rest  or  when  the  entire  body  is  en- 
gaged in  making  progressive  movements  in  one  direc- 
tion or  another.  It  is  conceived  that  the  otolithic, 
or  rather,  statoHthic  crystals  evoke  stimulations  by 
means  of  their  weight  resting  upon  the  neighboring 
hair-like  processes.  This  weight,  of  course,  is  not 
objective,  but  is  lessened  somewhat  bj^  the  fact  that 
it  is  exerted  in  a  medium  of  endolymph.  At  any 
time  when  the  head  is  tilted,  their  lines  of  gravity 


\ 


._r 


i\ 


Fig.  396. — Nerve-endings  upon  the  Intrafusal  Muscle-fibers  of  a  Axuscle-spintile 
OF  the  Rabbit.     Moder.\tely  Magnified.     Methylene-blue  Prep.^ration.     (Dogiel.) 

a,  Large  medullated  fiber  coming  off  from  'spindle'  nerve  and  passing  to  end  in  an 
annulo-spiral  termination  on  and  between  the  intrafusal  fibers;  b,  fine  medullated 
fiber  coming  off  from  the  same  stem  and  dividing.  Its  branches,  c,  pass  towards  the 
ends  of  the  muscle-fibers  and  terminate  in  a  number  of  small  localized  arborizations,  like 
end-plates. 

1  Pfltiger's  Archiv,  Ixviii,  1897,  596. 


784 


THE    SENSE    OF    EQUILIBRIUM 


are  shifted,  so  that  the  different  hairs  are  mechanically  acted  upon 
with  varying  force.  Furthermore,  it  should  be  noted  that  the  maculae 
acusticse  occupy  different  planes  in  space  so  that  they  are  affected 
differently  by  one  and  the  same  position,  or  progressive  movement. 
These  statolithic  receptors  supplement  the  function  of  the  receptors 
in  the  ampullae  of  the  semicircular  canals  which,  as  will  be  shown  later, 
mediate  the  sensations  of  rotatory  motion  and  are,  therefore,  primarily 
concerned  with  the  production  of  the  dynamic  sense.  In  both  cases, 
these  sensations  give  rise  to  reflexes  which  are  essential  for  the  main- 
tenance of  the  equilibrium.  Obviously,  these  reflexes  initiate  first 
of  all  certain  muscular  movements,  which  are  executed  in  compensa- 
tion for  these  static  and  dynamic  sensations.  In  last  analysis,  how- 
ever, the  static  and  dynamic  senses  are  compound  in  their  nature, 
because  they  depend  not  only  upon  the  sensations  derived  from  the 
corresponding  sensory  structures  of  the  labyrinth,  but  also  upon  those 


Fig.  397. — Organ  of  Golgi  from  Hlhvian  Tendo  Achillis.     C'hlorid  of  Gold  Prepa- 
ration.     (Ciaccio.) 
m,  Muscular  fibres ;  t,  tendon-bundles;  g,  Golgi's  organ;  n,  two  nerve-fibres  passing 
to  it. 


obtained  from  the  retinae,  from  the  cutaneous  receptors,  and,  as  will 
be  shown  later  on,  from  the  deep  receptors  situated  in  the  muscles, 
joints  and  tendons. 

It  is  also  to  be  noted  that  these  organs  of  equilibrium  are  thoroughly 
protected  against  all  direct  influences  from  without,  i.e.,  their  activa- 
tion can  only  be  effected  by  changes  arising  within  the  animal  itself. 
For  this  reason,  the  static  and  dynamic  sense-organs  are  commonly 
regarded  as  belonging  to  the  proprioceptive  system  of  receptors. 
Furthermore,  since  the  static  and  dynamic  senses  are  really  compound 
senses,  because  amphfied  and  perfected  by  sensations  received  from 
other  sense-organs,  such  as  the  retinae  and  the  cutaneous  corpuscles, 
their  development  actually  necessitates  a  harmonious  interaction 
between  different  exteroceptors  and  proprioceptors. 

The  Muscle  Spindles. — It  is  a  well-known  fact  that  the  muscles 
and  tendons  as  well  as  the  lining  of  the  joints  and  the  deep  skin  are 


THE    SENSE    OF    MOVEMENT.       DYNAMIC    SENSE  785 

supplied  witli  a  tyi)e  of  scrisc-orfran,  Mu;  exclusive  function  of  which 
appears  to  Ix^  to  giv(>  infoi-iuation  regard inj;  the  position  of  our  limbs 
and  body  as  a  whole.  The  one  contained  in  muscle-tissue,  is  formed 
by  one  or  more  muscle  fibers  which  are  permeated  by  lymph-spaces 
and  are  enveloped  in  a  sheath  which  is  made  up  of  several  layers  of 
fibrous  tissue.  The  nerve  fiber  entering  this  structure,  winds  spirally 
around  these  fibers  and  eventunll}^  terminates  in  small  platelets  upon 
their  surfaces.  In  tendinous  tissue  this  sense-organ  appears  as  an 
arborization  of  dehcate  nerve-filaments  upon  the  surfaces  of  the  in- 
dividual strands  of  tissue.  This  arrangement  enables  the  fibers  of 
the  muscle  to  exert  a  certain  pressure  upon  these  nerve-endings,  and  to 
produce  impulses  which  experience  has  taught  us  to  interpret  in  terms 
of  a  definite  degree  of  contraction  of  the  muscle  or  of  the  position 
of  the  part  moved  by  it.  This  central  association  which,  as  we  have 
seen,  is  effected  by  the  cerebellum,  constitutes  the  muscle-sense. 
These  sensations,  however,  do  not  amplify  merely  the  sense  of  position, 
but  also  that  of  motion,  because  the  muscles  undergo  constant  changes. 


CHAPTER  LXVI 
THE  SENSE  OF  MOVEMENT— DYNAMIC  SENSE 

The  Semicircular  Canals. — The  membranous  semicircular  canal 
occupies  from  one-third  to  one-fifth  of  the  entire  lumen  of  the  osseous 
canal.  The  space  intervening  between  its  outer  wall  and  the  inner 
surface  of  the  bony  canal,  is  filled  with  perilymph  and  the  suspensory 
bands  which  hold  the  membranous  tube  in  place  (Fig.  388).  In  cross- 
section  the  latter  presents  an  oval  or  elUptical  outline,  and  is  expanded 
into  a  cavernous  space  very  shortly  after  it  leaves  the  utricle.  At  this 
particular  point  it  possesses  a  diameter  about  twice  as  long  as  that 
of  its  remaining  portion.  This  enlargement  which  is  known  as  the 
ampulla,  occupies  very  nearly  the  entire  lumen  of  the  osseous  canal 
and  lies  in  close  contact  with  the  wall  of  the  latter  at  the  convexity 
of  the  semicircle.  It  gives  lodgment  to  the  sensory  epithelium  mediat- 
ing dynamic  sensations.  The  latter  are  conveyed  fom  here  to  the 
center  by  the  vestibular  branch  of  the  auditory  nerve.  ^ 

In  cross-section  each  ampulla  presents  a  transverse  prominence 
which  is  known  as  the  crista  acustica.  This  ridge  projects  far  into  the 
lumen  of  this  passage  and  is  beset  with  the  sensory  epithelium.  The 
latter  diflPers  from  the  flat  lining  of  the  remaining  portion  of  the  semi- 
circular canal  in  that  it  consists  of  elongated  columnar  cells  which  are 

1  Ewald,  Physiol.  Untersuchungen  iiber  das  Endorgan  des  Nerv.  Octavus, 
Wiesbaden,  1892. 

50 


786 


THE    SENSE    OF   EQUILIBRIUM 


surmounted  by  long  tapering  processes.  These  hair-like  extensions 
measure  about  0.03  mm.  in  length  and  project  straight  into  the  en- 
dolymph.  Somewhat  above  the  basement  membrane  these  cells  termi- 
nate in  a  rounded  extremity  which  lies  in  relation  with  the  finely 


Fig.  398. — Diagrammatic  Representation  of  the  Structure  of  the  Ampulla  of  a 

Fish. 
The  columnar  cells  of  the  crista  acustica  (c)  are  beset  with  hair-like  prolongations 
which  float  free  in  the  endolymph.     A'',  nerve  fibers  leading  away  from  ampulla. 

subdivided  axis  cylinders  of  the  vestibular  nerve  fibers.  The  space 
between  the  lower  poles  of  these  hair-cells  and  the  basement  mem- 
brane is  taken  up  by  the  fiber  cells  of  Retzius^  which  present  themselves 
as  long  filaments  showing  at  one  point  a  nuclear  enlargement. 

The  Relative  Position  of  the  Semi- 
circular Canals.  2 — The  three  osseous 
semicircular  canals  take  their  origin 
from  the  vestibular  enlargement  of  the 
labyrinth,  while  the  three  membranous 
canals  arise  from  the  utricle.  Since  two 
of  these  tubes,  namely,  the  two  vertical 
ones,  become  confluent  before  they 
again  return  to  this  space,  they  possess 
only  five  orifices  in  all.  The  three 
canals  of  each  side  are  arranged  in  such 
a  way  that  they  cover  three  distinct 
planes  which  lie  approximately  at  right 
angles  to  one  another.  The  external 
or  horizontal  canal  measures  15  mm.  in 
length  and  traverses  a  plane  at  right 
angles  to  the  mesial  plane  of  the  body 
Fig.  399.-FIGURE  Showing  the   (Fig-  399^).     It  occupies,  therefore,  a 

Position  of  the  Three  Semicircular  horizontal  position  when  the  head  is  held 
Canals  in  the  Skull  of  the  Pigeon.    ^^.^^^^     j^g  ampulla  is  located  anteriorly. 

The  anterior  or  superior  canal  is  placed 
nearly  vertical  at  an  angle  of  45°  to  the  mesial  plane  of  the  body  (A). 

1  Biolog.    Untersuchungen,    vi;    also:  Brener,   Sitzungsber.,   Akad.   zu   Wien, 
cxii,  1903. 

2  First  called  attention  to  by  Cyon  (1873),  Brown  (1874),  and  Mach  (1875). 


THE    SENSE    OF   MOVEMENT — DYNAMIC    SENSE 


787 


Fig.  400. — Diagram  to 
Show  the  Position  of  the 
Semicircular  Canals  To- 
ward One  Another. 


It  is  19  mm.  in  loii{:;11i  and  rises  to  a  lii^hor  level  than  any  other  part  of 
the  labyrinth,  its  location  heinji;  indieated  upon  the  upper  surface  of  the 
petrous  portion  of  the  temporal  bone  by  an  arched  prominence.  Its 
ampulla  is  situated  in  front.  The  posterior  or  inferior  canal  (P)  is  also 
placed  nearly  vertical  at  an  angle  of  45°  to  the  mesial  plane  of  the  body 
but  in  such  a  way  that  it  inclines  toward  the  superior  canal  at  a  right 
angle.  It  measures  22  mm.  in  length  and  its 
ampulla  lies  at  the  back  part  of  the  vestibule. 
A  comparison  of  the  planes  of  these  canals 
with  those  of  the  canals  on  the  opposite  side 
shows  immediate^  that  the  left  anterior  covers 
the  same  plane  as  the  right  posterior,  and  the 
right  anterior  that  of  the  left  posterior.  It  is 
evident,  therefore,  that  they  supplement  one 
another.  In  this  connection,  attention  should 
also  be  called  to  the  fact  that  the  vestibular 
division  of  the  auditory  nerve  divides  into  two 
branches,  namely,  into  the  ramus  utriculo-ampullaris  and  the  ramus 
sacculo-ampullaris.  The  former  innervates  the  utricle  and  ampullae 
of  the  superior  and  horizontal  canals,  and  the  latter,  the  saccule  and 
ampulla  of  the  posterior  canal. 

The  Effects  of  Lesions  of  the  Semicircular  Canals. — The   first 
accurate  investigations  pertaining  to  the  function  of  the  semicircular 

canals,  have  been  made  by  Flourens^ 
upon  pigeons,  these  animals  having 
been  selected  for  this  purpose  because 
their  labyrinth  is  more  accessible  to 
operative  procedures  than  that  of 
the  mammals.  It  was  found  first  of 
all  that  the  destruction  of  the  vesti- 
bule and  adjoining  semicircular  canals 
does  not  impair  the  sense  of  hearing, 
but  merely  evokes  disorders  of  equili- 
bration, which,  in  accordance  with 
Goltz,2  are  the  result  of  an  abolition 
of  function  and  not  of  a  loss  of  stimu- 
lation. Thus,  it  could  easily  be  shown 
that  the  unilateral  destruction  of  the 
canals  renders  the  animal  unable  to 
maintain  its  position.  If  it  is  made  to 
move,  it  sways  and  repeatedly  tumbles 
The  head  remains  tilted  toward  the 
operated  side  and  is  even  held  in  an  inverted  position.  These  symp- 
toms disappear  in  the  course  of  three  or  four  weeks  so  that  the  animal 

1  Compt.  rend.,  lii,  1828;  also :  Vulpian,  Lemons,  sur  la  physiol.  du  syst.  nerveux, 
Paris,  1866. 

2  Pfluger's  Archiv,  iii,  1870,  172. 


FiQ.  401. — Abnormal  Posture  of 
Pigeon,  in  Which  the  Labyrinth  had 
BEEN  Extirpated  on  One  Side  Five 
Days  Previously.     (Ewald.) 

toward  the  side  of  the  injury. 


788  '  THE    SENSE    OF    EQUILIBRIUM 

is  again  able  to  fly  and  to  walk,  althoup,h  it  continues  to  suffer  from  a 
certain  loss  of  tonus  of  its  muscles,  principally  of  those  of  the  head  and 
trunk  on  the  side  opposite  to  the  injury. 

The  destruction  of  the  canals  on  the  two  sides  gives  rise  at  first  to 
a  complete  loss  of  equilibrium,  so  that  the  animal  can  neither  walk  nor 
fly  unless  supported.  It  tends  to  assume  a  quiet  attitude,  but  when 
made  to  move,  executes  violent  forced  and  incoherent  movements 
which  may  even  cause  its  destruction.  Its  muscles  are  abnormally 
flaccid  and  the  joints  unusually  Imiber.  So  small  a  weight  as  20 
grams  attached  to  its  bill  or  neck,  suffices  to  keep  the  head  perma- 
nently in  the  most  abnormal  position,  and  to  make  it  sway  in  the  direc- 
tion of  the  weight.  These  disorders  gradually  disappear  in  the  course 
of  a  few  weeks.  The  animal  learns  to  walk  again  by  making  use  of  the 
sensations  of  sight  and  touch.  The  muscular  weakness,  however, 
persists  and  losses  of  equilibrium  may  be  brought  about  at  any  time 
later  on  by  bandaging  the  eyes. 

These  defects  may  be  localized  and  restricted  to  single  planes  of  the 
body  by  destroying  only  one  of  these  canals.  Thus,  the  loss  of,  say 
the  horizontal  canal,  invariably  causes  the  pigeon  to  make  forced 
movements  of  the  head  in  the  horizontal  direction,  but  any  unusual 
excitation  immediately  leads  to  more  general  rotary  movements  of  the 
entire  body.  The  length  of  time  during  which  these  symptoms  remain 
in  evidence,  depends  upon  the  location  and  extent  of  the  lesion;  at 
all  events,  it  does  not  suffice  to  destroy  solely  the  bony  canal  or  to  let 
the  perilymph  escape  through  a  fistulous  opening.  These  defects  are 
quickly  compensated  for,  provided  the  membranous  canal  is  left  intact. 
Decided  symptoms  can  only  be  produced  by  opening  the  latter  widely 
and  as  close  to  the  ampulla  as  possible. 

The  destruction  of  the  labyrinth  in  amphibia  is  followed  by  symp- 
toms which  are  very  similar  to  those  just  enumerated.  Thus,  its 
removal  on  one  side  causes  the  animal  to  tilt  its  head  and  to  move 
about  in  a  circle  toward  the  injured  side.  Moreover,  when  this  animal 
is  placed  upon  its  back,  it  experiences  great  difficulty  in  righting  itself, 
and  when  made  to  swim,  frequently  executes  rotary  movements 
toward  the  operated  side.  Its  musculature  exhibits  a  decided  loss  of 
tonus  and  precision  of  action.  Disorders  of  a  very  similar  kind  are 
exhibited  by  mammals  after  the  destruction  of  one  or  more  sets  of 
semicu'cular  canals. 

The  Effects  of  Stimulation  of  the  Semicircular  Canals. — Ewald^ 
has  succeeded  in  rendering  certain  canals  functionally  useless  by 
opening  their  bony  wall  with  a  dentist's  burr  and  temporarily  com- 
pressing their  membranous  tube  by  means  of  a  plug  of  amalgam,  but 
the  disorders  in  the  plane  of  this  particular  canal  were  evinced  only 
after  the  corresponding  membranous  tube  on  the  opposite  had  also 

1  Physiol.  Untersuchungen  iiber  das  Endorgan  des  Nervus  octavus,  Wiesbaden, 
1892;  also:  Schrader,  Pfliiger's  Archiv,  xli,  1893,  75. 


THE    SENSE    OF   MOVEMENT — DYNAMIC   SENSE  789 

been  blocked.  Konip;  and  Brcner'  have  obtained  very  similar  results 
by  painting  the  ampulla  with  cocain  so  as  to  paralyze  the  nerve- 
end  inp;s.  These  data  serve  to  contradict  the  view  sometimes  advocated, 
that  the  disorders  following;  lesions  of  the  semicircular  canals,  are  phe- 
nomena of  stimulation  rather  than  of  abolition  of  functioii  (Ausfalls- 
erscheinungen).  Besides,  of  course,  we  are  in  possession  of  the  fact 
that  these  disorders  are  generally  lasting  in  character. ^  Ewald  has 
also  stimulated  the  membranous  canal  by  pressing  upon  it  with  a 
bristle  inserted  thrc.ugh  an  opening  in  the  bony  canal,  and  by  blowing 
a  current  of  air  upon  it  through  a  narrow  tube.  In  another  set  of 
experiments  the  endolymph  was  made  to  circulate  by  this  means  first 
in  one  direction  and  then  in  the  other.  In  the  dog-fish,  Lee^  has  found 
that  pressure  upon  any  particular  ampulla  gives  rise  to  movements 
of  those  fins  which  this  animal  ordinarily  employs  in  moving  in  the 
plane  of  the  canal  stimulated.  Electrical  stimulation  of  the  canals 
has  been  resorted  to  by  Brener.  It  gives  rise  to  the  so-called  galvano- 
tropic  reaction,  consisting  in  a  deviation  of  the  head  toward  the  anode. 
All  these  procedures  have  fully  confirmed  the  theory  of  Brener  and 
Mach  which  holds  that  the  specific  stimulant  of  the  sensory  epithelium 
of  the  ampulla  is  the  movement  of  the  endolymph.  Besides,  it  has 
been  made  evident  that  these  canals  evoke  movements  only  along  par- 
ticular planes  of  the  ])ody. 

Labyrinthine  Reflexes  and  Tonus. — The  sensations  of  movement 
with  which  we  are  concerned  at  the  present  time  are,  of  course,  passive 
in  their  nature  and  enable  us  to  form  judgments  regarding  movements 
along  straight  and  curved  lines.  These  purely  labyrinthine  impres- 
sions, however,  are  supplemented  by  others  received  from  the  retinae, 
the  cutaneous  receptors,  and  the  proprioceptors  proper.  It  cannot 
surprise  us,  therefore,  to  find  that  this  relationship  is  sometimes  re- 
versed, so  that  the  labyrinthine  sensations  become  associated  with 
compensatory  reactions  of  different  kinds.  Chief  among  these  are 
movements  of  the  eyes  and  head.  If  a  frog  is  placed  upon  a  board  and 
is  slightly  moved  around  its  transverse  axis,  it  raises  and  lowers  its 
head  against  the  direction  of  this  movement.  In  a  similar  way,  if 
rotated  upon  a  horizontal  disc,  it  bends  its  body  against  the  direction 
of  the  rotation.  These  compensatory  reactions  cease  immediately 
if  the  labyrinth  is  destroyed  or  if  the  nerve  fibers  leading  from  it  are 
cut.  Equally  pronounced  effects  may  be  obtained  in  the  fish,*  birds 
and  mammals.  Since  these  compensatory  movements  may  also  be 
evoked  in  the  blind  and  are,  therefore,  entirely  independent  of  visual 
sensations,  their  labyrinthine  origin  cannot  be  doubted. 

As  has  been  pointed  out  by  Purkinje,   Ewald  and  Stein,^  any 

1  Sitzungsber.,  Akad.  zu  Wien,  cxii,  1887,  1903. 

2  Gaglio,  Archiv  ital.  de  biologie,  xxxi,  1899,  377. 

3  Jour,  of  Physiol.,  xvii,  1895,  192. 
*Loeb,  Pfluger's  Archiv,  xlix,  1891,  175. 
6  Zentralbl.  fur  Physiol.,  xiv,  1900,  222. 


,790  THE    SENSE    OF    EQUILIBRIUM 

unusual  rotation,  say,  around  the  longitudinal  axis  of  the  body,  gives 
rise  to  a  horizontal  nystagmus  of  the  eyes.  This  phenomenon  con- 
sists in  a  slow  latei'al  movement  of  the  eyes  in  the  plane  of  the  rotation 
which,  however,  is  soon  stopped  and  superseded  by  an  abrupt  return 
of  the  eyes  into  the  midline.  This  rotation-nystagmus  is  to  be  sharply 
differentiated  from  that  form  of  nystagmus  which  is  frequently 
exhibited  by  persons  looking  out  of  the  window  of  a  railway  car.  The 
former  occurs  even  in  the  dark  and  in  blind  persons,  while  the  latter 
does  not,  and  may  be  suppressed  by  fixedly  gazing  into  space.  A 
nystagmus  of  the  entire  head  is  often  observed  in  birds  when  made  to 
stand  upon  a  rotating  surface.  The  head  is  at  first  turned  against  the 
direction  of  the  rotation  and  is  then  made  to  execute  jerky  move- 
ments around  the  long  axis  of  the  body. 

Compensatory  movements  of  the  entire  body  are  frequently 
noticed  after  rather  excessive  rotation.  Thus,  if  we  turn  around  the 
longitudinal  axis  of  our  body  a  number  of  times  and  then  suddenly 
stop,  it  will  be  found  that  the  objects  in  space  continue  to  move  against 
the  direction  of  the  rotation,  while  we  ourselves  leave  our  previous 
position  and  sway  toward  the  rotation.  It  is  to  be  noted,  how- 
ever, that  this  compensation  is  forced  upon  us  reflexly  and  should  not 
be  mistaken  for  the  ordinary  effects  of  the  momentum  of  the  I'otation. 
In  addition,  it  is  easily  observed  that  these  compensatory  movements 
are  confined  chiefly  to  the  head  and  trunk  and  would,  in  the  absence 
of  corresponding  movements  of  the  legs  and  arms,  give  rise  to  a  com- 
plete loss  of  equilibrium. 

These  rotation  experiments  should  be  executed  with  some  caution, 
because  in  hypersensitive  persons  they  are  prone  to  produce  nausea, 
vomiting,  muscular  weakness,  disturbances  in  vision  and  slight 
cardio-inhibitory  effects.  For  this  reason,  it  is  commonly  held  that 
seasickness  is  caused  by  an  unusual  and  excessive  stimulation  of  the 
static  and  dynamic  sense-organs.  A  similar  complex  of  symptoms, 
aggravated,  however,  by  vertigo,  forced  movements  and  a  constant 
ringing  in  the  ears,  is  presented  by  Meniere's  disease, '^  The  latter 
seems  to  have  its  origin  in  an  inflammatory  and  hemorrhagic  affec- 
tion of  the  semicircular  canals  and  neighboring  nerve  fibers.  It  is 
also  well  recognized  that  the  injection  of  solutions  into  the  tympanic 
cavity  as  a  curative  means  in  affections  of  the  middle  ear  may  give 
rise  to  vertigo  and  nystagmus;  in  fact,  in  some  persons,  loud  noises 
suffice  to  induce  these  symptoms. 

The  character  of  the  results  obtained  with  deaf  persons,  differs  with 
the  extent  of  the  lesion.  Inasmuch  as  only  about  65  per  cent,  of  these 
persons  show  a  lesion  of  the  canals  in  addition  to  that  of  the  cochlea, 
it  cannot  surprise  us  to  find  that  many  of  them  present  absolutely 
no  disorders  of  their  senses  of  position  and  movement.  The  others 
have  learned  in  the  course  of  time  to  compensate  for  the  disturbances 

1  Gaz.  m^d.  de  Paris,  1861;  also:  Frankl-Hochwart,  Das  Menier6sche  Sympto- 
men-complex,  Wien,  1906. 


THE    SENSE    OF   MOVEMENT DYNAMIC    SENSE  791 

in  these  sensations  and  behave  normally  unless  subjected  to  unusual 
conditions.  Thus,  tlie  tests  of  James'  have  proved  180  among  500 
deaf  persons  to  be  without  vertigo  when  rotatcul,  and  15  among  25 
deaf  persons  to  lose  tlieir  senses  of  orientation  while  diving.  Normal 
persons,  of  course,  behaves  very  dilfcMinil ly;  19*.)  of  th(!  '200  (examined 
displayecl  vertigo  and  forced  movements. 

The  general  weakness  of  the  musculature  following  injuries  to 
the  labyrinth,  is  attributed  by  Ewald  to  a  loss  of  the  labyrinthine 
tonus,  mediated  by  a  set  of  impulses  which  reflexly  keep  the  mus- 
culature in  a  state  of  alertness.  This  effect  is  obtained  through  the 
intervention  of  the  cerebellum  with  which  the  labyrinth  is  in  close 
functional  relation.  Thus,  we  find  that  the  vestibular  fibers  of  the 
auditory  nerve  terminate  in  the  nucleus  of  Deiters  and  the  nucleus 
of  Bechterew,  where  reflex  connections  are  formed  with  the  cranial 
nerves  and  the  different  motor  centers.  Connections  are  also  estab- 
lished here  with  the  nucleus  fastigius  and  the  cortex  of  cerebellum. 
The  semicircular  canals,  therefore,  serve  as  a  sense-organ  of  the 
cerebellum,  this  central  structure  enabling  the  sensations  derived 
from  them,  to  influence  the  tonus  and  behavior  of  the  musculature 
and  hence,  also  muscular  coordination  and  the  equilibrium. 

The  Activation  of  the  Hair-cells  of  the  Ampulla. — The  first  definite 
explanation  of  the  action  of  this  receptor  has  been  given  by  Goltz^ 
who  assumed  that  the  endolymph  of  these  canals  rests  upon  the 
sensory  epithelium  with  a  certain  pressure  and  that  this  pressure 
changes  with  the  position  of  the  head.  But,  while  he  regards  them 
very  distinctly  as  organs  of  equilibration,  he  seems  to  believe  that 
they  are  activated  solely  by  hydrostatic  differences.  This  principle 
has  been  more  fully  developed  by  Brener,^  but  this  investigator 
abandons  the  hydrostatic  factor  or  gravitation  almost  altogether 
and  puts  in  its  place  a  hydrodynamic  mechanism.  This  amphfied 
theory  which  has  been  materially  strengthened  by  a  number  of  observa- 
tions made  by  Mach  and  Brown,^  brings  forth  the  conception  that  the 
hair-cells  constitute  the  peripheral  elements  of  equihbrium,  and  that 
their  activation  is  accomplished  by  the  changes  in  the  pressure  which 
the  endolymph  must  suffer  whenever  the  canals  are  moved.  Thus,  it  is 
assumed  that  the  different  movements  of  the  head  give  rise  to  oscil- 
lations of  the  endolymph  which  in  turn  affect  the  position  of  the  hair- 
like  processes  of  the  ampullar  lining  cells.  To  be  sure,  the  simple 
effects  of  gravity  cannot  be  excluded  altogether,  but  this  theory 
subordinates  the  latter  completely  to  those  of  movement. 

If  a  tumbler  is  filled  with  water  and  is  twirled  upon  a  rotating  disc, 
it  will  be  noted  that  its  walls  move  first,  while  the  water  lags  behind, 
and  exerts  a  pressure  in  the  opposite  direction.     If  the  twirling  is 

^Amer.  Jour,  of  Otology,  1887;  also:  Kreidl,  Pfluger's  Archiv,  li,  1892,  119. 

2  Pfluger's  Archiv,  xxx,  1870,  172. 

^  Sitzungsb.  der  Akad.  zu  Wien,  cxii,  1903. 

*  Jour,  of  Anat.  and  Physiol.,  viii,  1874,  327. 


792 


THE    SENSE    OF    EQUILIBRIUM 


continued  for  a  brief  period  of  time,  a  point  will  be  reached  when  the 
walls  and  the  water  move  with  practically  the  same  velocity.     Im- 


FiG.  402. — DiAGR.\irxL\Tic  Represextatiox  of  a  Model  Illustr-^testg  the  Devl^tiox 
OF  THE  Hair  Processes  of  the  Ampulla. 
D,  disc  rotated  by  hand;  T,  circular  glass  tube  filled  with  water;  B,  bulbular  enlarge- 
ment containing  a  long  camel's  hair  brush,  vertically  placed. 

mediately  upon  ceasing  the  rotation,  the  walls  are  brought  to  a  stand- 
still, while  the  water  continues  to  move  in  this  direction  until  it  is 

finall}^  stopped  by  the  friction.  These 
phenomena  may  be  illustrated  in  a  more 
striking  manner  with  the  help  of  a  cir- 
cular glass  tube  filled  with  water  and 
enlarged  at  one  point  for  the  reception 
of  a  bundle  of  soft  hairs  placed  trans- 
versely into  its  lumen  (Fig.  402).  "\Mien 
rotated,  this  primary  and  secondary 
dissociation  between  the  movements  of 
the  walls  of  the  tube  and  the  water  are 
now  made  more  evident  by  the  devia- 
tion of  the  hairs,  first  against  and  then 
in  the  direction  of  the  rotation. 

If    this   hydrodynamical    principle 
is   appHed  to  the  semicircular  canals. 
Fig.   403.— Diagram  Illustrat-  it  must  be  concluded  that  the  move- 
iNG  THE  Position-  of  the  Hair  Pro-  ment  of  the  head  gives  rise  to  a  move- 

cesses  of  the  Ampulla  on  Rotation 
of  the  Canal. 

A,  the  canal  being  moved  in  the 
direction  of  the  black  arrow,  the  en- 


ment    of   the    canals   situated   in   this 
particular  plane.     To  begin  with,  the 
endolymph   lags   behind    the  walls  of 
doiymph  at  first  lags  behind.    The  ^he  canals,  but  soon  attains  the  same 

hairs  processes  are  deviated  against  ,  . ,        i    ^  ,  t       .1 

speed  as  the  latter.  Lastly,  it  con- 
tinues in  this  direction  even  after  the 
canals  have  ceased  to  move  until  its 
motion  has  again  been  arrested.  This 
implies  that  the  hair  processes  are  first 
turned  against  the  rotation,  then  vertically  into  the  fluid,  and  lastly 


the  rotation  from  a  to  h.  On  stop- 
ping the  rotation  of  the  canal,  the 
endolymph  is  carried  onward  in  the 
direction  of  the  red  arrow  deviating 
the  hair  processes  from  a  to  c. 


THE    SENSE    OF   MOVEMENT — DYNAMIC    SENSE  793 

in  the  direction  of  the  rotation.  These  progressive  deviations  of  the 
hairs  evoke  those  sensations  which  inform  us  regarding  the  direction 
and  extent  of  the  movement  executed  by  us.  It  should  })e  emphasized, 
however,  that  the  endolymph  does  not  move  about  in  a  circle  through 
the  entire  canal,  but  undergoes  simply  the  slightest  possible  oscilla- 
tions in  the  manner  just  indicated  with  the  help  of  the  preceding 
schema.  This  must  necessarily  be  so,  because  (a)  the  internal  diameter 
of  the  semicircular  canals  of  man  measures  only  0.1  mm.  (0.04  mm.  in 
the  pigeon),  (6)  because  txicir  course  is  not  absolutely  circular,  and 
(c)  because  the  endolymph  possesses  a  relatively  high  viscosity. 

Naturally,  only  those  hair  cells  can  be  affected  by  a  certain  gen- 
eral movement  which  lie  in  this  particular  plane.  It  has  previously 
been  mentioned  that  the  semicircular  canals  act  in  pairs,  i.e.,  the 
anterior  of  one  side  is  stimulated  simultaneously  with  the  posterior 
of  the  opposite  side.  Both  together  control  movements  along  vertical 
planes.  The  horizontal  canals  also  act  in  unison,  but  are  chiefly 
concerned  with  movements  along  the  horizontal  plane.  Intermediate 
movements  always  stimulate  two  adjoining  pairs  of  canals  but  in  an 
unequal  degree.  There  is  this  to  be  remembered,  however,  that 
the  primary  sensation  arises  at  the  beginning,  when  the  movement  of 
the  canal  is  toward  the  ampulla  and  hence,  when  the  pressure  of  the 
endolymph  is  exerted  in  the  direction  from  the  utricle  toward  the 
other  extremity  of  the  canal.  Psychically,  therefore,  all  movements 
are  interpreted  correctly,  although  in  a  manner  opposite  to  the  position 
of  the  hair-like  processes.  The  secondary  dynamic  effect,  producing 
the  deviation  of  the  hairs  at  the  end  of  the  rotation,  does  not  stimulate 
unless  excessive.  In  the  latter  case,  a  sensation  of  rotation  is  produced 
in  a  direction  opposite  to  the  primary. 

Naturally,  the  labyrinthine  sensations  of  movement  are  augmented 
by  others  to  form  the  sense  of  equilibrium.  Chief  among  these  are 
the  sensations  of  position,  the  muscle-sense  and  the  sensations  of  sight 
and  touch.  Ewald  beheves  that  all  these  unite  in  regulating  the  tonus 
of  the  musculature  which  forms  the  basis  of  the  stability  of  our  body. 
If  the  body  sways  toward  one  side,  the  stimulation  of  the  hair  cells 
then  ensuing,  gives  rise  to  an  increase  in  the  tonus  of  the  muscles  ordi- 
narily counteracting  this  movement.  In  this  way,  the  labyrinthine 
reflexes  are  utiUzed,  together  with  others,  in  evoking  those  compensa- 
tory reactions  which  are  directly  responsible  for  our  orientation  in  space. 
This  point  has  found  substantiation  in  the  experiments  of  Magnus 
and  Klijn,^  made  upon  cats  during  the  condition  of  decerebrate 
rigidity.  The  muscles  of  the  extremities  having  been  rendered  rigid 
by  the  removal  of  the  cerebrum,  the  mere  tilting  of  the  head  of  the 
animal  sufficed  to  produce  perfectly  definite  changes  in  the  position 
of  its  limbs.  Besides,  these  compensatory  reactions  disappeared 
immediately  after  the  destruction  of  both  labyrinths. 

1  Pfliiger's  Archiv,  cxlv,  1912,  455. 


SECTION  XXIII 
THE  SENSE  OF  SIGHT 


CHAPTER  LXVII 

PHYSIOLOGICAL   OPTICS 

The  Nature,  Cause  and  Velocity  of  Light. — The  study  of  the 
phenomena  connected  with  hght,  and  their  application,  is  called  optics. 
Physiological  optics  is  that  subdivision  of  optics  which  deals  with 
these  phenomena  as  appHed  in  a  practical  way  to  our  visual  mechanism. 
In  accordance  with  Aristotle,  the  universe  consists  of  four  mundane 
elements,  earth,  fire,  water,  air  and  a  fifth  submundane,  or  ether. 
This  name  was  applied  to  this  element  on  account  of  its  ethereal  cir- 
cular movement  and  not  on  account  of  its  "fire."  At  the  present 
time,  of  course,  we  are  concerned  solely  with  those  ethereal  impacts 
which  give  rise  to  illumination,  and  particularly  with  those  which 
affect  the  retinae  of  our  eyes,  because,  as  commonly  understood,  light 
is  that  form  of  energy  which  by  its  action  upon  this  receptor,  evokes 
the  phenomenon  of  vision.  In  this  group  must  be  placed  the  ethereal 
vibrations  forming  the  spectral  colors,  namely,  vibrations  possessing 
a  rate  per  second  of  482,000,000,000,000  for  red  hght  and  of  707,000,- 
000,000,000  for  violet  hght. 

The  different  sources  of  light  may  be  divided  into  natural  and  artificial.  The 
most  important  among  the  former  is  the  sun.  Then  follow  the  fixed  stars,  nebulae, 
comets,  meteors,  lightning,  auroras  and  lights  modified  by  reflection  and  refraction, 
such  as  that  of  the  rainbow,  clouds,  and  phosphorescent  and  fluorescent  bodies. 
Among  the  artificial  sources  might  be  mentioned  the  combustions  of  gas,  oil,  wood, 
coal,  etc.,  and  the  illumination  produced  by  the  electric  current  and  mechanical 
impacts.  But,  since  we  are  dealing  in  the  latter  case  with  certain  forms  of  stored 
energy,  all  these  sources  of  light  must  have  had  originally  an  exherent  cause, 
presumably  the  sun. 

Regarding  the  cause  of  light  two  theories  have  been  propounded,  namely, 
the  emission  or  corpuscular  theory,  generally  accredited  to  Newton,  and  the  undula- 
tory  theory  of  Huyghens  and  Euler.  The  first  assumes  that  the  different  luminous 
bodies  actually  discharge  certain  particles  or  molecules  in  straight  lines.  Conse- 
quently, luminous  vibrations  are  really  transverse  in  their  direction,  while  those  of 
sound  are  longitudinal.  This  assumption  would  lead  us  to  infer  that  the  retina 
is  stimulated  by  actual  molecules  of  matter.  The  second  theory  holds  that  all 
space  is  filled  with  an  attenuated  medium,  called  luminiferous  ether,  which  is  set 
into  rapid  vibration.  This  conception  would  imply  that  the  retina  is  stimulated 
by  the  vibration  of  the  molecules  of  the  ether,  in  analogy  with  the  excitation  of 
the  organ  of  Corti  by  vibrations  or  waves  occurring  in  the  ordinary  atmosphere. 

794 


PHTSIOLOGICAL   OPTICS  795 

These  \'ibrations  in  ether  are  propaRated  at  an  almost  inoonreivably  rapid  rate. 
If  we  reckon  the  distance  of  the  earth  from  the  sun  at  91,ot}(),()00  miles,  the  speed 
of  sunlipiht  may  be  calculated  at  185,500  miles  in  a  second.  Thus,  it  would  require 
this  light  about  eight  minutes  to  reach  the  earth,  that  of  Neptune  about  four 
hours,  that  of  Centaurus  clo.se  to  4  years  and  that  of  Sirius  17  years.  Light 
therefore,  travels  with  a  velocity  which  Ls  900,000  times  greater  than  that 
of  sound;  moreover,  its  stimulating  power  is  extremely  great,  because  a  flash  of 
lightning,  lasting  fi.ooo-ooo  .sec,  suffices  to  produce  a  visual  .sensation.  SunUght, 
of  course,  is  the  strongest  light,  equalling  the  power  of  5500  candles  placed  at  a 
distance  of  one  foot.  It  is  600,000  as  strong  as  the  reflected  light  of  the  moon 
and  16,000,000,000  as  strong  as  that  of  Centaunis. 

In  passing  away  from  its  source,  light  is  brought  into  contact  with  difTerent 
bodies,  which  tend  to  hinder  its  course.  Only  the  most  perfect  vacuum  allows 
it  to  pass  with  as  much  freedom  as  the  air.  Other  media  are  classified  as  trans- 
parent, translucent  and  opaque.  Transparent  media  permit  of  the  pa.ssage  of 
white  light,  as  well  as  of  its  spectral  components,  so  that  any  object  may  be  seen 
through  them  in  its  different  colors.  Among  these  might  be  mentioned  the  air, 
water,  glass,  the  humors  of  the  eye,  and  others.  Translucent  bodies  allow  only  a 
certain  number  of  the  light  rays  to  pass,  so  that  a  clear  outline  of  the  objects 
cannot  be  obtained.  Opaque  bodies  cannot  give  rise  to  \'isual  sensations,  because 
they  prevent  the  passage  of  these  rays,  although  permeable  to  them.  The  light  is 
then  said  to  be  absorbed,  i.e.,  it  is  converted  into  some  other  form  of  energy,  such 
as  heat. 

Reflection. — Luminous  bodies  are  those  which  emit  hght,  such  as 
the  sun  or  substances  when  undergoing  combustion.  A  luminous  ray, 
therefore,  may  be  defined  as  the  direction  of  the  Hne  in  which  Hght  is 
propagated,  and  a  pencil  of  light  as  a  collection  of  rays  from  the  same 
source.  In  this  form,  it  consists  of  a  number  of  divergent  rays,  i.e., 
of  rays  which  in  passing  away  from  the  luminous  object,  gradually 
become  more  widely  separated  from  one  another.  A  beam  of  light 
includes  a  large  number  of  light  rays  showing  measurable  dimensions. 
It  embraces  divergent,  parallel  and  convergent  rays,  but  the  convergent 
rays  are  of  no  use  to  us  under  ordinary  conditions. 

If  light  is  made  to  pass  through  a  homogeneous  medium,  such  as 
air,  glass  or  water,  it  is  propagated  onward  in  a  right  line,  while  if  an 
opaque  body  is  placed  in  its  path,  it  will  be  intercepted  by  it  and 
be  absorbed  or  reverberated.  In  the  latter  case,  the  Hght  is  forced  to 
change  its  direction,  although  aUowed  to  continue  onward  in  the  same 
medium.  To  this  phenomenon  the  name  of  reflection  has  been  given. 
Reflecting  bodies  may  be  polished  or  unpolished.  The  first  give  rise 
to  regular  and  the  second  to  diffused  reflection.  Thus,  if  a  beam  of 
light  is  incident  upon  a  well-polished  mirror,  the  greater  part  of  the 
light  is  reflected  in  a  single  direction  at  a  perfectly  definite  angle; 
in  fact,  the  reflection  is  so  precise  that  it  may  be  said  to  be  governed 
by  two  laws,  as  follows: 

(1)  The  reflected  ray  BE  is  in  the  plane  of  the  incident  ray  DB  and  a  normal  or 
perpendicular  AB  erected  upon  the  reflecting  surface  CF  at  the  point  of  incidence 
B  of  the  ray  (Fig.  404). 

(2)  The  angle  EBA  formed  by  the  reflected  ray  and  the  perpendicular,  equals 
the  angle  DBA  made  bj'  the  incident  ra\'  and  the  perpendicular.  In  other  words, 
the  angle  of  reflection  is  equal  to  the  angle  of  incidence. 


796 


THE    SENSE    OF   SIGHT 


A  beam  of  light  falling  upon  an  unpolished  surface  suffers  a  reflec- 
tion of  its  rays  in  all  directions,  because  inasmuch  as  the  surface  is 
composed  of  projecting  particles  which  receive  incident  rays  at  all 
angles,  the  reflected  rays  must  be  diffused  or  scattered  in  all  directions. 
Naturally,  the  intensity  of  the  reflected  hght  is  always  less  than  that 
of  the  incident  light,  because  at  least  some  of  the  original  vibrations 

are  converted  into  vdbrations  of  the 
reflecting  surface.  Thus,  the  intensity 
of  the  reflected  light  really  depends 
upon  (a)  the  brilliancy  of  the  source  of 
light,  (b)  the  perfection  of  the  polish, 
(c)  the  angle  of  the  incident  ray,  {d) 
the  character  of  the  reflecting  sub- 
stance, and  (d)  the  character  of  the 
medium  in  which  the  reflection  is  tak- 
ing place. 


Fig.    404. — Reflection   from 
Plane  Mirrors. 


In  accordance  with  their  shape,  reflecting 
surfaces  may  be  classified  as  plane,  concave, 
convex,  spherical,  parabolic,  conical,  etc. 
The  reflection  from  a  plane  mirror  is  illustrated 
by  Fig.  404.  If  a  ray  of  light  emitted  by 
point  D,  meets  the  surface  CF  at  the  angle  DBA,  the  reflected  ray  forms  the  angle 
EBA.  The  eye  at  E  then  sees  the  image  of  D  as  if  it  were  placed  at  /,  this  point 
being  situated  where  the  prolongation  of  EB  intersects  the  perpendicular  drawn 
through  D.  Hence,  the  determination  of  the  position  and  size  of  images  formed 
by  plane  mirrors,  resolves  itself  into  a  determination  of  the  image  points  of  the 
several  different  luminous  points.  It  will  be  seen,  therefore,  that  the  image  is 
perceived  as  being  located  behind  the  mirror  at  a  distance  equal  to  that  of  the 
given  points. 


A 

B\ 

c^ 

f''  A 

£ 

\. 

\ 

Fig.  405. — Reflection  from  a 


Concave  Spherical  Mirror  if  Its  Incident  Ray  is 
Parallel. 


Spherical  mirrors  are  those  possessing  the  curvature  of  a  sphere, 
and  are  formed,  therefore,  by  the  revolution  of  an  arc  around  the  radius 
CD.  The  inner  concave  and  the  outer  convex  surface  may  of  course 
be  supposed  to  be  made  up  of  an  infinite  number  of  plane  mirrors. 
Reflection  may  take  place  from  the  former  as  well  as  from  the  latter. 
C,  the  center  of  the  hollow  sphere, ,  constitutes  the  geometrical  center 
or  center  oj  curvature,  while  a  Hne  drawn  through  C  and  D,  forms  the 


PHYSIOLOGICAL    OPTICS  797 

principal  axis  of  tliis  reflecting  surface.  Any  other  line  passing 
through  C  to  a  different  point  of  the  mirror  than  its  middh;,  consti- 
tutes a  secondary  axis.  The  perpendicular  of  each  of  the  small  planes 
forming  this  reflecting  surfacre,  is  the  radius  of  the  sphere  and  each 
reflected  ray  forms  with  the  corresponding  ratUus  the  same  angle  as 
the  incident  ray.  Thus,  all  rays  parallel  to  th(>  piincipal  axis  {AB  and 
EH,  Fig.  405)  are  brought  to  a  focus  at  the  principal  focus  F  midway 
between  C  and  D.  Quite  similarly,  all  rays  pursuing  a  course  parallel 
to  any  secondary  axis,  are  brought  to  a  focus  in  a  point  lying  on  this 
axis.  Hence,  if  the  princijml  focus  F  were  converted  into  a  luminous 
point,  the  raj^s  emitted  from  here  would  be  reflected  back  into  rays 
taking  their  course  parallel  to  the  principal  axis. 

If  the  luminous  point  L  is  situated  upon  the  principal  axis  at  a  distance  insuffi- 
cient to  render  the  rays  emitted  by  it  parallel,  then  the  divergent  incident  ray  LB 
(Fig.  406)  and  the  perpendicular  BC  form  the  angle  LBC.  This  angle  is  smaller 
than  that  formed  by  the  parallel  ray  AB  with  the  corresponding  normal  BC;  and 
hence,  it  may  l)e  inferred  that  the  angle  of  reflection  of  a  divergent  ray  is  smaller 
than  the  angle  of  reflection  of  a  parallel  ray.  Consequently,  the  principal  focus 
of  L  must  lie  in  L'  between  F  and  C;  i.e.,  between  the  center  of  curvature  and  the 


Fig.  406. — Reflection   from  a  Concave  Spherical  Mirror  if  its  Incident  Ray   is 

Divergent. 

principal  focus  F.  By  converting  L^  into  a  luminous  point,  the  rays  may  in  the 
same  manner  be  reflected  outward  into  L.  The  latter,  therefore,  may  be  said  to 
be  the  conjugate  focus  of  L^.  It  will  then  be  seen  that  if  the  luminous  point  L  is 
placed  in  the  center  C,  the  angle  of  incidence  is  null  and  the  angle  of  reflection  null. 
Consequently,  the  ray  is  reflected  upon  itself  so  that  its  focal  point  coincides  with 
the  luminous  point.  Lastly,  if  the  luminous  point  L  is  situated  between  the  center 
of  rotation  C  and  the  principal  focus  F,  the  conjugate  focus  must  be  on  the  other 
side  of  the  center  and  the  farther  from  it,  the  shorter  the  distance  between  L  and 
the  principal  focus.  These  principles  find  their  application  in  the  explanation  of 
Purkinje's  image  reflected  from  the  concave  anterior  surface  of  the  vitreous  humor. 

The  reflection  from  convex  spherical  surfaces  finds  its  appUcation  in  the  images 
formed  upon  the  anterior  surfaces  of  the  cornea  and  lens.  Supposing  that  the 
entering  ray  pursues  a  course  parallel  to  the  principal  axis  of  the  convex  mirror, 
its  reflection  from  the  latter  will  give  to  it  a  divergent  course.  If  the  reflected  ray 
is  continued  by  an  imaginary  line  through  the  mirror,  it  will  be  seen  to  strike  the 
principal  focus  at  F  which  is  approximately  the  center  of  the  radius  of  curvature 
CD  of  this  mirror. 

The  images  formed  by  rays  of  light  differ  with  the  direction  assumed  by  them 
after  their  reflection.  When  they  converge,  as  after  their  reflection  by  concave 
mirrors,  they  form  a  real  image  in  front  of  the  mirror  and  on  the  same  side  as  the 


798 


THE    SENSE    OF   SIGHT 


object.  A  real  image,  therefore,  is  produced  by  the  reflected  rays  themselves,  and 
may  be  observed  with  the  aid  of  a  screen  properly  adjusted  at  their  points  of  inter- 
section. Divergent  rays,  on  the  other  hand,  are  supposed  to  be  projected  directly 
through  the  mirror  and  are  seen  as  if  they  proceeded  from  its  other  side.  In 
the  latter  case,  the  image  has  no  real  existence,  but  is  effected  by  the  prolon- 
gations of  the  reflected  rays  backward.  This  is  called  a  virtual  image.  _  Obviously, 
therefore,  a  real  foms  is  formed  by  the  reflected  rays  themselves,  while  a  virtual 
focus  is  formed  by  their  prolongations  backward  through  the  mirror. 

Refraction. — If  a  ray  of  light  is  made  to  pass  from  one  medium 
into  another  in  a  perpendicular  direction,  it  is  not  deviated  from  its 
course.  The  contrary  result,  however,  is  obtained  if  it  is  made  to 
enter  in  an  obhque  direction.  To  this  phenomenon  the  term  of 
refraction  has  been  applied.  It  is  to  be  remembered  that  not  all  the 
rays  of  a  certain  beam  of  light  are  refracted,  because  some  of  them  are 
reflected  from  the  surface  in  accordance  with  the  character  of  the 
medium  into  which  they  have  been  directed.  Those  that  actually 
enter  the  denser  medium  are  refracted, because  their  velocity  of  pro- 
pagation is  now  less  than  it  was  in  the  rarer  medium.  The  degree 
of  refraction  differs  with  the  relative  densities  of  the  two  media. 
Supposing  that  we  are  deahng  with  air  and  water  separated  by  a  thin 


Fig.   407. — Diagram  Illustrating     Fig.  408. — Diagram  Illustrating  Refraction. 
Refraction. 

layer  of  glass  (Fig.  407),  it  will  be  found  that  any  ray  directed  verti- 
cally to  the  surface  of  the  latter  (AB),  is  not  deviated  from  its  course 
{BC).  Any  incident  ray,  however,  which  strikes  the  surface  of  the 
water  obliquely  (DB),  is  deflected  (BE)  toward  the  perpendicular 
AC.  The  angle  of  incidence  ABD^  is  then  larger  than  the  angle  of 
refraction  CBE,  and  naturally,  this  angle  becomes  the  smaller,  the 
greater  the  refracting  power  or  density  of  the  second  medium.  The 
ratio  between  the  angle  of  incidence  and  the  angle  of  refraction  con- 
stitutes the  index  of  refraction.  When  passing  in  the  opposite  direc- 
tion (Fig.  408),  namely  from  a  medium  of  greater  into  one  of  lesser 
density  or  refractive  power,  the  ray  BE  is  bent  away  from  the  perpen- 
dicular rendering  the  angle  of  refraction  greater  than  the  angle  of 
incidence.  Thus,  taking  the  index  from  air  to  water  to  be  ^  and  from 
air  to  glass  ^^,  the  course  of  the  ray  in  the  opposite  direction  would 
show  an  index  of  ^^  and  ^^  respectively. 

The  first  law  of  refraction  states  that  the  refracted  ray  is  in  the 


PHYSIOLOGICAL   OPTICS 


799 


same  plane  as  the  incident  ray  antl  the  perpendicular  drawn  to  the 
surface,  separating  the  two  media.  The  second  law  is  that  the  ratio 
which  the  line  of  the  incident  ray  bears  to  the  line  of  the  angle  of 
refraction,  is  constant  for  the  same  two  media  but  different  for  differ- 
ent media.  ^ 

Refractive  media  may  be  bounded  bj': 

(a)   Two  plane  surfaces  which  are  parallel  to  one  another.     A  ray  impinging 
upon  a  plate  at  a  right  angle,  traverses  this  medium  without  suffering  a  change  in 


Fig.  409. — Diagram  Il- 
lustrating IIefr.\ction  by 
A  Plate- LIKE  Body. 


Fig.    410. — Diagram    Illus- 
trating Refraction  by  Prisms. 


its  direction.  Any  other  ray  DB  meeting  this  surface  at  an  angle,  is  bent  toward 
the  perpendicular  AB  on  entering,  but  away  from  it  on  leaving  the  medium.  The 
emergent  ray  EF  is  parallel  to  the  incident  ray  (Fig.  409). 

(6)  Two  plane  surfaces  which  incline  toward  one  another.  At  the  point  of 
intersection  of  these  two  surfaces  is  the  summit  or  apex  A.  Their  inclination 
constitutes  the  refractive  angle  and  their  right  line  BC  the  base.  The  medium  so 
outlined  is  a  prism  (Fig.  410).  A  ray  of  light  LE  impinging  upon  one  of  its  lateral 
surfaces  AB,  is  deflected  toward  the  normal  P  at  E,  because  it  passes  into  a  more 
highly  refractive  medium.     It  here  forms  the  angle  of  incidence  LEB  and  the  angle 


12  3  4  5  6 

Fig.  411. — Different  Forms  of  Convex  and  Concave  Lenses. 

of  refraction  lEF.  When  meeting  with  the  other  surface  ^C  it  is  again  refracted, 
the  angle  of  refraction  HFK  being  greater  than  the  angle  of  incidence  EFI;  because 
it  passes  from  a  more  highly  refractive  medium  into  one  of  less  power.  Thus,  the 
ray  is  deflected  from  its  course  in  the  direction  of  the  base  of  the  prism.  In  this 
case,  the  image  of  L  is  produced  at  S,  in  the  prolongation  of  the  emerging  ray. 

(c)  Two  surfaces  one  of  which  is  either  curved  or  plane.  The  refractive  medium 
is  thus  arranged  in  the  form  of  a  lens  which  in  accordance  with  its  shape  may  be 
spherical,  cylindrical,  elliptical  or  parabolic.  In  optics  spherical  lenses  are  most 
commonly  employed  and  they  may  be  made  of  crown  glass  or  flint  glass.  The 
former  is  free  from  lead  and  is  therefore  less  refractive  than  the  latter  which  contains 
lead.     By  combining  spherical  surfaces  either  with  plane  or  curved  surfaces,  six 

^  Stated  by  Snell  in  1620,  but  enunciated  by  Descartes. 


800 


THE    SENSE    OF    SIGHT 


different  kinds  of  lenses  are  obtained,  namely  (a)  plano-convex,  (6)  biconvex, 
(c)  concavo-convex,  (d)  plano-concave,  (e)  biconcave  and  (/)  concavo-convex 
(Fig.  411).  The  lens  in  our  eye  is  a  double  convex  or  biconvex  lens,  but  we  shall 
have  occasion  to  refer  to  the  other  types  of  lenses,  as  well  as  to  prisms  and  planes 
when  discussing  errors  in  refraction  and  their  correction. 

Refraction  by  a  Biconvex  Lens. — A  biconvex  lens  is  essentially 
the  segment  formed  at  the  intersection  of  two  spheres  drawn  upon  the 
same  Hne  with  either  the  same  or  different  radii  (Fig.  412).     Hence, 


Fig.  412.  Fig.  413. 

Fig.  412. — Diagram    Illustrating    the    Formatiox    of    Bicon-\t;x     Leks.. 
Fig.  413. — Structure  of  Bicon\'ex  Lens.      (From  Draper  "  Medical  Physics.") 

a  line  prolonged  through  the  centers  of  curvature  of  the  two  surfaces 
of  this  lens  (AB),  must  form  the  principal  axis  of  this  system.  Be- 
tween these  two  centers  lies  a  point  C  which  possesses  the  property  of 
permitting  rays  to  pass  without  refraction,  so  that  the  emergent  ray 
is  parallel  to  the  incident  ray.  This  point  constitutes  the  optical 
center  of  the  lens.  Any  other  line  passing  through  this  center  is  a 
secondary  axis. 

The  action  of  a  biconvex  lens  upon  the  entering  rays  of  light  is  easily  understood 
if  the  lens  is  imagined  to  be  composed  of  a  number  of  prisms  arranged  in  the  manner 


Fig.  414. — Cox\'Ex   Lex.s    Dissected.     (From   Draper   "Medical  Physics.") 

indicated  in  Fig.  413.  It  will  be  remembered  that  a  prism  deflects  or  deviates  the 
ray  toward  its  base;  hence,  a  biconvex  lens  deflects  the  entering  rays  in  accordance 
with  the  refractive  power  of  its  prismatic  constituents.  Inasmuch  as  the  central 
prisms  d,  e,  etc.,  have  a  smaller  refracting  angle  than  the  outer  one  /  and  g,  they 
must  give  rise  to  a  lesser  deviation.  The  same  holds  true  of  the  prismatic  elements 
situated  above  the  principal  axis,  and  whether  in  the  vertical,  horizontal  or  oblique 
meridian  of  this  lens.  Their  tips  are  of  course  directed  outward  and  their  bases 
inward;  and  furthermore,  the  central  ray  following  the  line  of  the  principal  axis, 
is  not  deflected  at  all     It  will  be  seen,  therefore,  that  a  biconvex  lens  possessing 


PHYSIOLOGICAL    OPTICS  801 

properly  centered  prisms,  converges  Ihe  previously  divcrKont  rays,  so  that  hiini- 
nous  i^oiiit  .1  is  hrounlit  to  n  precise  focus  in  C  upon  the  priiicipnl   axis. 

In  ascertaining^  (lie  formation  of  an  imaf>;e  hy  a  doul)le  (•(nivex  lens,  it  must  be 
remembered  (hat  ail  objects  ])()ssess  numerous  luminous  points,  (he  rays  emitted  by 
them  beinjj;  collected  by  (he  lens  into  a  corresponding  number  of  foci.  This  implies 
that  under  ordinary  conditions,  the  ima^e  furnished  by  a  biconvex  lens,  is  real. 
Supposing  that  we  are  dealing  with  a  biconvex  lens  of  the  refractive  power  of  the 
lens  of  our  eye,  and  ])lace  an  object  in  front  of  it  at  a  distance  of  more  than  twenty 
feet,  then  the  object  emits,  among  others,  a  large  number  of  rays  which  pursue  a 
course  parallel  to  the  principal  axis  of  this  lens  {AH  etc..  Fig.  41.5).  All  these  ray.s 
are  converged  to  very  nearly  (h(>  same  focus  F  upon  the  jirineipal  axis.     The  dis- 


FiG.  415. — Diagram  Illustrating  the  Refraction  of  Parallel  Rays  by  a  Biconvex 

Lens. 

tance  LF,  is  known  as  the  principal  focal  distance.  If  the  object  is  now  moved 
farther  away  from  the  lens,  the  -principal  focus  F  moves  toward  thelens,  while  if 
the  object  is  placed  nearer  the  lens  but  not  close  enough  to  render  the  rays  diver- 
gent, the  focal  point  F  moves  farther  backward.  Lastly,  if  F  itself  is  rendered 
luminous,  the  rays  emitted  from  here  traverse  the  lens  in  the  opposite  direction 
and  leave  its  anterior  surface  parallel  to  the  principal  axis.  This  is  merely  a  re- 
versal of  the  previous  condition  in  which  parallel  rays  are  brought  to  a  focus  in  F. 
If  a  luminous  point  L  is  placed  upon  the  principal  axis  at  a  distance  greater 
than  the  focal  distance  of  this  lens,  but  not  far  enough  from  it  to  cause  its  rays  to 
become  parallel,  then  the  rays  diverging  from  it  are  brought  to  focus  in  L^,  at  a 


Fig.  416. — Diagram  Illustrating  the  Refraction  of  Divergent  Rays  by  a  Biconvex 

Lens. 

point  beyond  the  principal  focus  F  (Fig.  416).  In  case  L^  is  now  rendered  lumi- 
nous, its  rays  are  brought  to  a  focus  in  L.  For  this  reason,  these  points  are  com- 
monly spoken  of  as  conjugate  foci.  By  moving  luminous  point  L  nearer  to  and 
farther  away  from  the  lens,  the  focal  point  L^  may  be  made  to  move  first  farther 
away  and  then  nearer  to  the  lens.  In  the  first  case,  a  point  will  be  reached  when 
the  emerging  rays  finally  become  so  greatly  divergent  that  they  cannot  be  focalized 
at  all  (Fig.  417).  This  effect  appears  whenever  the  luminous  point  L  is  situated 
nearer  the  lens  than  its  principal  focal  distance.  In  this  case,  a  virtual  focus  is 
formed  at  L^,  at  the  intersection  of  the  prolongations  of  the  emerging  rays. 

If  rays  are  directed  into  this  lens  which  are  already  convergent,  their  conver- 
gence is  simply  increased  so  that  their  focal  point  comes  to  lie  nearer  the  lens  than 
£1 


802 


THE    SENSE    OF   SIGHT 


it  would  if  the  rays  entering  it  had  been  parallel.  This  is  the  function  of  the 
cornea.  It  tends  to  gather  the  slightly  divergent  rays  and  to  render  them  available 
for  refraction  by  the  lens.  This  discussion  shows  that  if  an  object,  even  a  very 
large  one,  is  placed  at  a  sufficient  distance  from  a  biconvex  lens,  a  small  real  and 
inverted  image  of  it  is  formed  just  outside  the  principal  focus  F.     The  greater  the 


Fig.  417. 


-Diagram  Illustrating  the  Refraction  of  Extremely  Divergent  Rats  by 
A  Biconvex  Lens 


distance,  the  smaller  this  image.  This  principle  is  illustrated  by  our  eye  as  well  as 
by  the  ordinary  photographic  camera.  Quite  similarly,  one  small  object  placed 
upright  just  outside  the  principal  focal  point  F  of  a  biconvex  lens,  forms  a  large 
inverted  image  at  a  considerable  distance  in  front  of  the  lens.  This  principle  is 
illustrated  by  the  projection  lantern. 


Fig.  418. — Diagram  Illustrating   Formation  of  an  Image  by  a  Biconvex    Lens. 

In  constructing  the  image  of  an  object  AB  as  formed  by  a  biconvex  lens,  it  must 
be  remembered  that  one  ray  ^D  emitted  by  luminous  point  A,  always  traverses  the 
nodal  point  of  the  lens  A''  unrefracted  and  that  a  second  ray  A £■  enters  the  lens  paral- 
lel to  its  principal  axis  (Fig.  418).  The  ray  AE'is  then  refracted  through  the  focal 
point  F.     The  focal  point  of  A  lies  at  the  point  of  intersection  of  these  two  hnes. 


Fig.  419. — Diagram  Illustrating  the  Refraction  by  a  Biconcave  Lens. 


If  this  construction  is  now  extended  to  a  luminous  point  B  upon  the  lower  end  of  the 
object  AB,  it  will  be  seen  that  this  one  is  brought  to  a  focus  al:)ove.  Consequently, 
the  image  of  object  AB  is  inverted.  In  those  cases  in  which  the  object  is  placed 
between  the  biconvex  lens  and  its  principal  focus,  only  virtual  erect  images  are 
formed  This  principle  is  made  use  of  in  the  construction  of  microscopes  and 
magnifying    glasses. 


THK    (JLOHK    OF    THE    P:YE  803 

Refraction  by  a  Biconcave  Lens. — To  undorstand  the  rofraction 
by  biconcave  lenses,  imagine  tlie  lens  to  be  composed  of  a  number  of 
prisms,  which  in  cross-section  have  their  apices  directed  toward  the 
center  or  axis  of  the  lens  and  their  bases  toward  the  peiiphery.  If 
we  remember  that  the  rays  entering  the  incUnation  of  a  prism,  are 
deflected  toward  its  base,  it  must  be  evident  that  a  biconcave;  lens 
renders  the  rays  divergent  (Fig.  419).  Like  the  concave  mirrors, 
these  lenses  give  rise  to  virtual  images.  When  the  incident  ray  meets 
the  anterior  surface  of  this  lens,  it  is  refracted  toward  the  perpendicular, 
CB,  but  away  from  it  at  H.  This  double  refraction  also  takes  place 
with  every  other  ray,  for  example,  with  DE  and  hence,  there  is  no  real 
focus  established.  The  prolongations  of  these  rays  intersect  in  F 
which  is  the  principal  virtual  focus. 


CHAPTER  LXVIII 


THE  GLOBE  OF  THE  EYE  AND  ITS  PROTECTIVE 
APPENDAGES 

The  General  Structure  of  the  Eyeball. — The  eyeball  is  placed  in 
the  fore  part  of  the  orbital  cavity  and  is  adjusted  in  such  a  way  that  it 
may  be  activated  by  almost  any  ray  projected  toward  it.  Its  range  is 
greatly  increased  by  the  fact  that  it  may  be  moved  in  different  direc- 
tions by  means  of  muscles  attached  to  its  external  coat.  In  the  mam- 
mals, the  visual  mechanism  consists  of  two  eyeballs  and  their  connec- 
tions with  the  centers  for  vision  in  the  occipital  cortex  of  the  cerebrum. 
This  implies  that  these  animals  are  in  possession  not  only  of  a  most 
highly  developed  receptor,  but  also  of  the  means  of  forming  the  best 
possible  concepts.  In  this  regard  they  are  sharply  differentiated  from 
the  lower  forms  which,  although  equipped  with  receptors  of  sufficient 
sensitiveness  toward  the  ethereal  impacts,  are  quite  unable  to  asso- 
ciate them  properly,  because  they  lack  the  central  organ  essential  for 
this  function.  Many  of  the  lower  forms  are  able  to  perceive  Hght  by 
means  of  their  pigment  spots  and  other  cutaneous  sense-organs,' 
but  react  toward  it  merely  in  a  reflex  way,  by  displaying  phenomena 
similar  to  the  heliotropism  or  phototaxis  of  the  lowest  organisms. 
In  a  way,  these  forms  are  really  in  the  same  position  as  we  would  be 
if  our  eyehds  were  kept  permanently  closed,  because  although  still 
able  to  appreciate  differences  in  the  intensity  of  the  illumination,  we 
would  then  react  in  accordance  with  these  and  no  longer  depend 
upon  distinct  visual  impressions  and  concepts. 

A  much  more  advanced  state  of  development  is  attained  by  the 
eye  of  the  higher  invertebrates.  That  of  the  insects  is  composed  of 
^  Hesse,  Das  Sehen  der  niederen  Tiere,  Jena,  1908. 


804 


THE    SENSE    OF    SIGHT 


numerous  funnel-shaped  tubules,  through  which  the  rays  of  light  are 
refracted  by  means  of  a  lens-like  structure  of  chitin.  This  type  of  eye, 
however,  is  soon  abandoned,  because  already  in  the  cephalopods  we 
find  a  single  system  of  curved  refracting  media.  In  the  vertebrates 
the  eye  is  constructed  along  very  similar  lines.  Retrogressive  it 
becomes  in  proteus  and  sphalax,  because  these  animals  live  perma- 
nently in  the  dark. 

The  eye  is  the  organ  of  space,  its  purpose  being  to  form  images 
of  external  objects  upon  the  retina  which  are  then  conveyed  into 
consciousness.     Its  general  structure  and  manner  of  action  reminds 


Fig.  420. — DiAGR.\jii  of  a  Horizontal  Section  Through  the  Human  Eye. 

C,  cornea;  A,  anterior  ca\'ity;  P,  posterior  ca-\aty ;  Z,  lens;  J ,  iris;  T,  conjunctival  sac; 
CL,  ciliary  ligament;  CB,  ciliary  body;  CM,  ciliary  muscle;  OS,  ora  serrata;  CS,  canal  of 
Schlemm;  R,  retina;  Ch,  choroid;  S,  sclera;  ON,  optic  nerve;  A,  retinal  artery;  B,  blind 
spot;  Y,  yellow  spot;  OA,  optical  axis;  VA,  visual  axis;  H,  hyaloid  canal. 

us  of  the  camera  obscura,  the  box  of  which  is  represented  by  the  cor- 
neal and  sclerotic  envelope  of  the  eyeball,  its  refracting  medium  by  the 
aqueous  humor,  lens  and  vitreous  humor,  its  diaphragm  by  the 
iris,  and  its  sensitive  screen  by  the  retina.  Its  most  essential  constitu- 
ent is,  of  course,  the  retina,  while  its  other  structures  merely  serve  the 
purpose  of  adjuncts  to  effect  a  proper  concentration  of  the  rays  of  light. 
The  eyeball  is  spheroid  in  shape  and  is  loosel}"  held  in  the  orbital 
cavity  by  a  fibrous  membrane,  known  as  the  capsule  of  Tenon.  Its 
anteroposterior  diameter  measures  about  24  mm.,  and  its  transverse 
and  vertical  diameters  about  22  mm.  In  longitudinal  section  it  is 
seen  to  be  composed  of  the  segments  of  two  spheres,  of  which  the  pos- 


THE    (iLOBE    OF    THE    EYE  805 

terior  occupios  fivo-sixtlis  and  tlu^  anterior  one-sixth  of  tho  entire 
spheroid.  At  about  the  hue  of  junction  of  tliese  segments  is  phiced  a 
partition  consisting  of  the  ciHary  l)ody,  iris  and  lens.  In  this  way,  the 
ca\aty  of  the  eyeball  is  subdivided  into  two,  known  respectively  as  tho 
anterior  and  posterior  cavities.  The  former  is  fillcKl  with  acjueous 
humor  and  tiie  latter  with  vitreous  humor.  It  is  also  to  Ik;  noted  that 
the  wall  enclosing  the  former  is  in  part  translucent  (cornea),  whereas 
that  of  the  latter  is  opaque. 

The  Minute  Structure  of  the  Eyeball. — The  shell  of  the  eyeball 
consists  of  three  layers  airanged  concentrically  as  an  external,  a 
middle  and  an  internal  coat.  The  outermost  or  sclera  is  made  up  of 
dense,  tough,  opaque  fibrous  tissue  which  is  interwoven  with  elastic 
fibers  and  is  distributed  longitudinally  and  transversely  around  the 
eyeball.  If  the  e3'clids  are  widely  separated,  its  anterior  zone  appears 
as  the  "white  of  the  eye."  In  children  it  has  a  bluish  color,  owing 
to  the  fact  that  it  is  not  sufficiently  thick  to  prevent  the  dark  choroidal 
pigment  from  showing  through.  It  is  thickest  posteriorly  (1.0  mm.) 
at  the  entrance  of  the  optic  nerve,  and  thinnest  (0.4  mm.)  about  6  mm. 
from  the  cornea.  Anterior  to  this  point  it  is  again  thickened  to  give 
attachment  to  the  tendons  of  the  recti  muscles.  The  optic  nerve  and 
the  retinal  blood-vessels  pierce  the  sclera  about  2.5  to  3  mm.  internal 
to  the  posterior  pole  of  the  eyeball  and  about  1  mm.  below  the  hori- 
zontal line  uniting  its  anterior  and  posterior  poles.  By  virtue  of  its 
firmness,  the  sclera  serves  to  retain  the  shape  of  the  eyeball  and  to 
protect  its  soft  internal  structures.  In  this  it  is  aided  by  the  fact  that 
the  humors  of  the  eye  are  held  under  a  certain  pressure  which  is  desig- 
nated as  the  intraocular  pressure. 

The  cornea  which  is  really  the  modified  anterior  segment  of  the  sclerotic  coat, 
is  transparent  and  allows  the  rays  of  light  to  enter  the  interior  of  the  eye.  Looked 
at  from  in  front,  it  possesses  a  nearh'  circular  outline,  measuring  about  12  mm.  in 
its  transverse  and  11  mm.  in  its  vertical  diameter.  In  infants,  its  central  zone 
is  generally  somewhat  thicker  than  its  marginal,  while  in  the  adult  it  is  somewhat 
thinner!  (0.45  to  1.37  mm.).  Its  curvature  is  less  than  that  of  the  sclerotic,  but 
varies  in  different  persons  as  well  as  at  difTerent  periods  of  their  life;  moreover, 
its  curvature  is  generally  greater  in  its  vertical  than  in  its  horizontal  meridian. 

The  substance  of  the  cornea  is  made  up  of  modified  connective  tissue  which  Ls 
continuous  with  that  forming  the  sclera.  Its  anterior  surface  is  enveloped  by 
stratified  epithelium  which  is  supported  by  a  structureless  membrane,  known  as 
the  anterior  homogeneous  lamella.  Its  posterior  aspect  is  covered  by  a  simple 
layer  of  endothelial  cells  situated  upon  the  posterior  homogeneous  lamella.  The 
latter  is  a  very  resistant  membrane,  as  may  be  gathered  from  the  fact  that  it  serves 
as  a  barrier  to  inflammatory  processes.  In  addition,  it  prevents  the  absorption 
of  the  aqueous  humor  through  the  corneal  lymphatic  spaces.  Close  to  the  margin 
of  the  cornea,  this  membrane  breaks  up  into  a  number  of  interconnected  lamellae 
which  either  serve  as  attachments  to  the  ciliary  muscle  or  are  prolonged  backward 
into  the  substance  of  the  iris  and  sclera.  The  fissures  in  between  these  lamella 
are  known  as  the  spaces  of  Fontana.  They  communicate  freely  with  the  anterior 
cavity  of  the  eye  as  well  as  with  the  canal  of  Schlemm,  a  circular  tube  traversing 
the  substance  of  the  sclera,  close  to  its  junction  with  the  cornea.     The  latter  is 

1  Blbc,  Monatsblatt  fiir  Augenheilkunde,  1872. 


806  THE    SENSE    OF   SIGHT 

generally  regarded  as  a  sinus-like  vein  which  serves  as  a  drainage  tube  for  the 
aqueous  humor.  ^ 

The  cornea  is  not  provided  with  blood-vessels,  excepting  along  its  margin,  where 
the  conjunctival  and  sclerotic  capillaries  form  superficial  and  deep  networks. 
Furthermore,  since  this  structure  is  also  devoid  of  lymphatics,  its  nutrition  must 
be  effected  by  the  lymph  contained  in  its  connective-tissue  spaces.  It  need  scarcely 
be  emphasized  that  this  arrangement  is  of  great  functional  importance,  because  it 
enables  the  rays  of  light  to  gain  the  pupillar  aperture  without  being  unduly  de- 
flected from  their  course.  The  nerve  fibers  of  the  cornea  are  derived  from  the 
plexus  annularis  surrounding  its  margin.  ^  From  here  these  fibers  strive  radially 
into  its  fibrous  substance,  where  they  form  secondary  plexuses  in  the  anterior 
and  posterior  laminated  structures.  The  fibers  of  these  inner  networks  are 
non-meduUated. 

The  choroid  is  in  firm  contact  with  the  internal  surface  of  the  sclera.  It  is  dark 
brown  in  color  and  extends  forward  to  a  point  very  near  the  cornea  where  it 
terminates  in  the  iris.  The  latter  appears  as  a  transverse  fold  which  is  attached 
to  the  eyeball  at  its  circumference,  but  is  otherwise  freely  suspended  in  the  aqueous 
humor  in  front  of  the  lens.  It  will  be  seen,  therefore,  that  this  membranous  par- 
tition divides  the  anterior  cavity  of  the  eyeball  into  two  compartments,  called 
respectively  the  anterior  and  posterior  chambers  of  the  eye.  The  former  is  bounded 
by  the  cornea  and  anterior  surfaces  of  the  iris  and  lens,  and  the  latter  by  the  poste- 
rior surface  of  the  iris  and  anterior  surface  of  the  lens.  Directly  behind  the 
iris,  the  choroid  is  folded  a  number  of  times  into  a  circular  thickening  which  ex- 
tends into  the  anterior  part  of  the  vitreous  humor.  This  structure  is  known  as  the 
ciliary  body  and  contains  the  ciliary  muscle.  Its  inner  pole  gives  attachment  to 
the  ciliary  ligaments  which  extend  from  here  to  the  capsule  of  the  lens.  The 
function  of  these  minute  parts  will  be  more  fully  discussed  later  on  when  studying 
the  process  of  accommodation.  The  choroid  consists  chiefly  of  an  extensive  rami- 
fication of  blood-vessels  held  in  place  by  delicate  strands  of  connective  tissue. 
These  vessels  are  principally  derived  from  the  ophthalmic  artery  and  pierce  the 
sclera  externally  to  the  entrance  of  the  optic  nerve.  They  are  known  as  the  short 
posterior  ciliary,  the  long  posterior  ciliary,  and  the  anterior  ciliary  arteries. 

The  retina,  forming  the  innermost  coat  of  the  eye,  extends  forward  to  almost 
the  ciliary  body.  It  terminates  in  this  region  in  a  dentated  border,  known  as  the 
ora  serrata.  Externally,  its  hexagonal  pigmented  cells  lie  in  close  contact  with 
the  choroid;  in  fact,  since  these  cells  most  generally  remain  adherent  to  the  latter, 
when  the  retina  is  peeled  off,  they  are  commonly  regarded  as  a  constituent  of  the 
middle  coat.  It  will  be  shown  later  on,  however,  that  they  are  more  intimately 
related  to  the  retina  and  should,  therefore,  be  considered  as  a  part  of  this  membrane. 
The  thickness  of  the  retina  diminishes  gradually  from  behind  forward,  measuring 
0.4  mm.  at  the  yellow  spot  and  0.1  mm.  at  the  ora  serrata.  When  in  a  perfectly 
fresh  condition,  it  exhibits  a  pink  color  and  appears  translucent  against  the  hyaline 
external  investment  of  the  vitreous  humor.  Its  blood-supply  is  derived  from  the 
arteria  centralis  retinaj,  a  branch  of  the  ophthalmic  which  enters  the  eyeball  to- 
gether with  the  fibers  of  the  optic  nerve,  and  then  subdivides  in  a  radial  manner 
until  its  terminals  reach  the  ora  serrata.  The  microscopic  structure  of  the  retina 
will  be  more  fully  discussed  later  on  in  connection  with  its  function. 

The  Eyelids. — The  closure  of  the  eyelids  is  effected  (o)  volitionally 
at  irregular  intervals,  (6)  involuntarily  at  rather  regular  intervals, 
(c)  reflexly  in  consequence  of  the  excitation  of  the  trigeminus  terminals 
innervating  the  structures  in  the  vicinity  of  the  eyeball,  {d)  reflexly 
on  account  of  the  stimulation  of  the  optic  nerve  by  high  intensities  of 
light,  and  (e)  during  states  of  cerebral  depression  and  sleep.     The  mus- 

^  Dogiel,  Anat.  Anzeiger,  1890. 

^  Leber  and  Gidzecker,  Archiv  fiir  Ophthalm.,  Ixiv,  1906. 


THE    GLOBE    OF   THE    EYE  807 

cle  involved  in  this  process,  is  the  orbicularis  palpebrarum  which  de- 
rives its  innervation  from  the  facial  nerve.  The  closure  of  the  upper 
lid  is,  of  course,  greatly  facilitated  by  gravity.  Tiu;  opening  of  the 
eyelids  is  effected  by  the;  uiusc.  levator  palpebrarum  which  raises  th(? 
upper  lid,  while  the  lower  lid  is  carrietl  downward  by  gravity.  The 
latter  may  be  depressed  still  further  by  the  contraction  of  the  muse, 
rectus  inferior,  because  the  tendon  of  this  muscle  and  the  inferior 
tarsus  are  connected  with  one  another  by  strands  of  connective  tissue. 
This  extra  depression,  however,  is  only  made  necessary  when  objects 
in  the  lower  visual  fields  are  to  be  observed  while  the  head  is  held  erect. 

In  many  fish,  amphibia  and  reptilia,  the  eye  is  completely  covered 
by  a  transparent  skin,  while  others,  such  as  the  sharks,  crocodiles 
and  birds,  are  in  possession  of  a  third  lid  which  moves  transversely 
across  the  cornea  from  its  inner  angle.  This  so-called  nictitating 
membrane  is  represented  in  the  mammals  by  the  phca  semilunaris. 
In  either  case,  the  eyelids  serve  primarily  as  a  mechanism  of  protection 
against  high  intensities  of  light  and  impacts  of  different  kinds.  Under 
ordinary  circumstances,  their  edges  are  separated  by  a  cleft  measuring 
about  28  mm.  in  height.  The  intervening  space  is  known  as  the 
rima  palpebraris.  Inasmuch  as  the  size  of  the  eyeball  does  not  vary 
very  considerably  in  different  individuals,  the  fact  that  an  eye  appears 
either  large  or  small,  is  chiefly  dependent  upon  variations  in  the  height 
of  this  cleft. 

The  Lacrimal  Glands  and  Their  Secretion. — The  internal  surfaces 
of  the  eyelids  are  lined  with  mucous  membrane,  which  is  reflected 
upon  the  anterior  aspect  of  the  eyeball.  This  lining  is  known  as  the 
conjunctiva  and  the  space  between  its  layers  as  the  conjunctival  sac. 
The  latter  is,  of  course,  chiefly  potential,  because  the  hds  are  firmly 
apphed  to  the  eyeball  and  their  surfaces  are  moistened  with  the  se- 
cretion of  the  lacrimal  gland.  This  gland  presents  a  compound 
tubuloracemose  character,  and  resembles  the  serous  salivary  glands.^ 
The  cytoplasm  of  these  cells  contains  two  kinds  of  elements,  namely, 
small  dark  granules  and  large,  clear,  vacuolar  formations  which 
greatly  increase  in  number  during  their  resting  period.  If,  on  the 
other  hand,  the  secretory  nerve  of  this  gland  is  stimulated  or  if  lacri- 
mation  is  evoked  by  means  of  pilocarpin,  these  clear  bodies  disappear, 
while  the  dark  granules  increase  in  number.  The  nerve-fibers  inner- 
vating this  gland,  are  derived  from  two  sources,  namely,  from  the 
lacrimal  branch  of  the  ophthalmic  (facial)  and  from  the  sympathetic.^ 

This  gland  occupies  the  upper  and  outer  extent  of  the  orbital 
cavity,  while  its  lower  surface  rests  upon  the  convexity  of  the  eyeball. 
Consequently,  its  secretion  is  poured  into  the  outer  and  upper  recess 
of  the  conjunctival  sac,  whence  it  is  spread  by  capillarity  across  the 
cornea,  moistening  its  surface  as  well  as  that  of  the  opposing  conjunc- 

1  Noll,  Archiv  fur  mikr.  Anatomie,  Iviii,  1901,  also:  Dobrenil,  Dissertation, 
Lyons,  1907. 

-  Dogiel,  Archiv  f  iir  mikr.  Anatomie,  xliv,  1895. 


808 


THE    SENSE    OF    SIGHT 


tiva.  Eventually  it  is  collected  in  the  lacrimal  lake,  a  bay-like  ex- 
pansion at  the  inner  angle  of  the  eye  overlying  the  pHca  semilunaris 
and  the  spongy  reddish  elevation,  known  as  the  caruncula  lacrymalis.^ 
We  observe  here  that  each  lid  is  slightly  raised  into  a  papilla,  the 


Fig.  421. — Diagrammatic  Representation  of  Alveoli  of  the  Lacrimal  Cjland. 
A,  during  rest;  B,  after  activity  produced  by  pilocarpin. 

apex  of  which  displays  the  orifice  (punctum)  of  a  small  canal,  known 
as  the  canaliculus  lacrymalis.  The  purpose  of  these  tubules  is  to 
convey  the  tears  out  of  the  conjunctival  sac  into  the  lacrimal  sac, 
representing  the  slightly   dilated   orbital  end  of  the  lacrimal  duct. 


^OE^-- 


Iftmj' joaXpcbrcJ. 
ICqcotTV&nt 


ConchcL. 
Inferior 


Fig.  422. — Section  Showing  the  Cotjhse  and  Relations  of  the  Nasal  Sac  and  Duct. 
(Slighily  modified  from  Mcrkel.) 

The  latter  is  about  5  mm.  wide  and  15  mm.  long,  and  continues  on- 
ward in  the  form  of  the  nasal  duct  which  finally  terminates  in  the 
fore-part  of  the  lower  meatus  of  the  nose  about  30  to  35  mm.  behind 
the  posterior  margin  of  the  anterior  nasal  opening  (Fig.  422). 
1  Stieda,  Archiv  fiir  mikr.  Anatomie,  xxxvi,  1890. 


THE    CORNEA,    IRIS    AND    AQUEOUS    HUMOR  809 

These  channels  are  lined  with  columnar  (jpilhelium  which  l)(!Conies 
ciliated  in  places.  'r!u>ir  walls  are  stn^ngtlu^ned  by  muscle  tissue;  which 
on  contraction  lends  to  enlarge  their  lumen.  This  is  especially  true 
of  Horner's  muscle  which  (Mivelops  tlu>  posterior  wall  of  th(!  lacrimal 
sac  and  which,  during  the  closure  of  the  lids,  widcnis  this  passage  and 
aspirates  the  tears  through  the  dilated  punctum.  ('onversely,  the 
opening  of  the  lids  tends  to  compress  the  lacrimal  sac  so  that  its  con- 
tents are  forced  onward  into  the  nasal  duct.^  At  this  time  the 
sphincter-like  punctum  is  c1os(hI,  while  the  valve  of  Hasncr  guarding 
the  orifice  of  the  nasal  duct,  is  opened.  It  should  also  be  mentioned 
that  the  tears  are  ordinarily  prevented  from  escaping  across  the  edges 
of  the  eyelids  by  the  oily  deposits  furnished  by  the  Meibomian  glands. 
The  latter  are  sebaceous  in  character  and  are  arranged  in  rows  along  the 
inner  margin  of  each  lid.  The  tears  themselves  are  alkaline  in  reaction 
and  are  chiefly  composed  of  water  (98.1  per  cent.).  They  contain 
albumin  (0.1  per  cent.)  mucin,  epithelial  cells  (0.1  per  cent.)  and  salts, 
principally  sodium  chlorid  (0.4  to  0.8  per  cent.). 


CHAPTER  LXIX 
THE  CORNEA,  IRIS  AND  AQUEOUS  HUMOR 

The  Refractive  Power  of  the  Cornea. — The  cornea  of  the  mam- 
malian eye  is  a  perfectly  stationary  structure  possessing  a  certain 
curvature  and  refractive  power.  In  the  birds,  on  the  other  hand,  it  is 
set  in  a  cartilaginous  ring  and  its  convexity  may  be  altered  by  muscular 
activity.  This  fact  indicates  that  in  these  animals  it  is  made  to  serve 
as  a  powerful  adjunct  to  the  lens  and  thus,  is  in  large  part  responsible 
for  the  keen  sense  of  vision  possessed  by  them.  In  the  higher  mam- 
mals, its  importance  is  relatively  slight,  because  its  radius  of  curvature 
is  only  7.8  mm.,^  but  this  measurement  pertains  only  to  its  central 
area  situated  directly  in  front  of  the  pupil.  Its  marginal  zone  is  of 
practically  no  optical  importance  even  when  the  pupillar  orifice  is 
enlarged.  It  may  be  concluded,  therefore,  that  the  cornea,  by  virtue 
of  its  convexity,  renders  the  entering  rays  of  light  slightly  more  con- 
vergent. In  addition,  it  collects  many  of  the  otherwise  too  divergent 
rays,  and  directs  them  through  the  pupillar  opening  so  that  they  may 
still  be  subjected  to  the  refraction  of  the  lens. 

The  Aqueous  Humor. — It  has  been  stated  above  that  the  anterior 
cavity  of  the  eyeball  consists  of  the  anterior  and  posterior  chambers, 
the  former  being  situated  in  front  of  the  iris  and  the  latter,  between 
the  posterior  surface  of  this  partition  and  the  anterior  aspect  of  the 

1  Scimeni,  Archiv  flir  Physiol.,  1892,  Suppl.  291. 

2  Helmholtz,  Physiolog.  Optik,  Berlin,  1896. 


810  THE    SENSE    OF    SIGHT 

lens  and  ciliary  body.  Many  physiologists,  however,  believe  that  in 
adult  life  the  iris  lies  in  absolute  contact  with  the  lens  and  that  the  pos- 
terior chamber  is  merely  a  potential  space.  The  transparent  liquid 
filling  this  entire  cavity,  is  known  as  the  aqueous  humor.  Its  quantity 
amounts  to  about  0.4  c.mm.  and  its  specific  gravity  to  1.0053-1.008, 
which  is  the  equivalent  of  a  solution  of  sodium  chlorid  of  a  concen- 
tration of  rather  more  than  1.0  per  cent.^  Its  osmotic  pressure 
is  somewhat  higher  than  that  of  the  serum  of  the  blood.  ^  It  may  con- 
tain a  few  leukocytes,  but  only  0.08-0.12  per  cent,  of  protein.  This 
watery  fluid  also  permeates  the  interstitial  spaces  of  the  gelatinous 
substance  of  the  vitreous  humor. 

If  a  small  manometer  is  connected  with  the  anterior  chamber  of  the  eye  by- 
means  of  a  tubular  needle,  it  will  be  noted  that  the  aqueous  humor  is  held  under  a 
pressure  of  about  25  mm.  Hg.  This  pressure  is  designated  as  the  intraocular 
■pressure.  Its  very  obvious  function  is  to  render  the  eyeball  tense  so  that  its  differ- 
ent refractive  elements  are  fully  unfolded.  It  need  scarcely  be  emphasized  that 
any  unevenness  in  the  cornea  or  an  unduly  relaxed  ciliary  body  and  ligament  must 
greatly  impair  the  usefulness  of  these  structures  for  refraction.  In  addition,  it 
may  justly  be  assumed  that  the  aqueous  humor  forms  the  nutritive  medium  for 
the  lens,  ciliary  ligaments,  and  vitreous  humor,  because  these  structures  are  not 
directly  supplied  with  blood.  In  certain  pathological  conditions,  such  as  glaucoma, 
the  intraocular  pressure  is  enormously  increased  so  that  the  eyeball  can  scarcely 
be  indented  with  the  finger.  Clinically  the  tenseness  of  the  eyeball  is  measured  by 
means  of  the  ophthalmotonometer.  This  instrument  is  pressed  against  the  outer 
surface  of  the  eyeball  until  its  plate-like  extremity  causes  a  certain  flattening  at  the 
point  of  contact.  The  pressure  necessary  to  accomplish  this  end,  is  indicated  by 
a  tension  spring. 

A  number  of  observations  have  been  made  which  prove  conclusively 
that  the  aqueous  humor  is  continually  renewed.  Thus,  any  operation 
requiring  an  incision  through  the  cornea,  most  generally  leads  to  a  loss 
of  a  considerable  portion  of  this  fluid  which  is  again  reformed  in  the 
course  of  a  few  days.  Furthermore,  it  is  possible  to  drain  it  off  in  a 
relatively  steady  stream  by  inserting  a  dehcate  cannula  through  the 
margin  of  the  cornea.  Its  character  is  then  gradually  changed  until 
it  contains  as  much  as  3  or  4  per  cent,  of  proteins  and  becomes  coagula- 
ble.  It  is  commonly  held  that  the  aqueous  humor  is  secreted  by 
the  epitheUum  of  the  ciliary  body  and  its  glands.  From  here  it  flows 
into  the  anterior  recess  of  the  posterior  (vitreous)  cavity  of  the 
eyeball,  whence  it  finds  its  way  through  the  clefts  in  the  ligamentum 
pectinatum  iridis  into  the  angle  of  the  anterior  chamber.  A  portion 
of  this  fluid  also  escapes  through  the  meshes  of  the  ciliary  ligament  into 
the  posterior  chamber  situated  between  the  iris  and  the  lens,  and  thence 
round  the  edge  of  the  iris  into  the  anterior  chamber.  The  canal  of 
Schlemm  is  the  natural  drainage  tube  of  this  space.  A  portion  of  this 
fluid  also  escapes  into  the  Ijmiph  spaces  of  the  iris  and  from  here  into 
the  perichoroideal  lymphatics.  Still  another  portion  is  diverted  from 
the  ciliary  glands  into  the  interstitial  spaces  of  the  vitreous  humor, 

1  Golowin,  Archiv  fiir  Ophthalm.,  li,  1900. 

2  Hamburger,  Osmotischer  Druck  and  Jonenlehre,  1904. 


THE    CORNEA,    IRIS   AND    AQUEOUS    HUMOR  Sll 

whence  it  finds  its  way  into  the  lymphatics  accompanying  the  optic 
nerve. 

At  all  events,  the  offlow  balances  the  production,  so  that  the  aque- 
ous and  vitreous  iuunors  iwe,  constantly  held  under  a  pressure  of  about 
25  mm.  Hg.  This  imiilies  that  these  dilTcrcnt  drainage;  tuljes  are 
adjusted  so  as  to  place  a  considerabh;  resistance  in  the  path  of  the 
escaping  fluid.  In  spite  of  this  fact,  however,  it  has  been  estimated 
that  at  least  6  c.mm.  of  new  secretion  are  required  per  minute  in  order 
to  maintain  the  pressure  at  the  height  just  stated;  moreover,  it  has 
been  found  that  its  (quantity  may  be  varied  considerably  by  either 
raising  or  lowering  the  blood  pressure.  It  cannot  be  doubted  that 
this  factor  plays  an  important  part  in  all  processes  of  secretion,  because 
it  gives  rise  to  the  secretory  pressure,  but  it  seems  that  it  is  of  special 
value  for  the  formation  of  the  aqueous  humor.  This  fact  suggests 
that  this  fluid  finds  its  origin  in  large  part  in  transudation. 

The  Iris.^The  circumferential  border  of  the  iris  is  anchored  to  the 
eyeball  immediately  in  front  of  the  ciliary  body.  At  this  point  it  is 
continuous  with  the  choroid  coat  as  well  as  with  the  cornea  through 
the  ligamentum  pectinatum.  In  its  course  through  the  aqueous 
chamber,  its  posterior  surface  is  brought  into  close  relation  with  the 
ciliary  body  and  lens,  while  its  anterior  surface  is  everywhere  fully 
exposed  to  the  humor  filUng  this  cavity.  Its  inner  margin  surrounds 
an  orifice,  the  pupil,  through  which  the  rays  of  light  are  enabled  to 
enter  the  vitreous  chamber.  This  orifice  is  nearly  circular  in  shape 
and  is  placed  somewhat  nearer  the  nasal  side  of  the  eyeball.  Under 
ordinary  conditions  its  diameter  measures  about  4  mm.,  but  is  subject 
to  constant  changes  in  consequence  of  variations  in  the  intensity  of  the 
light  and  the  range  of  accommodation.  A  fuller  discussion  of  this 
phenomenon  will  be  given  in  a  subsequent  paragraph. 

When  looked  at  from  in  front,  the  iris  measures  about  11  mm.  across^ 
its  inner  margin  being  held  at  a  distance  of  about  5  mm.  from  its  cir- 
cumference. Its  thickness  amounts  to  about  0.4  mm.  Its  body  is 
formed  by  a  stroma,  consisting  of  a  delicate  framework  of  connective 
tissue,  the  fibers  of  which  are  in  large  part  arranged  in  a  radial  direc- 
tion. Anteriorly,  the  latter  is  lined  with  cells  similar  in  structure  to 
those  covering  the  posterior  limiting  membrane  (Descemet)  of  the 
cornea.  Posteriorly,  it  is  enveloped  by  two  layers  of  epithelial  cells, 
containing  black  pigment  to  which  the  blue  color  of  the  iris  is  due — blue 
because  transmitted  through  the  stroma.  Its  different  shades  of 
black,  brown  and  gray,  however,  are  caused  bj^  pigment  cells  which  are 
scattered  through  the  substance  of  the  stroma.^ 

The  plain  muscle  fibers  of  the  iris  are  arranged  either  circularly 
around  the  lumen  of  the  pupil  or  radially  to  it.  The  former  are  most 
numerous  right  next  to  its  margin,  where  they  form  a  conspicuous 
sphincter,  about  0.5  mm.  in  width.     The  latter  form  a  layer  of  elon- 

1  Retzius,  Biolog.  Untersuchungen,  1893. 


812  THE    SENSE    OF    SIGHT 

gated,  spindle-shaped  cells  close  to  the  pigment  layer.  ^  The  blood- 
supply  of  the  iris  is  derived  from  the  long  and  anterior  ciliary  arteries, 
and  its  nejve  supply  from  the  long  and  short  ciliary  nerves.  The 
origin  and  function  of  these  nerves  will  be  more  fully  described  in  a 
later  paragraph. 

The  Function  of  the  Iris. — The  action  of  the  iris  may  be  compared 
to  that  of  the  adjustable  diaphragm  of  an  ordinary  photographic 
camera.     As  such  it  possesses  two  functions,  namely,  to: 

(a)  Vary  to  size  of  the  bundle  of  light  entering  the  vitreous  cavity,  (1)  during  far 
and  near  vision  or  accommodation,  and  (2)  during  the  alterations  in  the  intensity 
of  the  light. 

(6)  Direct  the  rays  of  light  through  the  center  of  the  lens  which  is  its  most  per- 
fectly refracting  part.  Thus,  by  excluding  the  margins  of  lens,  it  prevents  the 
occurrence  of  spherical  and  chromatic  aberration. 

It  should  be  evident  from  the  preceding  discussion  pertaining  to 
the  structure  of  the  iris,  that  the  contraction  of  its  circular  muscle 
fibers  decreases  the  size  of  the  pupil,  while  the  contraction  of  its  radial 
fibers  increases  it.  Thus,  we  find  at  times  that  the  margin  of  the 
iris  is  drawn  almost  completely  over  the  lens,  lessening  the  diameter 
of  the  pupil  to  less  than  1  mm.,  and,  at  other  times,  that  it  is  pulled 
outward  until  this  aperture  measures  as  much  as  8  mm.  across.  •  The 
former  change  constitutes  pupillar  constriction,  and  the  latter,  pupillar 
dilatation.  Obviously,  these  changes  either  diminish  or  increase  the 
number  of  the  light  rays  entering  the  vitreous  chamber.  A  diminution 
in  their  number  is  made  necessary  (o)  when  the  intensity  of  the  light 
is  great,  and  (b)  when  the  eye  is  adjusted  for  a  near  object.  Con- 
versely, an  increase  in  their  number  is  required  (a)  in  low  intensities  of 
light,  and  (b)  when  the  object  accommodated  for  is  situated  far  away 
from  the  eye.  Furthermore,  inasmuch  as  these  changes  are  effected 
as  a  result  of  reflex  stimulation,  we  commonly  speak  of  them  as  the 
light  and  accommodation  reflexes. 

The  Light  Reflex. — If  a  person  is  made  to  look  alternately  from  a 
partially  darkened  surface  into  a  light  of  moderate  intensity,  it  will 
be  observed  that  the  pupil  becomes  small  whenever  the  eye  is  more 
fully  illuminated.  An  intense  light,  in  fact,  decre  ses  its  size  to  almost 
that  of  the  point  of  a  pin.  It  is  true,  however,  that  this  change  in.  the 
illumination  must  be  effected  rather  rapidly,  otherwise  a  decided 
alteration  in  the  size  of  the  pupil  will  not  be  produced. ^  Moreover, 
if  the  constriction  has  been  continued  for  a  longer  time  than  3  or  4 
minutes,  its  size  gradually  increases,  owing  to  an  adaptation  and 
fatigue  of  the  constrictor  mechanism.  Ob\'iously,  the  purpose  of  an 
enlarged  pupil  is  to  augment  the  receptive  power  of  the  retina  by 
permitting  as  many  rays  as  possible  to  strike  it,  while  a  constricted 
pupil  serves  to  protect  the  retinal  elements  against  an  undue  and  in- 
jurious degree  of  stimulation. 

1  Grumert,  Arch,  fiir  Augenheilkunde,  xxxvi,  1898. 

2  Garten,  Pfhiger's  Archiv,  Ixviii,  1897,  68. 


THE    CORNEA,    IRIS    AND    AQUEOUS    HUMOR  813 

In  the  case  of  the  lip;hl  i(>flex,  the  sfiinuli  urc  received  upon  (he 
retina,  whence  they  ai-(>  conveyed  over  tlie  perijjlieral  optic  tract  to 
the  seconchiry  or  reflex  optic  center,  situatecl  in  the  anterior  corjxjra 
quadrigeniina  next  to  tlie  a(iue(Uict  of  Sylvius. ^  To  effect  pupillar 
constriction  they  are  transferred  from  here  to  the  oculomotor  nerve 
and  the  cihary  j2;an}j;H()n  and  nerves.  ]^u[)illar  (hlatation,  on  the  other 
hand,  is  accomphshed  with  the  aid  of  tlie  autonomic  fihers  and  lience, 
these  impulses  must  be  diverted  from  the  secondary  optic  center  into 
the  sympathetic  system  proper.  Some  authors  also  hold  that  the 
retina  gives  rise  to  two  kinds  of  fibers,  one  group  of  which  has  to  do 
with  visual  sensations  proper  and  the  other  solely  M'itli  the  differences 
in  the  intensity  of  the  light.^  The  time  which  is  required  for  this 
reflex  response  of  the  iris,  has  been  estimated  at  0.04  to  0.05  second. 

In  man,  as  well  as  in  those  animals  in  which  the  optic  fibers  decus- 
sate in  part,  the  light  reflex  is  bilateral,  so  that  light  falling  into  one 
eye  also  gives  rise  to  a  diminution  in  the  size  of  the  pupil  of  the  oppo- 
site organ.  This  is  not  the  case  in  such  animals  as  the  horse,  owl  and 
rabbit,  in  which  the  crossing  is  complete.^  Furthermore,  it  has  been 
noted  that  the  substance  of  the  iris,  and  especially  in  the  lower  forms, 
is  extremely  sensitive  to  light.  Even  small  pieces  of  the  iris  of  the  frog 
or  eel  may  be  made  to  contract  by  simply  permitting  a  beam  of  light  to 
fall  upon  them.^  Clinically,  the  power  of  reaction  of  the  pupils  is 
usually  tested  by  shading  one  eye  in  such  a  manner  that  its  pupillar 
orifice  can  be  observed  beneath  the  cover.  If  the  shaded  eye  is  then 
uncovered,  its  pupil  will  be  seen  to  constrict.  The  other  eye  also 
responds  but  not  so  intensely.  This  implies  that  the  direct  reaction 
to  light  is  usually  more  profound  than  the  consensual,  as  practised  in 
this  test. 

From  this  discussion  it  may  be  gathered  that  the  light  reflex  is 
abolished  whenever  the  aforesaid  reflex  arc  is  broken  at  any  point  of 
its  course.  This  calls  to  our  minds  the  important  fact  that  it  is  absent 
in  tabes  dorsalis  (locomotor  ataxia)  and  general  paresis,  while  the 
accommodation  reflex  is  preserved.  This  phenomenon  is  knowm  as  the 
Argyll-Robertson  sign.  Its  explanation  is  not  difficult  if  it  is  remem- 
bered that  the  nervous  paths  required  for  these  two  reflexes  are  totally 
different.  Thus,  the  afferent  arc  in  the  case  of  the  light  reflex  is 
formed  by  the  optic  nerve,  whereas  that  concerned  with  the  accomoda- 
tion reflex  is  formed  by  the  afferent  fibers  from  the  muscles  of  the  eye. 
Inasmuch  as  the  disease  of  tabes  dorsalis  is  characterized  by  a  pro- 
gressive degeneration  of  the  different  spinal  roots  and  tracts,  it  cannot 
surprise  us  to  find  that  similar  changes  are  finally  induced  in  the  optic 
path,  thereby  gradually  blocking  the  impulses  from  the  retina.     At 

1  Hass,  Archiv  fiir  Augenheilkunde,  Ix,  1908,  327. 

2  Behr,  Archiv  fiir  Ophthalmologie,  Ixxxvi,  1913,  468. 
2  Steinach,  Pfliiger's  Archiv,  xlvii,  1890,  313. 

*  Arnold,  Physiologic,  ii,  1847;  also  see:  Steinach,  Pfliiger's  Archiv,  lii,  1892, 
495. 


814  THE    SENSE    OF    SIGHT 

this  time,  the  afferent  paths  having  to  do  with  the  accommodation 
reflex,  are  still  free  from  these  degenerative  alterations. 

The  Accommodation  Reflex. — If  a  person  is  asked  to  accommodate 
alternately  for  near  and  far  objects,  it  will  be  noted  that  the  size  of 
his  pupil  is  decreased  on  near  vision  and  increased  on  far  vision.  In 
the  former  instance,  the  number  of  raj's  entering  the  eye  is  diminished, 
but  not  at  all  sufl&ciently  to  impair  our  power  of  being  able  to  make 
out  the  finer  details  of  the  object.  This  reduction  in  the  size  of  the 
beam  of  hght  is,  of  course,  entirely  in  keeping  with  perfect  refraction, 
because  the  amount  of  light  projected  into  the  eye  from  any  given  ob- 
ject, increases  inversely  as  the  scjuare  of  its  distance.  This  implies 
that  the  phenomenon,  constituting  the  accommodation  reflex,  is  an 
associated  action  and  is  closely  interlinked  with  the  muscular  efforts 
necessar\'  for  accommodation.  These  efforts  consist  in  a  convergence 
of  the  ej'ebaUs  effected  by  the  contraction  of  the  two  internal  recti 
muscles,  and  a  contraction  of  the  cihaiy  muscles,  rendering  the  lens 
more  convex.  The  afferent  impulses  which  give  rise  to  these  reactions, 
are,  of  course,  chiefly  intracerebral  in  their  origin,  and  do  not  involve 
the  optic  tract.  Consequently,  it  appears  that  the  constriction  of  the 
pupil  on  near  vision  is  due  to  the  fact  that  those  motor  discharges 
from  the  midbrain  which  evoke  the  contraction  of  the  internal  recti 
and  ciUary  muscles,  overflow  and  simultaneously  activate  the  neigh- 
boring center  for  the  sphincter  fibers  of  the  iris. 

In  sleep  the  pupils  are  constricted  in  spite  of  the  fact  that  the  eyes 
are  not  stimulated  by  light.  This  fact  may  seem  to  be  opposed  to 
the  view  just  expressed,  unless  it  is  remembered  that  the  axes  of  the 
eyeballs  are  at  this  time  turned  inward  and  upward.  Obviously, 
therefore,  the  initial  constriction  of  the  pupil  during  sleep  is  an  associ- 
ated movement,  akin  to  that  arising  on  near  vision;  in  other  words,  the 
motor  impulses  which  are  required  to  deviate  the  eyeballs  in  the  afore- 
said direction,  also  implicate  the  sphincter  muscle  of  the  iris. 

The  constriction  of  the  pupil  during  the  initial  stage  of  anesthesia 
by  ether  or  chloroform  ma^'  be  explained  in  a  veiy  similar  way,  because 
these  agents  give  rise  at  first  to  a  general  excitation  of  the  central  ner- 
vous system.  As  soon  as  this  primary'  effect  has  weakened,  the  pupil 
retains  an  intermediate  size,  but  dilates  immediately  if  the  narcosis 
is  deepened  or  is  carried  beyond  its  physiological  hmit.  This  danger 
point  of  narcosis  maj'  also  be  determined  in  other  waj's,  for  example, 
by  noting  the  intensity  of  the  reflexes  and  especially  of  those  which  are 
usually  preserved  during  sleep  and  moderate  narcosis.  The  one  most 
commonly  employed  for  this  purpose  is  the  corneal,  consisting  in  a 
closure  of  the  eyehds  upon  mechanical  stimulation  of  the  cornea. 
Among  the  agents  which  constrict  the  pupil,  may  be  mentioned 
opium,  and  its  alkaloid  morphin,  as  well  as  the  alkaloids  eserin  or 
physostigmin  and  pilocarpin.  Among  the  dilators  of  the  pupil 
should  be  cited  the  alkaloids  of  belladonna,  namely,  atropin  and  homa- 
tropin.     A  dilatation  of  the  pupil  commonly  results  in  consequence 


THE    CORNEA,    IRIS    AND    AQUEOUS    HUMOR  815 

of  depressions  of  the  nervous  centers,  as  well  as  in  all  conditions  of  ner- 
vous exhaustion,  deep  narcosis  and  comas.  In  dyspnea  the  pupils  are 
large,  but  b(H'onie  smaller  if  this  condition  is  changed  into  asphyxia. 
They  are  also  enlarged  by  sc^nsoiy  impulses  from  the  digestive  and 
sexual  organs,  as  well  as  by  somatic  and  visceral  sensations  of  pain. 
Even  the  cerebral  cortex  may  influence  their  size  without  any  apparent 
peripheral  stimulation.  Thus,  it  has  been  shown  by  Haab  that  if  a 
person  is  made  to  look  at  a  dark  wall,  while  his  eyes  are  illuminated 
by  a  constant  light  placed  laterally  in  front  of  him,  a  marked  constric- 
tion of  his  pupils  results  whenever  his  attention  is  called  to  the  light. 
Quite  similarly,  his  pupils  may  be  made  to  dilate  at  any  time  by 
drawing  his  attention  to  the  dark  wall.  Some  persons,  indeed,  are 
able  to  constrict  and  to  dilate 
their  pupils  by  merely  calling  up 
a  mental  picture  of  bright  and 
dark  objects. 

Spherical  Aberration. — In  dis- 
cussing the  focal  points  formed 
by  spherical  lenses,  we  have  as- 
sumed that  the  rays  emitted  by  a 
luminous  object  are  sharply  inter- 
sected behind  the  lens.  Strictly 
speaking,  this  is  not  true,  because 
the    refraction    of   a   lens   differs 

somewhat  in  its  different  zones  for  ^^^    423.-Diagram  Illustrating 

the  reason  that  its  prismatic  con-  Spherical  Aberration. 

Stituents    are    not    centered    with  The  iris  being  retracted  the  rays  of  light 

sufficient   accuracy   to   act  in  per-    P^^^  through  the  outer  zone  of  the  lens  and 
rj-,,  c  \li       ^^®  more  sharply  retracted  than  those  tra- 

fect   unison.      The   most  perfectly    versing  its  center. 

refracting  portion  of  a  lens  is  its 

central  area,  having  an  aperture  not  exceeding  10°  to  12°.  If  the  size 
of  this  aperture  is  increased  so  that  the  rays  can  also  traverse  its 
peripheral  segments,  these  rays  will  be  brought  to  a  focus  in  front  of  the 
focal  point  of  those  refracted  through  its  center  (Fig.  423).  The  in- 
tersections of  these  aberrated  rays  are  called  caustics.  Obviously, 
their  presence  must  render  the  image  indistinct.  This  condition  which 
is  called  spherical  aberration,  is  also  present  in  the  lens  of  our  eye,  but 
is  prevented  from  interfering  with  the  formation  of  the  retinal  image 
by  the  fact  that  its  peripheral  extent  is  usually  covered  by  the  margin 
of  the  iris.  In  this  regard,  therefore,  the  latter  performs  the  func- 
tion of  a  stop,  i.e.,  it  cuts  off  the  rays  from  the  circumference  of  the 
lens  and  allows  only  the  passage  of  a  concentrated  central  beam. 

Chromatic  Aberration. — If  a  bundle  of  light  is  projected  through  a 
lens,  it  will  be  noted  that  the  rays  traversing  its  central  segment  appear 
on  its  other  side  chiefly  as  white  light,  while  those  passing  through  its 
peripheral  zone  are  dispersed  into  their  different  colored  components. 
The  image  then  appears  surrounded  by  a  colored  margin.     This  effect 


816  THE    SENSE    OF    SIGHT 

is  to  be  expected,  since  light  in  passing  from  a  rare  into  a  dense  medium 
suffers  a  retardation,  and  this  diminution  in  its  velocity  affects  its 
component  rays  differently,  i.e.,  those  at  the  red  end,  with  long  wave- 
lengths, are  refracted  the  least  and  those  at  the  violet  end,  with  short 
wave-lengths,  the  most.  Inasmuch  as  a  lens  is  composed  of  a  series 
of  prisms — and  prisms  split  the  white  light  in  accordance  with  the 
unequal  refrangibility  of  its  simple  color  components — a  spectrum  must 
result  (Fig.  424).  Thus,  white  light,  when  passed  through  the  edge 
of  a  biconvex  lens,  is  dispersed  so  that  its  violet  rays  are  brought 
to  a  focus  (7)  in  front  of  its  red  rays  {R),  while  the  foci  of  its  orange, 
yellow,  green,  blue  and  indigo  are  situated  in  between  these  two  ex- 
tremes. This  condition  which  is  called  chromatic  aberration,  is  also 
present  in  the  lens  of  our  eye,  but  cannot  seriously  interfere  with  the 
formation  of  the  image,  because  the  iris  does  not  permit  the  rays  of 


Fig.  424. — Diagram  Illustpiating  Chromatic  Aberration. 
The  iris  being  retracted,  the  rays  of  white  light  traversing  the  peripheral   zones  of 
the  lens  are  split  into  their  spectral  components.     The  violet  rays  are  focalized   nearer 
the  lens  than  the  red.  ^ 

light  to  pass  through  its  more  poorly  refracting  peripheral  portion. 
By  analogy,  it  may  be  concluded  that  the  mydriatic  eye  receives  chro- 
matically aberrated  images,  because  the  edge  of  its  lens  is  fully  exposed 
to  the  entering  beam  of  light.  In  artificial  lenses  this  difficulty  is 
often  overcome  by  combining  crown  glass  with  flint  glass.  Inasmuch 
as  the  dispersive  power  of  these  glasses  is  very  different,  their  individual 
dispersion  may  thereby  be  corrected  without  considerably  lessening 
their  total  refractive  power.  This  principle  has  been  made  use  of  by 
Dolland  in  the  construction  of  the  achromatic  lenses,  achromatism 
being  the  term  applied  to  the  phenomenon  of  the  refraction  of  light 
without  decomposition  into  its  components. 

It  is  a  well-known  fact  that  if  we  gaze  at  a  red  and  violet  light 
placed  at  the  same  distance  in  front  of  us,  the  former  appears  to  be 
the  more  prominent  and  seems  nearer  to  us.  Clearly,  this  is  merely 
an  error  of  judgment,  because  since  the  red  rays  possess  a  greater 


THE    CORNEA,    IRIS    AND    AQUEOUS    HUMOR  817 

wavo-longth,  a  greator  effort  at  accoiuinodalion  is  rociuiretl  in  order- 
to  bring  them  to  a  precise  foeal  point  upon  our  retina. 

Miosis  and  Mydriasis. — These  terms  are  commonly  employed  to 
indicate  that  the  size  of  tiu^  pupil  has  been  varied  })y  means  of  drugs  or 
in  consequence  of  pathological  lesions.  Miosis  signifies  pupillar  con- 
striction, and  mydriasis,  pui)illar  dilatation.  The  first  condition  is 
commonlj^  associated  with  congestion  and  traumas  of  the  iris,  certain 
fevers,  pulmonary  congestion,  and  lesions  of  the  sympathetic  system. 
Among  the  miotics  might  be  mentioned  physostigmin  feserin), 
muscarin,  and  pilocarpin.  Their  action  appears  to  be  due  to  their 
power  of  stimulating  the  nerve  fibers  and  corresponding  receptor 
substance  of  the  constrictor  muscle.  The  mydriatics  commonly  made 
use  of,  are  atropin,  homatropin  and  cocain.  The  first  two  act  by 
paralyzing  the  endings  or  receptor  substance  of  the  constrictor  nerve 
fibers.^  Cocain  exerts  a  similar  action,  but  only  in  larger  doses,  while 
in  smaller  doses,  it  stimulates  the  dilator  mechanism.  Mydriasis  is 
also  obtained  in  glaucoma,  atrophy  of  the  optic  nerve  and  orbital 
diseases. 

A  mydriatic  eye  must,  of  course,  be  shielded  against  light,  because 
it  is  temporarily  unable  to  protect  itself.  In  addition,  it  should  be 
remembered  that  the  mydriatics  temporarily  destroy  the  mechanism 
of  accommodation,  because  they  paralyze  the  ciliary  muscle  which  is 
similarly  innervated.  Near  vision,  therefore,  is  practically  impossible 
at  this  time.  The  miotics,  on  the  other  hand,  also  stimulate  the  ciliary 
muscle  and  keep  the  eye  in  a  condition  of  forced  accommodation.  In 
the  latter  case,  therefore,  far  vision  is  practically  impossible. 

The  Innervation  of  the  Iris. — The  circular  and  radial  fibers  of  the 
iris  receive  their  nerve  supply  from  the  autonomic  system,  the  relay 
stations  nearest  them  being  the  ciliary  ganglion  and  the  superior  cervi- 
cal ganghon.  Preganglionically,  however,  these  fibers  find  their  origin 
in  the  cerebrospinal  system.  As  far  as  the  sphincter  iridis  is  con- 
cerned, it  may  be  shown  that  its  nerve  fibers  arise  in  the  midbrain  in 
the  anterior  part  of  the  nucleus  of  the  third  cranial  nerve.  They  make 
use  of  the  third  nerve  as  a  highway  to  reach  the  ciliary  ganglion,  whence 
they  continue  onward  postganglionically  in  the  short  ciliary  nerves. 
The  nerve  fibers  innervating  the  dilator  mechanism  of  the  iris,  sup- 
posedly the  radial  muscle  fibers,  also  arise  in  the  midbrain,  but  their 
place  of  origin  is  not  definitely  known.  From  here  they  descend  in 
the  spinal  cord,  but  leave  this  structure  in  the  eighth  cervical  and  the 
first  and  second  thoracic  spinal  nerves  to  enter  the  sympathetic  system 
by  way  of  the  rami  albi  communicantes.  They  then  ascend  to  the 
superior  cervical  ganglion  by  way  of  the  cervical  sympathetic  nerve 
and  finally  reach  the  Gasserian  ganglion.  Distally  to  this  point  they 
invade  the  ophthalmic  branch  of  the  fifth  cranial  nerve  and  its  long 
ciliary  branch. 

^Langley,  Jour,  of  Physiol.,  xxxix,  1909,  235. 

52 


818 


THE    SENSE    OF    SIGHT 


On  excitation  of  the  trunk  of  the  third  nerve,  we  obtain  a  constric- 
tion of  the  pupil,  while  the  stimulation  of  the  sympathetic  nerve  in 
its  cervical  portion,  gives  rise  to  pupillar  dilatation.  Obviously,  there- 
fore, the  division  of  the  former  must  evoke  a  dilatation  of  the  pupil, 
and  that  of  the  latter,  pupillar  constriction.  Under  normal  conditions, 
these  two  mechanisms  are  tonically  set  and  oppose  one  another.  Con- 
sequently, the  removal  of  the  constrictor  impulses  must  allow  the 
dilator  impulses  to  gain  the  upper  hand,  while  the  division  of  the  sym- 
pathetic nerve  must  permit  the  constrictor  influences  to  exert  their  full- 


FiG.  425. — Diagrammatic    Representation   of   the    Nerves    Governing    the    Pupil. 

(After  Foster.) 
II,  optie  nerve;  eg,  ciliary  ganglion;  rb,  its  short  root  from  ///,  motor  oculi    nerve; 
sym.,  its  sympathetic  root;  rl,  its  long  root  from  V,  ophthalmonasal  branch    of  oph- 
thalmic division  of  fifth  nerve;  sc,  short  ciliary  nerves;  le,  long  ciliary  nerves. 


est  power.  It  appears,  therefore,  that  the  constrictor  and  dilator 
muscles  of  the  iris  are  arranged  antagonistically  to  one  another,  in 
a  manner  similar  to  that  of  the  flexor  and  extensor  muscles  of  the  ex- 
tremities (Sherrington).  Thus,  inasmuch  as  it  has  been  shown  that 
the  contraction  of  one  set  of  skeletal  muscles  is  usually  facilitated  by 
the  inhibition  of  the  other  set,  it  may  be  assumed  that  a  similar  recipro- 
cal relationship  exists  between  the  muscle  fibers  of  the  iris.     Certain 


THE    CILIARY   BODY    AND    LENS 


819 


evidence  in  support  of  tliis  reciprocal  action  has  been  furnished  by 
Anderson.  ^ 

In  this  connection,  it  should  also  be  mentioned  that  the  oculomotor 
and  short  ciliary  nerves  innervate  the  ciliary  muscle  which  is  used  in 
accommodation.  For  this  reason,  the  excitation  of  this  nerve  really 
produces  a  double  effect,  i.e.,  it  constricts  the  pupil  and  also  renders 
the  lens  more  convex.     Concurrently,  its  division  must  be  followed  not 

Gasserian-        "^ — v.    Ojbht/ialmie  branch  of  St*'  Zona  ctliaru  nerues. 

Ganglion..  \        >- 1-  .^yj  \^DUaIor 


(Superior  CervieaL 


oJputal 
Cord 


joufriUojt. 


Ciliary 0an^lieru  Slwrl Ciliary  Tierves 


Fig.  426. — Schema  Showing  the  Path  of  the  Preganglionic  and  Postganglionic 
Fibers  to  the  Ciliary  Muscle  .\nd  to  the  Sphincter  and  Dilator  Muscles  of  the 
Iris.      {Modified  from  Schultz.) 

only  by  pupillar  dilatation  but  also  by  a  flattening  of  the  lens,  which 
change  renders  it  adapted  for  far  vision. 


CHAPTER  LXX 


THE  CILIARY  BODY  AND  LENS 

The  Ciliary  Body. — The  space  beween  the  ora  serrata  of  the 
retina  and  the  base  of  the  iris  is  occupied  by  the  ciliary  processes  of 
the  choroid,  its  muscles,  ligaments  and  glands.  In  this  region,  the 
choroid  is  considerably  thickened,  measuring  6  to  7  mm.  across.  In 
cross-section  it  displays  a  triangular  outline,  which  is  largely  taken  up 
by  strands  of  plain  muscle  tissue,  forming  the  cihary  muscle.  These 
fibers  are  arranged  in  two  ways,  namely,  longitudinallj^  and  transversely 
to  the  long  axis  of  the  eyeball.  The  former  arise  from  the  fore-part 
of  the  sclerotic  coat  close  to  the  cornea,  where  they  are  attached  to 
the  ligamentum  pectinatum.  They  pursue  a  course  almost  directly 
^  Jour,  of  Physiology,  xxx,  1903,  15. 


820  THE    SENSE    OF    SIGHT 

backward  to  be  inserted  in  the  choroid  at  and  behind  the  ciliary 
process.  The  circular  fibers  are  most  numerous  in  the  base  of  the 
ciliary  body,  and  pursue  a  course  circularly  around  the  aperture  in 
which  the  lens  is  suspended.  They  are  most  clearly  in  evidence  in 
hypermetropic  persons.  ^ 

The  aperture  between  the  margins  of  the  ciliary  body  is  occupied 
by  the  lens.  The  latter  is  invested  by  a  transparent  and  elastic 
capsule,  measuring  in  front  6.5  to  25 ju  in  thickness.  Its  substance 
is  composed  of  a  firm  central  and  softer  cortical  portion,  both  of  which 
appear  as  hexagonal,  prismatic  lamellae  of  homogeneous  elastic  tissue. 
A  single  layer  of  cuboidal  cells,  2.5  to  10m  in  height,  forms  their  outer 
investment.  It  is  to  be  noted  especially  that  the  edge  of  the  lens  is 
not  in  absolute  contact  with  the  margin  of  the  ciliary  body,  but  re- 
mains at  some  distance  from  it,  the  intervening  space  being  occupied 
by  ligamentous  bands  which  extend  straight  across  from  its  capsule  to 
the  surface  of  the  ciliary  body.  Furthermore,  these  ligamentous 
fibers  pursue  a  pecuhar  diagonal  course,  some  of  them  arising  upon 
the  posterior  aspect  of  the  ciliary  body  and  terminating  upon  the 
anterior  surface  of  the  lens,  while  others  arise  upon  the  anterior  surface 
of  the  cihary  body  and  end  upon  the  posterior  surface  of  the  lens.  We 
shall  have  occasion  to  refer  to  these  data  again  later  on,  while  dis- 
cussing the  accommodation  of  the  eye  for  near  objects. 

The  Process  of  Accommodation  in  Different  Animals. — The  pur- 
pose of  the  lens  is  to  bring  rays  of  light  to  a  precise  focus  upon  the 
retina.  In  this  function  it  is  aided  in  a  slight  measure  by  the  other 
refractive  media  of  the  eye.  But,  since  objects  are  situated  at  different 
distances  from  the  eye,  some  means  must  be  provided  by  which  their 
images  may  be  retained  upon  the  retina;  in  other  words,  the  eye  must 
be  able  to  accommodate  itself  to  these  varying  distances.  To  ap- 
proach this  subject  in  the  most  logical  way,  inquiry  should  first  be 
made  regarding  the  manner  in  which  the  ordinary  photographic  camera 
may  be  adjusted  for  far  and  near  objects.  Two  ways  are  open  to  us, 
namely,  to  move  the  sensitive  plate  either  nearer  to  or  farther  away 
from  the  lens,  or  to  move  the  latter  either  nearer  to  or  farther  away 
from  the  plate.  A  third  method  would  be  to  permit  the  screen  as  well 
as  the  lens  to  remain  stationary  and  to  adjust  the  focal  distance  of 
the  camera  by  interposing  other  lenses  of  different  refractive  power. 
This  procedure,  however,  is  not  in  common  use,  because  it  is  less 
convenient  than  the  other  two. 

In  the  animal  kingdom,  however,  the  third  method  is  imitated  by 
varying  the  convexity  of  the  lens,  while  its  position,  as  well  as  that  of 
the  retina,  remains  unchanged. 

Indeed,  the  mechanism  of  accommodation  is  so  diversified  among  the  different 
animals  that  really  all  of  the  physical  means  just  enumerated  find  their  prac- 
tical appUcation.2     To  begin  with,  it  should  be  noted  that  certain  species  lack 

1  Iwanoff,  Archiv  fiir  Ophthalmol.,  xv,  1869,  1. 

2  Beer,  Wiener  klin.  Wochenschr.,  1898,  No.  12. 


THE    CILIARY   BODY    AND    LENS 


821 


this  power  altogether,  while  others  possess  it  in  only  a  very  rudimentary  degree. 
This  is  true  of  the  frog,  alligator,  vipers  and  certain  rodents.  Inasmuch  as  these 
animals  are  chiefly  dependent  upon  near  vision  and  are  nocturnal  in  their  habits, 
their  accommoilation  is  never  subjected  to  wide  variations.  P'urthermore,  their 
associations  are  so  poorly  developed  that  there  is  really  no  necessity  for  their  being 
able  to  discern  the  exact  details  of  an  object,  as  long  as  they  can  perceive  its 
simplest  movements.     They  are  essentially  shadow-animals. 

In  the  cephalopod  molluscs,  such  as  sepia,  we  observe  that  the  thin  globe  of 
the  eye  is  strengthened  by  a  transverse  ring  of  cartilage,  immediately  adjoining  an 
exceptionally  delicate  ring  of  tissue  (Fig.  427).  The  anterior  wall  to  this  eye  con- 
tains bands  of  meridional  muscle  fibers  which  are  attached  to  the  cartilaginous  ring 
(C)  and  are  inserted  in  the  ciliary  body.  On  contraction  this  muscle  pulls  the  entire 
anterior  half  of  the  eye  backward,  in  this  way  bringing  the  lens  nearer  the  retina. 
Thismovementnecessitates,  of  course,  a  redistribution  of  the  intraocular  pressure 
which  is  made  possible  by  a  bulging  of  the  thinned  wall  of  the  eyeball  directly 
behind  the  cartilaginous  ring.  It  need  scarcely  be  mentioned  that  this  approxi- 
mation of  the  lens  to  the  retina  enables  this  animal  to  accommodate  for  far  objects. 


Fig.    427. — Diagram    II- 

liUSTRATING     THE     PROCESS    OF 

Accommodation  in  the   Eye 
OF  Sepi.\. 

The  anterior  half  of  the 
eyeball  is  drawn  toward  the 
cartilaginous  ring  C  on  far 
vision. 


Fig.  428. — Diagram  Illustrating 
Process  of  Accommodation  in  the 
Eye  of  the  Fish. 

C,  cornea;  L,  the  lens  is  pulled 
toward  the  retina  on  far  vision  by 
R,  the  muse,  retractor  lentis. 


The  eyes  of  the  amphibians  and  many  reptiles,  such  as  the  snakes,  are  normally 
adjusted  for  far  vision.  In  these  animals  accommodation  is  effected  by  increasing 
the  distance  between  the  lens  and  the  retina.  This  change  is  accomplLshed  in  this 
way:  As  the  ciliary  muscle  contracts,  it  pulls  the  sclerotic-corneal  junction  back- 
ward, thereb}^  increasing  the  pressure  in  the  vitreous  cavity.  In  consequence  of 
this  increase  in  pressure,  the  lens  is  pushed  forward  into  the  aqueous  cavity  and 
approaches  the  cornea.  An  equalization  of  the  pressure  in  this  chamber  is  made 
possible  by  a  displacement  of  the  aqueous  humor  into  its  lateral  angle  which  has 
just  been  enlarged  by  the  retraction  of  the  ciliary  body.  It  is  e\'ident  that  this 
removal  of  the  lens  from  the  retina  must  increase  the  posterior  focal  distance 
and  must  accommodate  the  eye  for  near  objects. 

The  eyes  of  the  fishes  are  normally  set  for  near  objects  (Fig.  428).  They  are 
not  in  possession  of  ciliary  processes  nor  of  ciliary  muscles,  and  their  almost  spher- 
ical lens  is  suspended  in  the  visual  axis  by  means  of  flat  bands  of  connective  tissue, 
forming  the  so-called  suspensory  ligament.  The  lower  and  inner  pole  of  the  lens 
gives  attachment  to  a  number  of  horizontal  strands  of  muscle  fibers  which  on 
contraction  pull  the  lens  backward,  thereby  diminishing  the  distance  between  it 
and  the  retina.  This  muscle,  known  as  the  retractor  lentis,  lessens  the  posterior 
focal  distance  of  these  eyes  and  accommodates  them  for  far  objects.     Consequently, 


822  THE    SENSE    OF    SIGHT 

the  fish's  eye  may  be  made  extremely  myopic  by  surrovmding  it  with  air,  while 
that  of  a  terrestrial  animal  may  be  rendered  hypermetropic  by  placing  it  in 
water. 

The  birds  are  noted  for  their  exceptionally  accurate  and  rapid  accommodation. 
Their  eyes  are  normally  set  for  distant  objects,  and  their  accommodation  for  near 
objects  is  made  possible  not  by  changing  the  position  of  the  lens,  but  by  increasing 
its  convexity  and  hence,  its  refractive  power.  The  lens  is  enabled  to  change 
its  shape  by  lessening  the  tension  under  which  it  is  ordinarily  held.  This  relaxation 
is  effected  by  pulling  the  sclerotic-corneal  junction  backward.  Inasmuch  as  the 
suspensory  ligament  of  the  lens  is  attached  to  this  area  of  the  eyeball,  this  retrac- 
tion must  relax  it,  thereby  permitting  the  lens  to  become  more  convex  on  account 
of  its  inherent  elastic  power.  A  special  muscle,  known  as  Crampton's  muscle, 
controls  this  retraction.  It  is  also  of  interest  to  note  that  the  fibers  composing  it, 
are  of  the  striated  variety  and  are,  therefore,  underamoredirect  and  exact  control 
of  the  higher  centers  than  the  ciliary  muscle  of  the  mammals.  This  structural 
peculiarity  accounts  for  the  rapidity  of  the  accommodation  in  birds  which  enables 
them  to  swoop  down  from  great  heights  to  catch  their  prey.  In  addition,  the  birds 
of  prey  possess  the  power  of  increasing  the  convexity  of  their  cornea.  A  special 
muscle  is  provided  for  this  purpose. 

The  Accommodation  of  the  Human  Eye. — It  has  been  shown  by 
Helmholtz  that  the  accommodation  of  the  mammahan  eye  is  effected 
by  an  alteration  in  the  convexity  of  the  lens,  chiefly  of  its  anterior 
part.  Naturally,  an  increase  in  its  convexity  gives  rise  to  an  increase 
in  its  refractive  power  and  hence,  to  an  accommodation  for  near  ob- 
jects. Two  theories  have  been  formed  in  explanation  of  this  phe- 
nomenon, namely: 

(a)  The  greater  curvature  of  the  lens  on  near  vision  is  due  to  the  fact  that  it  is 
subjected  to  a  greater  tension  by  the  components  of  the  zonula  Zinnii.i 

(b)  The  greater  convexity  of  the  lens  on  near  vision  is  caused  by  the  fact  that 
the  tension  under  which  it  is  ordinarily  held  is  diminished  at  this  time. 

The  second  view  is  the  one  commonly  accepted  to-day.  It  is 
usually  designated  as  the  detention  theory  of  Helmholtz. ^  It  is 
believed  that  the  contraction  of  the  ciliary  muscles  causes  the  ciliary 
body  and  adjoining  choroid  to  be  pulled  forward.  In  consequence 
of  this  displacement,  the  ciliary  ligaments  are  loosened,  permitting 
the  lens  to  bulge  forward.  Besides,  it  must  be  evident  from  figure 
429  that  this  forward  movement  of  B  must  give  rise  to  a  relaxation  es- 
pecially of  those  ligamentous  bands  which  extend  between  the  posterior 
surface  of  the  ciliary  body  {CB)  and  the  anterior  marginal  zone  of  the 
capsule  of  the  lens  (L).  As  a  result  of  this  detention  of  its  peripheral 
area,  the  mass  of  the  entire  lens  adjusts  itself  and  assumes  a  more  spher- 
ical shape.     Its  anteroposterior  diameter  is  increased  thereby. 

While  it  is  a  matter  of  common  observation  that  even  lenses  with 
fluid  contents  tend  to  assume  a  spherical  outline,^  it  is  to  be  noted  that 
the  lens  of  the  mammalian  eye  is  invested  by  an  elastic  capsule. 
It  is  this  investment  which  is  chiefly  responsible  for  the  aforesaid 

1  Schon,  Pfliiger's  Archiv,  lix,  1895,  427;  also:  Tscherning,  Optique  physiol- 
ogique,  Paris,  1897. 

2  Physiol.  Optik,  ii,  136. 

^  Schweigger,  Archiv  fiir  Augenheilkunde,  xxx,  1895,  276. 


THE    CILIARY    HODV    AND    LENS 


823 


changes  in  the  lens.  We  liave  seen  that  the  ciHaiy  muscle  is  made  up 
of  meridional  and  circular  fibers.  Even  a  casual  study  of  their  course 
must  show  that  the  former  are  the  principal  factors  concerned  in  this 
detention,  but  it  cannot  be  denied  that  the  circular  fibers  are  a  most 
important  adjunct,  because  they  fix  the  base  of  th(;  ciliary  body  so 
that  the  longitudinal  fibers  can  gain  a  firmer  hold  upon  this  structure 
and  pull  it  forward.  That  a  movement  of  this  kind  actually  takes  place 
has  been  proved  by  Henson  and  Volker.^  Fine  needles  were  inserted 
through  different  segments  of  the  equatorial  region  of  the  eyeball 
which,  on  stimulation  of  the  ciliary  body,  showed  movements  indica- 
tive of  a  forward  displacement  of  the  choroidea. 


Fig.  429. — Diagram  Illustrating  the  Process  of  Accommodation  in  the  Himan  Eye. 
C,  cornea;  L,  lens;  J,  iris;  CL,  ciliary  ligament;  CB,  ciliary  body;  Ch,  choroid;  R, 
retina;  S,  sclera.  On  near  vision  the  ciliary  muscle  contracts,  drawing  the  region  i? 
nearer  to  region  A.  The  tension  upon  the  ciliary  ligament  being  diminished  therebj-, 
the  lens  assumes  a  more  spherical  shape,  chiefly  in  the  direction  of  the  cornea.  This 
change  is  indicated  in  red. 


Proofs  of  Accommodation. — When  the  eye  is  at  rest,  it  is  accom- 
modated for  far  objects.  We  may  convince  ourselves  of  this  fact  by 
suddenly  opening  the  eyehds  after  they  have  been  held  shut  for  a  short 
time.  We  then  become  conscious  of  a  relaxed  vision,  i.e.,  of  an  accom- 
modation for  far  objects,  and  also  of  a  distinct  effort  to  direct  the  eyes 
to  a  near  object.  During  relaxed  vision,  the  suspensory  ligaments 
are  placed  under  a  certain  tension,  thereby  retaining  the  lens  in  a 
somewhat  flattened  condition.  This  may  be  proved  by  measuring 
the  anterior  curvature  of  the  lens  before  and  after  the  excision  of  the 
eye.  It  is  very  obvious  that  a  lens  freed  from  its  attachments,  pos- 
sesses a  more  spherical  outline  than  one  still  in  its  normal  position. 
The  increased  curvature  of  the  lens,  and  especially  that  of  its  an- 

1  Archiv  fiir  Ophthalm.,  xLx,  1873,  156. 


824  THE    SENSE    OF    SIGHT 

terior  portion,  leads  to  a  movement  of  this  surface  toward  the  cornea. 
This  change  may  be  studied  in  any  human  eye,  if  the  person  under 
observation  changes  his  accommodation  repeatedly  from  far  to  near 
objects.  The  most  obvious  alteration  consists  in  a  forward  displace- 
ment of  the  margin  of  the  iris,  caused  by  the  forward  bulging  of  the 
anterior  surface  of  the  lens.  The  cornea,  on  the  other  hand,  undergoes 
no  change  whatever.  These  observations  may  then  be  repeated  by 
actually  measuring  the  curvature  of  these  refracting  surfaces  on  far 
and  near  vision. 

Changes  in  accommodation  may  also  be  effected  by  stimulating  the 
excised  eye  electrically.  Most  commonly  we  employ  for  this  purpose 
the  eye  of  a  terrapin,  which  is  adjusted  under  a 
magnifying  glass  by  means  of  two  fine  needles  in- 
serted vertically  through  its  corneal  sclerotic  junc- 
tion. These  needles  are  connected  with  the 
secondary  coil  of  an  inductorium  (Fig.  430).  On 
stimulation  -^ith  single  induction  shocks,  it  will 
be  seen  that  the  iris  is  pushed  far  forward  into  the 
aqueous  humor,  while  the  anterior  portion  of  the 
lens  bulges  prominently  through  the  pupillar 
orifice. 

One  of  the  most  interesting  proofs  of  accom- 
modation has   been   furnished    by   Langenbeck.^ 
It  consists  in  determining  the  form,  size  and  posi- 
tion of  the  images  of  a  brilliant  object  reflected 
Fig.  430.— DIAGR.A3I  from  the  different  refracting  surfaces  of  the  eye. 
iLLrsTRATixG    THE  Thus,  If  SL  caudk  is  held  at  a  distance  of  about  50 
ox'^rSiTxioTor''^'  cm.  lateraUy  in  front  of  the  eye  of  the  observed 
Ciliary  Body.  person,  while   the  observer  places  himself  at  an 

A,  the  eye  at  rest;  angle  of  15°  to  20°  to  the  visual  axis  opposite 
B    during  stimulation  ^^    candle,  three  images  of  this  object  will  be  ol> 

the  lens  forces  its  con-  i 

vexity   through   the  taiued,  namely, 

pupillar  orifice,  pushing 

the  iris  forward.  {a)  A  bright  upright  image  from  the  surface  of  the 

cornea, 
(6)  a  large  upright  but  faint  image  from  the  anterior  surface  of  the  lens,  and 
(c)  a  small  inverted  and  faint  image  from  the  posterior  surface  of  the  lens. 

The  first  is  very  prominent,  while  the  other  two  are  less  distinct,  but 
can  usually  be  seen  without  much  trouble  by  properly  adjusting  the 
position  of  the  candle.  With  this  arrangement,  the  large,  faint  up- 
right image  from  the  anterior  surface  of  the  lens,  occupies  the  center 
of  the  pupil,  while  the  faint  inverted  image  from  the  posterior  sur- 
face of  the  lens  Hes  very  close  to  the  margin  of  the  pupil  opposite  the 
observer.  The  relative  size  and  position  of  these  images  ha^'ing  been 
clearly  ascertained,  the  observed  person  is  asked  to  accommodate 
alternately  for  near  and  far  objects  (Fig.  431).     TVTien  this  is  done,  it 

iXlin.   Beitrage  zur  Chir.  und  Ophthalm.,  Gottingen,  1849;  also  see:  Helm- 
holtz,  Monatsber..  Beriiner  Akad.,  1S53. 


THE    CILIARY   BODY    AND    LENS 


825 


will  be  found  that  on  near  vision  the  corneal  image  (a)  retains  its  po- 
sition, size  and  form,  while  the  one  reflected  fronx  the  anterior  surface 
of  the  lens  (6),  becomes  smaller  in  size  and  more  rounded,  and  moves 
toward  the  corneal  image.  A  very  slight  diminution  in  size  is  also 
displayed  by  the  image  reflected  from  the  posterior  surface  of  the  lens 


Fig. 


431. — Reflected  Images  of  a  Candle  Flame  as  Seen  in  the  Pupil  of  an  Eye  at 
Rest  and  Accommodated  for  Near  Objects.     (Williams.) 


(c).  It  need  scarcely  be  mentioned  that  these  changes  are  associated 
with  a  constriction  of  the  pupil  (Descartes,  1637),  and  that  all  the 
aforesaid  alterations  are  reversed  on  far  vision.  Since  near  vision  is 
an  active  muscular  process,  it  is  accomplished  less  speedily  than  the 
accommodation  for  far  objects. 


Fig.  432. — Diagram  Explaining  the  Change  in  the  Position  of  the  Image  Reflected 
from  the  Anterior  Surface  of  the  Crystalline  Lens.     (Williams,  after  Bonders.) 

The  lesson  to  be  derived  from  this  experiment  is  that  the  curvature 
of  the  cornea  remains  absolutely  the  same,  while  that  of  the  posterior 
surface  of  the  lens  suffers  only  the  slightest  possible  alteration.  By 
far  the  greatest  change  takes  place  at  the  anterior  surface  of  the  lens, 
which,  on  near  vision,  becomes  more  convex  and  therefore  forces  the 


826 


THE    SENSE    OF    SIGHT 


image  closer  to  the  cornea,  rendering  it  at  the  same  time  more  globular. 
These  observations  may  be  repeated  under  more  favorable  conditions 
by  making  use  of  a  darkened  triangular  box,  known  as  the  phacoscope 
(Helmholtz).  The  eye  to  be  observed  is  placed  in  the  orifice  at  A 
(Fig.  433)  and  is  directed  alternately  to  a  needle  situated  in  orifice  B 
and  to  a  distant  object  placed  in  the  prolongation  of  this  visual  line. 
Orifice  C  is  beset  with  two  prisms  which  throw  a  beam  of  light  into 
the  observed  eye.  The  observer's  eye  studies  these  images  through 
orifice  D.     They  appear  as  indicated  in  Fig.  434. 

Another  most  instructive  phenomenon  is  the  so-called  wabbhng 
of  the  lens,^  which  consists  in  a  declination  of  the  lens  or.  forced  near 

vision  of  from  0.28  to  0.3  mm.  This 
phenomenon  clearly  proves  that  ac- 
commodation diminishes  the  tension 
under  which  the  lens  is  held,  allow- 
ing its  weight  to  force  it  out  of  the 
central  axis  of  the  eyeball.  The 
direction  of  this  declination  depends 


B 
i 

Fig.  433.  Fig.  434. 

Fkj.  433. — Diagram  Illustrating  Course  of  the  Rays  Through  the  Phacoscope. 

A,  observed  eye;  B,  opening  allowing  accommodation  for  near  and  far  objects; 
C,  source  of  light;  D,  observer's  eye.  1,  images  from  cornea;  2,  anterior  surface  of  lens; 
3,  posterior  surface  of  lens. 

Fig.  434. — Diagram  of  Reflected  Images  as  Seen  in  Phacoscope. 
A,  during  far  vision;  B,  on  near  vision;  1,  image  from  cornea;  2,  image  from  anterior 
surface  of  the  lens;  3,  image  from  posterior  surface  of  the  lens. 

of  course  upon  the  position  of  the  head.  Thus,  when  in  the  erect 
position,  near  vision  would  allow  the  lens  to  drop  downward  com- 
mensurate with  the  degree  of  accommodation.  Subjectively  we  ob- 
serve this  phenomenon  only  under  unusual  conditions,  for  example, 
when  endeavoring  to  form  a  focus  of  those  shadows  which  are  ordi- 
narily produced  by  opaque  bodies  floating  through  the  aqueous  or 
vitreous  humor.  These  particles  then  appear  to  execute  jerky  motions 
in  space. 

In  addition,  it  might  be  mentioned  that  the  mechanism  of  accom- 
modation may  be  altered  by  drugs.     The  mydriatics  atropin,  homa- 
tropin  and  cocain  paralyze  the  ciliary  muscle  simultaneously  with  the 
1  Hess,  Archiv  fiir  Ophthalm.,  xliii,  1897,  477. 


THE    CILIARY   BODY    AND    LENS  827 

constrictors  of  the  pupil  and  retain  the  eye  in  a  condition  adapted  for 
far  vision.  Physostigniin,  on  the  other  hand,  stimulates  this  muscle 
and  renders  the  eye  near-sighted,* 

Scheiner's  Experiment. — An  experiment  which  illustrates  the 
process  of  accommodation,  as  well  as  the  projection  of  visual  impres- 
sions, is  the  one  described  by  Pater  Scheiner.  Two  small  holes  are 
made  in  a  cardboard,  the  distance  between  them  being  less  than  the 
diameter  of  the  pupil.  The  eye  then  looks  at  two  pins  placed  one 
behind  the  other,  at  a  distance  of  18  cm.  and  60  cm.  respectively. 


B -.-.-A-  — 


Fig.  435. — Diagram  to  Illustrate  Scheiner's  Experiment. 
The  continuous  lines  indicate  the  course  of  the  raj's  from  the  object  for  which  the 
eye  is  accommodated. 

If  one  pin  is  focalized  sharply,  the  other  appears  double.  A  glance 
at  Fig.  435  will  show  why  this  must  be  so.  Thus  if  the  eye  is  directed 
upon  the  near  pin  A ,  the  far  pin  B  is  brought  to  a  focus  in  the  vitreous 
humor  after  which  the  rays  again  diverge  and  strike  the  retina  in  two 
places,  C  and  D.  If  opening  1  is  now  blocked,  the  lower  retinal  image  D 
disappears  and  hence,  also  the  image  projected  into  space  on  the  side 
of  the  block.  If  the  eye  is  now  accommodated  for  the  far  pin  B,  the 
near  pin  A  is  focalized  behind  the  retina,  the  still  divergent  rays 
striking  the  retina  in  points  E  and  F.  It  will  be  seen  that  blocking 
opening  1  will  now  cut  out  the  upper  retinal  image  E,  and  hence,  the 
image  projected  into  the  visual  field  opposite  to  the  block. 

The  Changes  in  the  Shape  and  Refractive  Power  of  the  Lens. — 
The  changes  in  the  shape  of  the  lens  may  be  deduced  from  the  following 

^  One  of  the  earliest  theories  pertaining  to  accommodation  proposes  that  this 
process  necessitates  a  lengthening  and  shortening  of  the  entire  eyeball,  brought 
about  by  the  pressure  of  the  contracting  extrinsic  muscles  of  the  eye.  By  a 
process  of  exclusion,  we  have  shown  above  that  the  lens  is  the  essential  factor 
concerned  in  accommodation.  It  would  be  difficult  to  disprove  the  facts  brought 
forth  in  support  of  this  view ;  rnoreover,  since  an  accommodation  for  an  object  held 
at  a  distance  of  15  m.,  would  entail  a  lengthening  of  the  eyeball  of  not  less  than  2 
mm.,  it  seems  hardly  possible  that  such  a  change  could  be  brought  about  by  means 
of  the  normally  contracting  muscles  of  the  eyeball.  Electrical  stimulation,  per- 
formed under  experimental  conditions,  might,  however,  accomplish  this  end. 
This  view  has  recently  been  resurrected  by  Bates  (New  York  Med.  Jour.,  ci,  1915). 


828  THE    SENSE    OF    SIGHT 

ophthalmometric  measurements,  giving  the  radius  of  curvature  of  the 
chief  refracting  media: 

Near  vision  Far  vision 

Radius  of  curv.  of  cornea 8  mm.  8     mm. 

Radius  of  curv.  of  ant.  surface  of  lens 10  mm.  6     mm. 

Radius  of  curv.  of  post,  surface  of  lens 6  mm.  5.5  mm. 

The  lens  of  a  relaxed  eye  measures  3.025  to  4.43  mm.  in  thickness, 
average  3.6  mm.  On  near  vision,  its  anterior  surface  is  carried  for- 
ward thi'ough  a  distance  of  0.36  to  0.44  mm.;  hence,  it  will  be  seen 
that  the  thickness  of  the  lens,  when  accommodated  for  near  objects,  is 
increased  by  about  0.4  mm.,  i.e.,  on  the  average  from  3.6  mm.  to  4.0 
mm.  This  implies  that  its  anterior  surface  is  then  situated  at  a  dis- 
tance of  only  3.2  mm.  behind  the  cornea,  while  this  same  distance  in 
the  eye  at  rest  measures  3.6  mm.  Its  posterior  surface  lies  7.2  mm, 
behind  the  cornea  during  far  vision  and  retains  this  position,  at  least 
practically  so,  during  near  vision. 

This  change  in  the  shape  of  the  lens  is  dependent  upon  its  inherent 
elasticity,  and  especially  upon  that  of  its  capsular  investment.  This 
property  it  is  permitted  to  bring  into  play  as  soon  as  the  tension  under 
which  it  is  ordinarily  held  by  the  structures  of  the  zonula  Zinnii,  is 
diminished.  Since  its  refractive  power  is  increased  thereby,  the  enter- 
ing rays  of  light  must  be  rendered  more  convergent.  Under  ordinary 
conditions  we  express  the  refractive  power  of  a  lens  in  terms  of  its 
principal  focal  distance,  A  lens  possessing  a  focal  distance  of  one 
meter,  is  said  to  have  a  refractive  power  of  one  diopter  (D,).  Taking 
this  value  as  a  unit,  a  lens  with  a  focal  distance  of  50  cm.  possesses 
a  refractive  power  of  2D.,  one  with  a  focal  distance  of  10  cm.,  a  re- 
fractive power  of  lOD.,  and  conversely,  one  with  a  focal  distance  of 
10  m.,  a  refractive  power  of  O.lD.  (J^qD-)- 

Range  of  Acconrniodation. — The  ciliary  mechanism  fulfills  the 
purpose  of  bringing  any  object  in  space  to  a  precise  focus  upon  the 
retina,  but,  naturally,  it  cannot  simultaneously  produce  a  sharp  image 
of  two  objects  which  are  situated  at  different  distances  from  it.  We 
can  readily  convince  ourselves  of  this  fact  by  looking  at  a  distant 
object  through  a  network  of  fine  wire  held  hear  our  eyes.  If  we 
glance  at  the  distant  object,  the  wire  network  loses  its  clear  contours. 
Contrariwise,  if  we  look  at  the  network,  the  object  becomes  blurred. 

The  distant  point  in  space  at  which  an  object  is  still  clearly  dis- 
cernible, is  called  the  far-poini  or  punctum  remotum.  Quite  similarly, 
the  point  nearest  the  eye  at  which  an  object  still  produces  a  perfectly 
clear  impression,  is  known  as  the  near-point  or  punctum  proximum. 
In  between  these  two  extremes  lies  the  range  of  distinct  vision,  or 
range  of  accommodation.  Any  object  situated  beyond  the  far  point 
or  inside  the  near  point,  cannot  be  brought  to  a  precise  focal  point 
upon  the  retina  and  must,  therefore,  appear  blurred. 

The  Limit  of  Accommodation  of  the  Normal  Eye. — Inasmuch  as 
the  normal  or  emmetropic  eye,  when  at  rest,  is  adjusted  so  as  to  focus 


THE    CILIARY    BODY    AND    LENS  829 

parallel  rays  coming  from  the  distance,  its  far  point  must  lie  at  the 
horizon.  Consequently,  its  location  must  vary  with  those  outside 
factors  upon  which  the  visibility  of  objects  ordinarilj'-  depends.  Practi- 
cally, however,  it  has  been  found  that  an  eye  can  also  perceive  objects 
without  accommodation  which  are  situated  at  a  distance  of  only  6 
to  10  m.  from  it.  The  deduction  to  be  drawn  from  this  fact  is  that 
even  objects  situated  at  this  short  distance,  emit  a  large  number  of 
parallel  rays  which  the  eye  is  able  to  intersect  upon  the  retina  without 
actually  increasing  its  refractive  power.  In  this  action,  however, 
t^ie  different  refractive  media  are  aided  by  the  jnaterial  depth  of  the 
receptor.  In  other  words,  the  rods  and  cones  of  the  retina  upon 
which  the  light  impinges,  do  not  form  a  true  plane  but  possess  a  certain 
depth,  allowing  us  to  vary  the  anterior  focal  distance  in  a  slight 
measure  without  actually  causing  the  posterior  focal  point  to  fall 
entirely  outside  this  layer. 

If  the  object  is  now  moved  nearer  to  the  eye  than  the  aforesaid 
distance,  the  mechanism  of  accommodation  is  immediately  brought 
into  pla}'  with  the  result  that  the  now  divergent  rays  are  still  brought 
to  a  focus  upon  the  retina.^  The  closer  the  object  is  made  to 
approach  the  cornea,  the  greater  will  be  this  effort  at  accommodation 
until  its  physiological  limit  has  been  reached.  As  has  just  been  stated, 
the  nearest  point  at  which  the  eye  is  still  capable  of  forming  a  distinct 
image,  is  called  the  near  point.  Beyond  this  inner  limit  the  rays  of 
light  emitted  by  an  object,  are  so  divergent  that  they  can  no  longer 
be  brought  to  a  sharp  intersecting  point  upon  the  retina.  The  image 
then  appears  merely  as  a  diffused  area  of  light  which  fails  to  give 
a  proper  visual  impression. 

The  determinations  of  the  near-point  by  means  of  the  ophthal- 
momet«r  have  shown  that  it  does  not  retain  a  constant  position,  but 
varies  not  only  with  age,  but  also  with  the  general  condition  of  the 
body  and  local  defects  in  refraction.  At  birth,  the  lens  is  rather 
spherical  in  shape;  hence,  the  infant's  eye  should  really  be  adjusted 
for  near  objects,  were  it  not  for  the  fact  that  the  eyeball  is  at  this  time 
still  too  small.  In  reality,  these  two  factors  are  adjusted  in  such  a 
way  that  this  eye  is  somewhat  far  visioned.  Beginning  at  about  the 
age  of  10  years,  the  near  point  recedes  gradually  with  advancing  years 
and  more  markedly  between  the  fortieth  and  fiftieth  year.  This 
observation  is  more  fully  illustrated  by  the  following  figures: 

Age 

10  years —     7  cm.  in  front  of  cornea,  equalling  14      D.  refr.  power 

20  years —   10  cm.  in  front  of  cornea,  equalling  10      D.  refr.  power 

30  years — •  14  cm.  in  front  of  cornea,  equalling  7      D.  refr.  power 

40  years —  22  cm.  in  front  of  cornea,  equalling  4.5  D.  refr.  power 

60  years —  40  cm.  in  front  of  cornea,  equalling  2.5  D.  refr.  power 

60  years — 100  cm.  in  front  of  cornea,  equalling  1.0  D.  refr.  power 

^  The  term  retina  is  employed  here  as  well  as  elsewhere,  although  it  is  to  be 
clearly  understood  that  we  are  actually  referring  to  the  sensitive  inner  layer  of  the 
retina,  namely  to  the  rods  and  cones. 


830  THE    SENSE    OF    SIGHT 

This  gradual  restriction  of  the  range  of  accommodation  is  generally 
explained  by  saying  that  the  lens  loses  its  elasticity  with  advancing 
years.  While  this  is  true,  the  same  may  be  said  regarding  the  struc- 
tures of  the  zonula  Zinnii  and  the  constituents  of  the  ciliary  body. 
Senescence  is  a  common  phenomenon  in  nature  and  begins  with 
infancy,  although  dimmed  at  this  time  by  the  phenomenon  of  growth. 
Actual  disturbances  in  vision,  however,  do  not  arise  until  the  near 
point  has  receded  beyond  25  to  30  cm.,  i.e.,  until  about  the  forty-fifth 
year.  At  this  time,  most  persons  experience  certain  difficulties 
in  accurately  focusing  small  print.  This  condition  is  designated  as 
old-sightechiess  or  presbyopia.  It  indicates  that  our  ciliary  mechanism 
is  no  longer  capable  of  rendering  the  lens  sufficiently  convex  to  permit 
us  to  bring  near  objects  to  a  precise  focus  upon  the  retina.  Our  ac- 
commodation for  far  objects  remains  of  course  unimpaired.  This 
difficulty  in  refraction  may  be  remedied  by  the  employment  of  a 
biconvex  lens  of  a  strength  just  sufficient  to  overcome  the  senile 
flatness  of  the  lens. 

Late  in  life  the  lens  frequently  undergoes  certain  retrogressive 
changes  which  lead  to  an  opacity  of  its  substance.  When  fully 
developed,  this  condition,  known  as  cataract,  destroys  the  vision  com- 
pletely, because  it  prevents  the  rays  of  light  from  entering  the  fundus 
of  the  eye.  The  removal  of  this  now  useless  lens,  immediately  adjusts 
the  eye  for  far  vision,  because  it  is  then  wholly  dependent  for  its  re- 
fraction upon  the  cornea  and  the  aqueous  and  vitreous  humors.  All 
three  media  together,  however,  do  not  equal  the  refractive  power  of  a 
normal  lens.  An  eye  of  this  kind  may  again  be  converted  into  a  more 
useful  organ  by  placing  a  biconvex  lens  of  10  or  11  diopters  in  front  of 
it.  The  same  correction  must  be  made  for  an  eye,  which  has  never 
been  in  possession  of  a  lens.  This  inherited  condition  is  known  as 
aphakia. 

This  discussion  introduces  the  question  of  whether  the  near  point 
or  far  point,  as  determined  for  uniocular  vision,  remains  the  same 
when  both  eyes  are  used,  as  in  normal  binocular  vision.  Hess  has 
proved  this  to  be  the  case  whenever  the  two  visual  axes  are  converged 
in  a  symmetrical  manner,  but  not  when  we  look  laterally  outward. 
The  near  point  of  binocular  vision  is  then  situated  at  a  somewhat 
greater  distance  from  the  eyes. 

The  Innervation  of  the  Ciliary  Muscle. — Like  the  sphincter  pupillse, 
the  ciliary  muscle  derives  its  motor  impulses  from  the  anterior  part  of 
the  nucleus  of  the  oculomotor  nerve  in  the  midbrain!  These  pregan- 
glionic fibers  are  relegated  to  the  cihary  ganglion,  where  they  end  in 
arborizations  around  other  cells.  Postganglionically,  these  fibers  are 
continued  as  elements  of  the  autonomic  system  and  reach  their  desti- 
nation by  way  of  the  short  ciliary  nerves.  This  distribution  accounts 
for  the  close  interaction  between  the  ciliary  muscle  and  the  constrictor 
of  the  pupil;  near  vision,  as  has  been  shown  above,  being  associated 
with  a  constriction  of  the  pupil.     It  also  explains  the  simultaneous  con- 


THE    RETINA  831 

vcrgence  of  the  visual  axes  of  the  two  eyes  on  near  vision  by  the  recti 
interni  muscles.  All  these  actions  are  controlled  by  a  common  co- 
ordinating center. 

It  is  also  of  interest  to  note  that  the  activity  of  this  center  is  under 
the  guidance  of  the  will  and  is,  thei-efore,  controlknl  by  the  cerebrum. 
This  must  seem  peculiar,  because  the  effector,  the  ciliary  muscle,  is 
composed  of  smooth  muscle  tissue.  It  must  be  admitted,  however, 
that  these  reactions  are  usually  preceded  by  visual  sensations.  In 
other  words,  most  persons  cannot  effect  these  changes  in  the  eyes 
unless  guided  by  objects  in  space.  This  observation  might  lead  us  to 
suppose  that  the  act  of  accommodation  isasimplereflex,  just  because 
the  motor  actions  upon  which  it  is  based,  seem  to  necessitate  certain 
sensor}^  hnpressions.  In  reality  this  is  not  true,  because  we  can  easily 
learn  to  accommodate  without  first  directing  our  eyes  to  near  and  far 
objects  by  simply  making  volitional  efforts  in  a  dark  room,  or  after 
our  eyes  have  been  shaded.  Under  ordinary  conditions,  therefore,  the 
process  of  accommodation  belongs  to  the  group  of  the  psychical  reflexes 
or  association  reflexes.  As  such,  it  occupies  a  position  intermediate 
between  the  voluntary  responses  effected  by  means  of  striated  muscle, 
and  the  perfectly  involuntary  reactions  accomplished  with  the  help 
of  smooth  muscle. 


CHAPTER  LXXI 
THE  RETINA 


The  General  Structure  of  the  Retina. — The  retina  is  a  delicate 
membrane  containing  those  elements  which  are  absolutely  essential 
for  the  reception  of  the  rays  of  light  and  for  the  transfer  of  the  impres- 
sions evoked  by  them  to  the  center  of  sight  in  the  occipital  cortex  of 
the  cerebrum.  It  occupies  the  space  between  the  choroid  coat  and 
the  hyaloid  membrane  of  the  vitreous  humor,  and  extends  forward  to 
near  the  posterior  margin  of  the  ciliary  body.  It  terminates  here  in 
the  so-called  ora  serrata.  Its  thickness  increases  gradually  from 
before  backward,  namely  from  0.1  mm.  near  the  ciliary  body  to  0.4 
mm.  upon  the  posterior  expanse  of  the  eyeball. 

In  cross-section  it  presents  eight  distinct  layers,  namely : 

(a)  The  fiber  layer,  composed  of  nerve  fibers  striving  toward  their  common 
point  of  exit,  the  porus  opticus. 

(6)  The  laj^er  of  nerve  cells,  forming  the  ganglion  nervi  optici. 

(c)  The  inner  molecular  layer  (stratum  reticulare  int.). 

(d)  The  inner  nuclear  layer,  formed  by  bipolar  cells  (stratum  granularum  int.). 
(c)  The  outer  molecular  layer  (stratum  reticulare  ext.). 

(/)  The  outer  nuclear  layer  (stratum  granularum  ext.). 

(g)  The  layer  of  rods  and  cones. 

[h)  The  layer  of  hexagonal  pigment-cells  (stratum  nigrum). 


832 


THE    SENSE    OF    SIGHT 


The  nen'e  fibers  derived  from  the  different  regions  of  the  hemLspherically 
expanded  retina,  leave  at  the  optic  pore  where  they  pierce  the  other  two  coats  of  the 
eyeball  and  are  continued  onward  as  the  optic  nerve.  Inside  this  point  they  are 
not  in  possession  of  a  medullar}'  sheath  nor  of  a  neurolemma.  Most  of  these  fibers 
are  formed  by  the  a.xis  cylinder  processes  of  the  cells  of  the  second  la^'er,  but  some 
also  originate  in  the  inner  molecular  and  inner  granular  layers.  The  ganglion  cells 
of  the  second  layer  differ  greath'  in  their  size  and  shape,  their  single  imbranched 
axones  entering  the  fiber  layer.  They  are  especially  numerousin  the\'icrnity  of  the 
yellow  spot,  where  they  are  arranged  in  three  consecutive  rows.  The  inner 
molecular  layer  is  granular  in  its  appearance  and  is  made  up  of  the  arborescent 


Vuter  or  choroidal  surface. 


>n.l^ 


%-■       rrul.x 
Inney  or  vUrp.nus  surface. 

Fig.  4.36. — DiAGRAiiMATic  Sectiox  of  the  HuiiA>r  PlEtina.     (Schultze.) 


terminations  of  the  processes  of  the  cells  constituting  the  two  neighboring  laj'ers. 
The  inner  nuclear  contains  two  types  of  closely  packed  cells  of  which  the  bipolar 
tj^pe  is  the  most  conspicuous.  Their  inner  processes  usually  extend  to  the  internal 
molecular  layer  within  which  they  terminate  in  the  \-icinity  of  its  ganglion  cells. 
Their  outer  proces.ses  are  usually  thicker  and  pursue  a  more  direct  course  to  the 
outer  molecular  layer,  where  they  arborize  together  with  the  horizontal  cells  of  the 
inner  nuclear  laj'er.  The  outer  molecular  presents  an  appearance  similar  to  that 
of  the  inner  molecular,  but  is  not  quite  so  thick.  The  outer  nuclear  layer  consists 
of  nuclear  corpuscles  ha\'ing  an  oval  or  elliptical  shape.  They  are  known  respec- 
tively as  the  rod-granules  and  cone-granules.  The  former  are  the  more  numerous 
and  appear  as  swellings  upon  the  dehcate  fiber  emitted  by  the  rods  of  the  outermost 


THE    RETINA 


833 


layer  of  the  retina.  The  cone-pranules  are  more  pyriform  in  shape,  non-striated 
and  lie  in  close  opposition  to  the  external  limiting  mcnibranc  and  the  bases  of 
the  cones.  Their  inner  proce.sses  are  continued  into  the  outer  zone  of  the  outer 
molecular  layer,  where  they  terminate  in  a  prominent  varico.sity. 

The  outermost  layer  of  the  retma  consists  of  the  rods  and  conr.s.  The  former 
are  elongated  cylindrical  m  shape  and  measure  about  0.06  mm.  in  length  and  0.002 
mm.  in  width.  The  latter  are  shorter  and  thicker  and  measure  0.0;i5  mm.  in 
length  and  0.006  mm.  in  breadth.  Both  present  an  outer  and  an  inner  limb,  the 
former  being  imiiedded  in  the  neighboring  pigment  layer.  The  processes  derived 
from  the  inner  limbs  of  the  rods,  pass  into  the 
nuclei  of  the  outer  nuclear  layer.  A  central  fiber 
extends  from  here  into  the  outer  molecular  laj'er, 
where  it  ends  in  a  knob-like  structure.  The  pro- 
cesses from  the  inner  limbs  of  the  cones  traverse 
the  external  nuclear  layer  and  terminate  in  a  broad 
expanse  in  the  outer  molecular  layer.  At  this  point 
connection  is  made  with  the  bipolar  cells  of  the 
inner  nuclear  layer  by  means  of  short  fibers.^  But, 
since  the  retina  contains  many  millions  of  rods 
and  cones,  while  the  optic  nerve  embraces  onh- 
about  48,000  nerve  fibers,  these  peripheral  axones 
must  gradually  become  confluent. - 

The  cells  of  the  pigment  layer  measure  12  to 
18/i  in  diameter,  but  decrease  in  size  near  the 
yellow  spot.  Their  outer  surfaces  are  smooth, 
and  while  their  outer  portions  are  practically  free 
from  pigment,  their  inner  marginal  zones  are  packed 
with  it  and  present  filamentous  prolongations  ex- 
tending inward  along  the  limbs  of  the  rods  and 
cones.  The  former  are  almost  completely  sur- 
rounded by  this  pigmentous  material. 

While  we  shall  have  occasion  to  refer 
to  these  structural  details  later  on  in  con- 
nection with  the  theories  pertaining  to 
vision,  attention  is  called  to  the  fact  that 
the  retina  is  something  more  than  a  simple 
sense  organ;  in  fact,  its  complex  structure 
would  lead  us  to  believe  that  it  is  as  truly 
a  subdivision  of  the  brain  as  is  the  cerebral 
hemisphere  itself.  For  the  same  reason,  it 
may  be  concluded  that  the  optic  nerve  is 
not  a  simple  nerve  but  a  true  tract  of  the 
cerebrum.  In  this  system  the  rods  and  braxe.  (G.  Greeff.) 
cones  form  the  receptors,  and  hence,  con- 
stitute its  neurones  of  the  first  order,  while  the  cells  composing  the 
internal  granular  layer,  are  its  neurones  of  the  second  order  and  those 
of  the  zone  of  ganghon  cell,  its  neurones  of  the  third  order.  The  latter 
convey  the  impulses  to  the  ventral  aspect  of  the  brain  by  way  of  the 
optic  nerve,  whence  they  are  relayed  to:  (a)  the  cortical  center  for 
vision  through  the  thalamic  radiation,  (6)  the  roof  of  the  colHculus 

^Ladd  and  Woodworth.,  Elements  of  physiol.  Psychology,  New  York,  1911. 
2  Salzer,  Sitzungsber.,  Wiener  Akad.,  Ixxxi,  1880,  3. 


1. 


It. 


Fig.  437.— I,  A  Rod;  II,  A 
CoxE  OF  Maiimaliax  Retina; 
h.    External    Limiting    Mem- 


834 


THE    SENSE    OF    SIGHT 


of  the  midbrain  for  purposes  of  reflex  action,  and  (c)  the  pulvinar  and 
lateral  geniculate  bodies  of  the  region  of  the  thalamus.  These  connec- 
tions convert  the  optic  nerve  into  a  correlation  path  which  is 
comparable  to  the  lemniscus  system. 

The  Blind  Spot.^ — The  retina  derives  its  nerve  supply  from  the 
optic  nerve  which  pierces  the  eyeball  in  the  optic  disc  or  porus  opticus. 
Beginning  at  this  point,  its  fibers  spread  out  fan-like  across  the  entire 


a.  V 


sd  sec  n  se 


B 


Fig.  438. — Section  Through  the  Place  of  Extraxce  of  the  Optic  Xer\-e  (B), 
Together  with  the  Ophthalmoscopic  View  of  the  Disc  (A),  to  Show  the  Corre- 
SPOiroixG  Parts  of  the  Two.     {Fuchs,  after  Jaeger.) 

cd.  Lines  of  correspondence;  6,  depression  in  center  of  disc;  r,  retina;  ch,  choroid; 
si,so,  inner  and  outer  parts  of  the  sclerotic  coat,  s;  ei,  a  ciliary  artery  cut  longitudinally; 
a,»,  central  artery  and  vein;  sd,  subdural  space;  sa,  subarachnoid  space;  du,  dural 
sheath;  ar,  arachnoidal  sheath  of  nerve;  p,  pial  sheath;  n,  nerve-bundles;  se,  septa 
between  them. 


expanse  of  this  membrane.  The  circumference  of  this  disc  is  slightly 
elevated,  while  its  center  shows  a  depression  from  which  the  blood- 
vessels pass  radially  outward  toward  the  ora  serrata.  Its  diameter 
measures  about  1.8  mm.  When  looked  at  from  in  front,  it  appears 
as  a  whitish  circle  surrounded  by  a  dark  ring,  the  latter  indicating  the 
Une  where  the  pigmented  choroid  begins.  Inasmuch  as  this  entire 
area  is  composed  solely  of  nerve  fibers,  blood-vessels  and  reticular  tissue 

^  The  blind  spot  of  the  eye  was  discovered  by  Mariotte  in  1668  (M6m.,  Acad, 
de  Paris,  1669). 


THE    RETINA  835 

and  contains  no  other  retinal  element,  it  is  insensitive  to  light.  Nerve 
fibers  as  such  cannot  be  activated  by  the  ethereal  impacts  of  light. 
The  presence  of  the  blind  spot  may  be  demonstrated  in  several 
ways.  Donders/  for  example,  proj(%'ted  the  rays  of  a  small  flame 
alternately  upon  the  entrance  of  Ww  optic  nerve  and  upon  the;  general 
expanse  of  the  retina.  The  individual  received  no  sensation  of  light, 
when  the  image  was  localized  upon  the  former  area.  Another  way 
is  this:  If  the  left  eye  is  closed,  while  the  right  eye  gazes  steadily  at 
the  crossed  lines  of  Fig.  439,  the  white  circle  situated  about  8  cm. 
to  the  right  of  this  mark,  becomes  invisible  as  soon  as  the  figure  is 
held  at  a  distance  of  about  25  cm.  from  the  eye.  In  other  words,  the 
disappearance  of  this  circle  can  only  take  place  if  the  figure  is  placed 
at  a  distance  about  3  times  greater  than  that  between  the  cross  and  the 
circle.  If  the  latter  are  separated  more  widely,  the  figure  must  be 
moved  farther  away  from  the  eye  and  vice  versa.  Furthermore,  if  the 
opposite  eye  is  employed,  the  figure  must  be  reversed,  because  the  optic 
nerve  leaves  the  eyeball  on  the  nasal  side  of  a  horizontal  line  drawn 
through  the  anterior  and  posterior  poles  of  the  eye. 


Fig.  439. — Diagram  to   Demonstrate  Presence  of  Blind  Spot  in  the  Visual  Field. 
Fix  the  cross  with  the  right  eye;  bring  figure  closer  to  eye  until  the  white  dot  dis- 
appears.     (HelmhoUz.) 

Obviously,  therefore,  the  visual  field  of  each  eye  must  possess  an 
indifferent  area  corresponding  to  the  projection  of  the  optic  disc  into 
space.  But,  this  projection  does  not  give  rise  to  a  dark  patch  in  space, 
nor  to  a  similar  impression  in  consciousness  but  appears  merely  as  an 
area  devoid  of  stimulation,  i.e.,  as  a  small  hole  in  the  visual  field  with- 
out any  apparent  details.  Under  ordinary  conditions,  this  defect  is 
not  apparent,  because,  when  gazing  at  an  object,  we  always  deviate 
the  eye  in  such  a  way  that  the  rays  of  light  emitted  by  it  fall  upon  the 
most  sensitive  part  of  the  retina,  which  is  the  yellow  spot.  Conse- 
quently, the  blind  spot  must  occupy  at  this  time  a  place  in  our  indirect 
field  of  vision.  In  binocular  vision,  the  conditions  are  even  more 
favorable,  because  while  an  object  or  part  of  it,  may  fall  upon  the 
blind  spot  of  one  eye,  it  cannot  also  do  this  in  the  opposite  eye.  Hence, 
the  blank  in  the  field  of  vision  of  one  eye  is  always  filled  in  by  the 
other  eye.  A  similar  compensation  is  effected  in  the  psychic  center  for 
vision. 

The  size  and  shape  of  the  blind  spot  may  be  mapped  out  as  follows: 
Close  the  left  eye  and  fix  the  right  eye  upon  a  mark  upon  a  sheet  of 
'  Onderzock.,  Physiol.  Labor.,  Utrecht,  vi,  1852,  134. 


836  THE    SENSE    OF    SIGHT 

white  paper  held  at  a  moderate  distance  vertically  in  front  of  it.  By 
now  slowly  moving  the  head  of  a  pin  inward  along  the  horizontal 
plane  of  this  field,  a  point  will  presently  be  reached  when  it  suddenly 
disappears  from  the  view  and  later  on,  a  second  point,  when  it  reappears. 
By  repeating  this  procedure  along  the  vertical  and  oblique  planes,  the 
margins  of  this  indifferent  area  in  space  may  be  mapped  out  in  its 
entirety  (Fig.  4-40).  By  projection  it  then  becomes  possible  to  calcu- 
late the  position  and  size  of  the  optic  disc.  It  will  be  found  that  ob- 
jects of  the  size  of  a  5  cent  piece  may  be  made  to  disappear  when  held 
at  a  distance  of  about  25  cm.,  and  objects  of  the  size  of  the  head  of  a 
man,  when  placed  at  a  distance  of  about  2  m.  The  slight  irregularities 
in  the  contours  of  this  projected  figure  of  the  blind  spot  are  due  to 
the  interception  of  the  light  rays  by  the  blood-vessels  as  they  cross  the 
margin  of  the  optic  papilla. 


Au 


Fig.  440. — Form  of  the  Blind  Spot.     (HelmhoUz.) 

The  Yellow  Spot. — About  3.5  mm.  or  15  degrees  outside  the  blind 
spot  and  1  mm.  above  the  level  of  a  horizontal  line  drawn  through 
the  posterior  pole  of  the  eyeball,  lies  the  most  sensitive  area  of  the 
retina.  It  is  known  as  the  macula  lutea,  while  its  somewhat  depressed 
center  is  designated  as  the  fovea  centralis.  The  latter  measures  about 
0.2-0.4  mm.  in  diameter,  and  the  entire  area  about  2  mm.  Histo- 
logically it  is  noted  that  the  retina  of  this  region  is  greatly  thinned, 
retaining  in  the  fovea  centralis  merely  the  layer  of  the  rods  and  cones. 
Moreover,  it  is  observed  that  this  particular  area  is  made  up  exclu- 
sively of  cones  which  are  much  larger  than  those  situated  in  the  out- 
lying districts  of  the  retina.  They  are  so  closely  packed  that  they  give 
the  appearance  of  a  mosaic  of  hexagonal  prisms  (Heine).  The  fibers 
leaving  these  elements,  pursue  an  oblique  course  and  push  the  inner 
layers  of  the  retina  farther  toward  the  circumference  of  the  macula 
lutea,  so  that  the  cones  are  more  fully  exposed  to  the  entering  rays 
of  light.  ^  Outside  the  macula  the  cones  decrease  and  the  rods  in- 
crease in  number.  When  these  histological  characteristics  are  com- 
pared with  those  of  the  blind  spot  and  those  of  the  outlying  districts 
of  the  retina,  it  must  be  concluded  that  the  cones  are  the  most  im- 
portant factor  in   vision.     This  inference  finds  further  support   in 

1  Rochon-Duvigneaud,  Archives  d'anat.  micr.,  ix,  1907. 


THE   Hi-yriXA 


837 


certain  phononiona  connoct(>(l  with  dinn't  and  indirect  vision,  visual 
acuity  and  the  visual  sensations  produced  by  shadows. 

Direct  and  Indirect  Vision. — Under  ordinary  conditions,  the  fixa- 
tion of  an  object  is  acconiphshed  by  turniiig  our  eyes  in  such  a  direc- 
tion that  its  central  area  is  l)r()U}2;ht  to  a  focus  upon  the  fovea  centralis 
of  the  yellow  spot.  The  line  uniting  these  two  points  constitutes  the 
line  of  most  distinct  vision,  and  is  known  as  the  visual  axis  of  the  eye. 
Thus,  in  mapping  out  the  details  of  a  certain  visual  field,  we  invariably 
direct  our  eyes  first  to  one  object  or  a  part  thereof,  and  then  to  another. 
Only  that  object  gives  a  perfectly  clear  impression  at  any  one  time 
which  projects  its  raj^  of  light  along  the  visual  line  directly  into  the 


Tn,l.e 


i.||]in 


m.l.i 


Fig.  441. — Diagram  of  a  Section  Through  the  Fovea  C'extralis.  (The  outlines  of 
this  figure  have  been  traced  from  a  photograph.)  Magnified  350  diameters.  (From 
a  preparation  by  C.  H.  Golding-Bird.) 

2,  Ganglionic  layer;  4,  inner  nuclear;  6,  outer  nuclear  laj^er,  the  cone-fibers  forming 
the  so-called  external  fibrous  layer;  7,  cones;  m.l.e,  membrana  limitans  externa;  m.l.i., 
membrana  limitans  interna. 


fovea.  Meanwhile,  the  other  objects  of  this  particular  field  appear 
less  distinct,  because  the  rays  emitted  by  them,  form  too  great  an 
angle  with  the  visual  line  and  fall,  therefore,  upon  the  outlying  regions 
of  the  retina,  where  vision  is  less  acute.  In  reading  we  invariably 
fix  one  word  after  another.  Quite  similarly,  it  will  be  noticed  that  if 
we  gaze  at  a  single  word  upon  a  page,  the  other  words  remain  indistinct 
and  the  more  so,  the  greater  the  distance  between  them  and  the  one 
brought  to  a  precise  focus  upon  the  fovea.  The  imaginary  lines  which 
connect  the  outlying  luminous  points  of  an  object  with  the  more  periph- 
eral elements  of  the  retina,  constitute  secondary  visual  axes.     It  will 


838  THE    SENSE    OF    SIGHT 

be  seen,  therefore,  that  the  visual  appreciation  of  our  external  world 
is  accomplished  by  direct  and  indirect  vision.  The  former  leads  to  the 
formation  of  an  image  in  the  fovea,  and  the  latter  to  the  formation  of 
an  image  upon  the  more  outlying  districts  of  the  retina. 

This  discussion  clearly  shows  that  the  visual  axis  and  the  optical 
axis  of  the  eye  are  two  distinct  factors.  The  former  is  the  imaginary 
Hne  along  which  the  most  distinct  vision  is  obtained,  because  it  con- 
nects the  object  with  the  most  sensitive  area  of  the  retina,  the  fovea 
centralis  of  the  j^ellow  spot.  The  latter  is  the  line  of  most  perfect 
refraction,  because  the  different  refractive  media  of  the  eye  are  centered 
upon  it.  The  most  ideal  sj^stem,  of  course,  is  the  one  in  which  the 
refractive  media  are  adjusted  in  such  a  way  that  their  central  rays  are 
brought  to  a  precise  focus  upon  the  most  sensitive  region  of  the  re- 
ceptor. This  is  true  of  the  photographic  camera,  but  not  of  the 
human  eye,  because  the  latter  frequently  shows  a  divergence  of 
its  visual  and  optical  axes  of  from  3.5  to  7  degrees. 

Visual  Acuity. — Another  argument  in  favor  of  the  view  that  the 
cones  are  the  most  important  element  in  vision  is  presented  'by  the 
close  correspondence  between  the  smallest  possible  image  and  the 
disposition  of  the  cones  in  the  fovea.  Salzer^  has  shown  that  0.01 
mm-,  of  fovea  contains  138  cones,  and  that  an  illuminated  sheet  is  per- 
ceived as  such  only  if  each  cone  is  the  recipient  of  at  least  on^  ray  of 
light.  This  necessitates  about  140  rays  for  each  0.01  mm-,  of  foveal 
surface.  In  order  to  obtain  a  mosaic  impression,  the  different  cones 
must  be  invested  by  a  zone  of  non-stimulated  cones.  C.  DuBois- 
Reymond^  has  estimated  the  number  of  rays  then  required  at  72  per 
0.01  mm-,  of  foveal  surface.  Thus,  a  double  star  is  recognized  as  two 
distinct  bodies  only  if  the  distance  between  them  corresponds  to 
a  visual  angle  of  60  seconds.  Quite  similarly,  two  white  hues  drawn 
across  a  black  surface,  are  perceived  as  two  hues  only  if  the  distance 
between  them  subtends  a  visual  angle  of  64  to  73  seconds.  At  these 
angles,  the  image  covers  an  area  of  0.0045  to  0.0055  mm'-,  of  retina  and 
involves,  therefore,  two  cones  of  the  fovea.  These  experiments 
also  show  that  the  visual  acuity  does  not  differ  greatly  within  the  fovea, 
and  especially  not  within  the  foveola.  Outside  the  fovea,  however, 
the  acuity  diminishes  very  rapidly,  and  already  at  a  distance  of  20 
degrees,  the  hues  of  the  image  must  be  separated  by  a  distance  of 
0.035  mm.  in  order  to  produce  separate  impressions. 

Guillery  has  estimated  the  size  of  the  smallest  perceptible  image 
at  0.0035  mm^.,  this  value  being  apphcable  only  to  the  center  of  the 
fovea,  i.e.,  to  the  foveola.  For  this  determination  he  employed  a  black 
dot  upon  a  white  background  which  was  graduall}'  moved  away  from 
the  eye  until  it  just  barely  disappeared.  When  thus  just  barely 
producing  a  retinal  stimulation,  the  size  of  the  image  may  be  calculated 
by  correlating  its  distance  from  the  eyes  with  its  diameter.     Inde- 

'  Dissertation,  Berlin,  1881. 

2  Zeitschr.  fiir  Psych,  und  Physiol,  der  Sinnesorgane,  xii,  1896,  243. 


THE    RETINA 


839 


terminations  of  this  kind,  it  is  important  to  have  a  uniform  and  moder- 
ate intensity  of  illumination,  because  visual  discrimination  markedly 
increases  with  the  light  until  a  certain  upper  limit  has  been  reached. 

Purkinje's  Figures. — The  fact  that  the  sensory  elements  of  the  retina 
are  deeply  seated,  is  also  proved  by  the  phenomenon  commonly  known 
as  "Purkinje's  images."^  It  has  been  pointed  out  that  the  blood- 
vessels of  the  retina  ramify  upon  its  inner  surface,  whereas  the  rods 
and  cones  constitute  its  outermost  layer.  Consequently,  it  might  be 
supposed  that  all  light  entering  the  eye  must  cast  a  shadowof  the  blood- 
vessels upon  these  sensitive  elements.  Actually,  however,  a  dis- 
turbance of  this  kind  is  obviated  by  the  fact  that  the  diameter  of  even  the 
largest  retinal  vessel  amounts  to  only  one-sixth  of  the  thickness  of  the 
retina,  while  the  diameter  of  the  pupil  equals 
only  about  one-fifth  of  the  distance  between 
this  orifice  and  the  fundus.  Under  ordinary 
conditions,  therefore,  the  rods  and  cones  are 
the  recipients  of  the  penumbra  of  the  blood- 
vessels, while  their  umbra  falls  upon  the  inner 
layers  of  the  retina.  Experimentally,  how- 
ever, we  can  make  use  of  two  or  three  differ- 
ent means  to  render  them  visible  by  throwing 
their  shadows  upon  parts  of  the  retina  not 
ordinarily  exposed  bj'  them. 

If  the  eye  is  turned  inward  and  is  directed 
upon  a  dull  background  while  the  attendant 
reflects  a  beam  of  light  upon  the  outer  sur- 
face of  the  sclera  directly  behind  the  cornea, 
an  arborescent  image  of  the  blood-vessels  of 
the  illuminated  part  of  the  e3^eball  will  be  ob- 
tained (Fig.  442).  In  this  case,  blood-vessel 
B  throws  a  shadow  upon  the  neighboring  re- 
tina opposite  the  beam  of  light  AB.     If  the 

latter  is  then  moved  one  way  or  another,  the  image  of  these  vessels  is 
shifted  in  the  same  direction.  Naturally,  this  stimulation  at  C  is 
projected  into  space  through  the  optical  axis  as  apparently  having 
come  from  D.  This  method  may  also  be  employed  to  calculate  the 
distance  between  the  blood-vessels  and  the  sensory  elements  of  the 
retina,  the  factors  necessary  for  this  calculation  being  the  distance  of 
the  background  from  the  eye,  the  dimensions  of  the  eyeball,  the  angle 
through  which  the  light  is  moved,  and  the  apparent  movement  of  the 
image  upon  the  screen.  The  values  obtained  in  this  way  vary  be- 
tween 0.17  and  0.36  mm.  Since  it  has  been  determined  by  histological 
measurements  that  the  rods  and  cones  He  at  a  distance  of  from  0.2  to 
0.3  mm.  below  the  blood-vessels,  we  have  every  reason  to  suppose 
that  the  rays  of  light  are  received  by  these  particular  constituents  of 
the  retina. 


Fig.  442. — Diagram  to 
Illustrate  Purkinje's  Fig- 
ures. 

A,  source  of  light;  B, 
blood-vessel;  C,  shadow 
thrown  by  it,  which  stimu- 
lation is  projected  to  D  upon 
the  screen. 


1  Beitr.  zur  Kenntniss  des  Sehens,  Prag,  1819. 


840  THE    SENSE    OF    SIGHT 

The  retinal  blood-vessels  may  also  be  rendered  visible  by  moving  a 
candle  to  and  fro  in  front  of  the  eye  while  gazing  upon  a  dark  back- 
ground. In  accordance  with  the  foregoing  discussion,  it  will  be  seen, 
however,  that  the  candle  must  be  held  well  to  one  side  of  the  visual 
line,  otherwise  the  shadows  of  the  vessels  cannot  be  made  to  fall 
upon  a  lateral  zone  of  the  retina  which  is  ordinarily  not  exposed  to 
the  stimulation  by  these  vessels. 

A  third  method  consists  in  permitting  a  beam  of  light  to  enter 
through  a  pin-hole  in  a  cardboard  held  directly  in  front  of  the  cornea. 
In  this  way,  sharply  defined  shadows  of  the  blood-vessels  will  be  thrown 
UDon  the  underlying  rods  and  cones,  but  even  now  it  is  necessary  to 
move  the  cardboard  rapidly  to  and  fro  in  front  of  the  eye,  so  that  the 
shadows  are  not  allowed  to  rest  upon  the  same  area  of  the  retina  for 
any  length  of  time. 

Chemical  and  Physical  Changes  in  the  Retina  on  Stimulation 
by  Light. — Having  established  the  fact  that  the  rods  and  cones  are 
the  elements  which  are  most  directly  concerned  with  the  transforma- 
tion of  the  light  stimulus  into  a  visual  impulse,  we  are  now  in  a  posi- 
tion to  study  the  manner  in  which  their  stimulation  is  brought  about. 
The  theories  pertaining  to  this  subject  may  be  classified  as  follows: 

1.  Mechanical  imprint  theory  which  holds  that  the  rays  of  Hght  produce  im- 
pressions upon  the  retina,  similar  to  those  resulting  when  the  tips  of  the  fingers 
are  made  to  impinge  upon  a  layer  of  gelatin. 

2.  Thermal  theory  which  proposes  that  the  rays  of  light  traversing  the  retinal 
elements,    generate    heat. 

3.  Electrical  theory  which  suggests  that  the  waves  of  light  are  transformed  into 
electrical  energy. 

4.  Chemical  imprint  theory  which  holds  that  the  rays  of  light  give  rise  to  chem- 
ical reductions,  the  retina  containing  the  phototropic  substances  necessary  for  the 
formation    of    this   imprint. 

Though  in  the  present  state  of  our  knowledge  no  absolutely  con- 
vincing proof  can  be  furnished  for  any  one  of  these  conceptions,  the 
chemical  imprint  theory  is  by  far  the  most  satisfactory,  because  we 
are  in  possession  of  certain  evidence  tending  to  support  it.  In  analogy 
with  the  sensitive  plate  used  in  photography,  it  is  assumed  that  the 
retina  contains  a  phototropic  substance  which  is  dissociated  by  the 
entering  rays  of  light.  The  question  may  then  be  asked,  whether  such 
a  substance  has  actually  been  isolated.  It  will  be  remembered  that  the 
outer  poles  of  the  rods  and  cones  are  situated  upon  a  layer  of  pigment 
which  has  its  origin  in  the  adjoining  hexagonal  cells  of  the  choroid- 
retinal  junction.  This  pigment  possesses  a  reddish  color  in  amphibia, 
and  a  violet  color  in  fish,  owls,  sheep,  and  man."-  For  this  reason 
it  is  commonly  known  as  visual  jnivple  or  rhodopsin.  In  1876  BolP 
made  the  interesting  observation  that  this  formed  pigment  does  not 
remain 'stationary,   but  moves  in  and  out  of  the  aforesaid  cellular 

■    1  H.  Miiller,  Zeitschr.  fiir  wissensch.  Zoologie,  iii,  1851,  234. 
-  Sitzungsber.,  Akad.  der  Wissensch.,  Berlin,  1876. 


THE    RETINA 


841 


receptacles  along  definite  channels.  It  is  true,  however,  that  the 
latter  is  chiefly  associated  with  the  rods  and  is  absent  in  the  fovea 
centralis  which  is  wholly  composed  of  cones.  Since  wc  shall  have 
occasion  to  refer  to  this  point  again  later  on,  it  suffices  at  this  time  to 
note  that  a  dark  adapted  eye  presents  a  sharply  defined  Ijasement 
layer  of  pigment,  while  a  light  adapted  eye  shows  a  dissemination  of 
this  jiigment  In  between  the  rods  so  that  their  outer  poles  are  thor- 
oughly invested  by  it  ^  (Fig.  443).  Secondly,  it  has  been  observed 
by  Stort^  that  the  cones  are  contractile  and  move  outward  under  the 
influence  of  light.     Thus,  the  dark  adapted  eye  contains  these  elements 


^gm^^^^m 


III  llf  ITlfl 


mm^ 


Fig.  443. — Section  of  Frog's  Retina  Showing  the  Action  of  Light  upon  the  Pig- 
ment-cells, AND  upon  the  Rods  and  Cones.  Highly  Magnified,  (c.  Genderen-Stort.) 
A,  From  a  frog  which  had  been  kept  in  the  dark  for  some  hours  before  death.  B, 
from  a  frog  which  had  been  exposed  to  light  just  before  being  killed.  Three  pigment- 
cells  are  shown  in  each  section.  In  A  the  pigment  is  collected  towards  the  body  of  the 
cell;  in  B  it  extends  nearly  to  the  bases  of  the  rods.  In  A  the  rods,  outer  segments, 
were  colored  red  (the  detached  one  green) ;  in  B  they  had  become  bleached.  In  A  the 
cones,  which  in  the  frog  are  much  smaller  than  the  rods,  are  mostly  elongated;  in  B 
they  are  all  contracted. 

in  a  position  next  to  the  pigment  layer  and  retracted  in  between  the 
neighboring  rods,  while  the  light  adapted  eye  shows  them  in  close 
relation  with  the  membrana  Hmitans  externa. 

These  changes  may  be  demonstrated  very  easily  in  the  eyes  of 
frogs  which  have  been  kept  for  some  time  in  the  dark  or  have  been 
exposed  to  strong  dajdight.  After  its  removal  the  eye  is  quickly 
bisected  equatorially  and  placed  in  a  fixing  solution  and  subjected  to 
the  ordinary  histological  processes.  In  the  normal  eye,  the  visual 
purple  can  only  be  seen  in  fish,  because  the  layer  of  the  rods  and  cones 
is  here  situated  upon  a  white  tapetum.     In  man,  on  the  other  hand,  the 

^Kiihne,  Untersuchungen  aus  dem  physiol.  Institut  zu  Heidelberg,  1878. 
2  Ooderzoek,  Physiol.  Labor.,  Utrecht,  ix,  145. 


842  THE    SENSE    OF   SIGHT 

ophthalmoscope  is  of  no  avail,  because  the  perfectly  clear  retina 
lies  here  upon  the  dark  background  of  the  choroid.  Various  other 
means,  however,  are  at  our  disposal  to  show  that  this  pigment  is  a 
chemical  entity  serving  a  particular  purpose.  Thus,  it  will  be  found 
that  the  retina  of  an  eye  which  has  been  protected  against  hght  for 
some  time,  possesses  a  purple  color,  while  one  wliich  has  been  exposed 
to  strong  daylight,  is  entirely  colorless.  The  purple  color  of  the 
former  soon  becomes  yellowish  and  then  disappears  completely. 
This  bleaching  property  of  the  visual  purple  enables  us  to  employ  the 
retina  in  the  manner  of  a  photographic  plate,  but  naturally,  the  objects 
to  be  taken  must  show  sharp  contrasts.  Most  commonly,  we  employ 
the  eye  of  a  rabbit  or  frog  which  has  been  directed  for  a  brief  period  of 
time  toward  a  window,  preferably  one  w^th  many  cross-bars.  It  is 
then  bisected  and  immersed  in  a  4  per  cent,  solution  of  alum  which 
temporarily'-  fixes  this  inverted  image  of  the  window.  A  retinal 
photograph  of  this  kind  is  known  as  an  optogram  (Fig.  444). 


1  2 

Fig.  444. — Optogram  ix  Eye  of  Rabbit. 

1.     The  normal  appearance  of  the  retina  in  the  rabbit's  eye:  a,  The  entrance  of  the 

optic  nerve;  b,  b.  a  colorless  strip  of  meduUated  nerve  fibers;  c,  a  strip  of  deeper  color 

separating  the  lighter  upper  from  the  more  hea\dly  pigmented  lower  portion.     2  shows 

the  optogram  of  a  window.      (Howell.) 

It  has  pre%^ously  been  mentioned  that  the  \'isual  purple  is  pro- 
truded from  the  pigmental  epithehum  in  the  form  of  dehcate  processes 
which  invade  the  layer  of  the  rods  and  cones  and  closely  invest  the 
outer  hmbs  of  the  former.  It  cannot  surprise  us,  therefore,  to  find 
that  the  retina  of  the  Hght  adapted  eye  is  closely  adherent  to  the  choroid, 
while  that  of  the  dark  adapted  eye  maj^  be  easily  peeled  off.  Further- 
more, a  retina  which  has  been  bleached,  does  not  regain  its  original 
color  unless  it  is  allowed  to  remain  in  contact  with  the  pigmented 
epithehum.  These  data  clearly  prove  that  the  choroidal  pigment 
serves  as  the  mother-substance  of  the  visual  purple,  its  function 
being  to  supply  this  sensitive  substance  to  the  outer  limbs  of  the  rods 
as  quickly  as  it  is  reduced  bj'  the  hght  rays. 

The  visu-al  purple  may  he  extracted  from  the  retina  bj^  means  of 
solutions  of  bile  salts.  It  will  be  remembered  that  the  latter  possess 
the  power  of  quickly  abstracting  the  hemoglobin  from  the  red  blood 
corpuscles.  These  actions  are  verj^  similar,  in  the  present  case  the 
visual  pigment  being  Uberated  from  its  combination  in  the  rods.     The 


THE    RETINA  843 

solutions  thus  obtained,  contain  the  visual  purple  in  its  original  form 
and  may  be  bleached  l>y  exposing  them  to  light.  It  does  not  seem 
likely,  however,  that  this  reduction  gives  rise  to  distinct  bodies,  such 
as  have  been  designated  by  Kiihno  as  visual  yellow  and  visual  white. ^ 
A  dissolution  of  this  pigment  results  in  alkalies,  alcohol,  ether,  chloro- 
form and  most  acids.  It  is  resistant  against  ammonia,  sodium  chlorid, 
benzol,  fats  and  oils.  Even  the  different  rays  of  the  spectrum  affect 
it  in  an  unequal  measure,  red  and  orange  being  least  destructive 
and  yellow  and  green  most  destructive. 

The  Function  of  the  Visual  Phirple. — While  it  is  perfectly  obvious 
that  the  visual  purple  is  an  unstable  pigment  which  is  decomposed  by 
the  ethereal  impacts,  this  fact  does  not  furnish  an  adequate  explana- 
tion for  the  changes  resulting  in  the  rods  and  cones  in  consequence  of 
the  vibratory  energy  imparted  to  them  by  the  ether  waves.  Neither 
is  it  possible  to  recognize  in  this  pigment  a  substance  which  is  abso- 
lutely essential  to  vision,  because  it  is  absent  in  some  animals,  such  as 
the  pigeon,  hen,  certain  reptiles,  and  bats,  and  remains  wholly  confined 
to  the  rods.  Consequently,  since  the  fovea  centralis  is  composed 
exclusively  of  cones,  it  is  absent  from  this  area  which,  admittedly, 
is  the  place  of  most  acute  vision. 

These  discrepancies  force  us  to  assume  that  the  visual  purple 
serves  merely  as  a  sensitizing  substance  which  is  made  use  of  chiefly 
in  low  intensities  of  light.  It  is  a  well-known  fact  that  the  sensitiveness 
of  the  fovea  decreases  in  dim  light,  while  that  of  the  peripheral  expanse 
of  the  retina  increases.  In  other  words,  while  the  cones  are  employed 
in  day-vision,  the  rods  are  brought  into  more  general  use  in  low  inten- 
sities of  light.  In  semi-darkness,  therefore,  we  invariably  endeavor 
to  bring  the  image  into  the  peripheral  retinal  field  by  slightly  diverging 
the  eyes,  while  in  daytime  we  focalize  the  object  directly  upon  the 
yellow  spot.  This  shows  first  of  all  that  the  cones  themselves  are 
sensitive  to  light  and  need  no  sensitizing  substance  in  ordinary  light. 
Their  acuity,  however,  decreases  steadily  with  the  intensity  of  the 
light,  just  because  they  are  devoid  of  this  pigment.  For  this  reason, 
therefore,  the  yellow  spot  becomes  practically  blind  in  semi-darkness. 
By  analogy,  it  may  then  be  concluded  that  the  greater  sensitiveness 
of  the  peripheral  zone  of  the  retina  in  the  dark-adapted  eye  is  directly 
dependent  upon  the  production  of  the  visual  purple  and  its  movement 
to  the  outer  segments  of  the  rods.  By  virtue  of  this  pigment,  these 
elements  are  enabled  to  raise  the  otherwise  inert  light  rays  above  the 
threshold  of  stimulation.  In  this  connection,  brief  reference  should 
also  be  made  to  the  view  of  von  Kries,^  according  to  which  the  percep- 
tion of  color  is  distinctly  a  function  of  the  cones,  while  the  rods  are 
regarded  merely  as  playing  a  part  in  the  perception  of  white  light  of 

1  Abellsdorff  and  Kottgen,  Zeitschr.  f iir  Psj-chol.  und  Physiol,  der  Sinnesorgane, 
xii,  1896. 

2  Zeitschr.  flir  Phj'chol.  und  Physiol,  der  Sinnesorgane,  ix,  1895,  81. 


844 


THE    SENSE    OF    SIGHT 


low  intensity.     This  theory  will  be  more  fully  discussed  later  on  in 
connection  with  color-vision. 

Phosphenes. — It  has  been  emphasized  repeatedly  that  the  ade- 
quate stimulus  for  the  retina  is  the  light  ray,  because  this  receptor 
presents  the  most  favorable  conditions  for  the  transformation  of 
this  form  of  energy  into  nerve  impulses.^  In  a  slight  measure, 
however,  the  retina  is  also  accessible  to  inadequate  stimuli  in  the 
form  of  mechanical  and  electrical  impacts,  but  the  visual  impres- 
sions then  obtained  retain  the  character  of  very  general  sensations 
of  light.  These  sensations  are  of  course  subjective  in  their  quality, 
because  they  are  not  caused  by  homologous  stimuli  of  light,  but  by 
stimuli  of  a  heterologous  kind.     Thus,  if  the  eyelids  are  closed  and 

the  eyes  are  turned  inward,  any  pressure 
upon  the  external  part  of  the  eyeball,  such 
as  may  be  exerted  with  the  blunt  end  of  a 
pencil,  gives  rise  to  luminous  sensations, 
known  as  "phosphenes"  (Fig.  445).  In 
this  particular  case,  they  appear  in  the  form 
of  bright  yellowish  rings,  each  surrounding 
a  dark  center.  It  is  to  be  noted  especially 
that  this  sensation,  although  evoked  at  the 
point  of  pressure,  is  referred  to  the  opposite 
visual  field.  In  other  words,  any  pressure 
exerted  upon  the  outer  zone  of  the  eyeball 
gives  rise  to  a  sensation  which  is  projected 
into  the  nasal  area  of  the  visual  field,  be- 
cause under  ordinary  conditions  the  outer 
retina  is  stimulated  by  objects  situated  in 
the  nasal  field.  A  phosphene  of  similar 
character  may  be  produced  by  gazing  into 
a  bright  light  while  the  eyes  are  rapidly 
Inasmuch  as  the  eyeball  is  relatively  fixed 
at  the  point  where  the  optic  nerve  leaves  it,  this  abrupt  lateral  devia- 
tion gives  rise  to  a  mechanical  stimulation  of  the  retinal  elements  situ- 
ated around  the  edge  of  the  optic  disc.  In  this  case,  the  visual  sen- 
sation is  projected  directly  outward  into  the  central  visual  field. 
Phosphenes  also  result  in  consequence  of  stagnation  at  the  points  of 
exit  of  the  venae  vorticosse  and  in  consequence  of  the  pulsations  of 
the  retinal  arteries.  They  are  most  intense  in  conditions  of  hyper- 
excitability  of  the  general  nervous  system. 

Electrical  Variations  in  the  Eye  on  Vision. — The  retina  shows  a 
current  of  rest  or  injury  as  well  as  a  current  of  action.  If  an  excised  eye 
is  connected  with  a  galvanometer  by  two  non-polarizable  electrodes, 
one  of  which  is  adjusted  to  the  cornea  and  the  other  to  the  end  of 
the  optic  nerve,  the  latter  is  galvanometrically  negative  to  the  former. 

^  Klein,  Archiv  fiir  Physiol.,  1910.  531.  The  phenomenon  of  the  phosphenes 
has  been  known  since  the  time  of  Aristotle. 


Fig.  445. — Diagram  to  II- 
lx'strate  the  phenomenon  of 
Phosphenes. 

S,  The  mechanical  stimula- 
tion of  the  coats  of  the  eye  ball 
at  s  gives  rise  to  a  sensation  of 
light  which  is  projected  to  i  in 
the  opposite  visual  field. 

moved  from  side  to  side. 


THE    RETINA  845 

This  variation  is  the  ordinary  current  of  injury  caused  by  the  cutting 
of  the  optic  nerve.  At  this  time,  however,  this  nerve  is  galvanometri- 
cally  positive  to  the  lateral  zones  of  the  fundus  of  the  eyeball.'  Like 
all  living  tissues,  the  retina  also  becomes  the  seat  of  electrical  variations 
when  stimulated.  Thus,  the  falling  of  light  into  a  dark-adapted  ej^e 
gives  rise  to  an  electrical  change  which  may  be  regarded  as  analogous 
to  the  current  of  action  of  any  motor  or  sensory  nerve. ^  While  the 
nature  of  this  response  is  greatly  dependent  upon  the  strength  and 
duration  of  the  stimulus,  and  the  condition  of  the  eye,  it  generally 
results  after  a  latent  period  of  not  more  than  0.01  second. ■'  Its 
direction  is  the  same  as  that  of  the  preexisting  current  of  injury, 
provided  the  electrodes  have  been  applied  in  the  same  manner  as 
before.  Consequently,  since  it  passes  from  the  fundus  to  the  cornea 
and  thus  merely  intensifies  the  current  of  injurv,  it  forms  a  positive 
variation.  This  is  succeeded  by  a  gradual  diminution  and  later  on 
by  a  second  prolonged  increase.  Einthoven  and  Jolly^  who  have 
analyzed  this  current  with  the  aid  of  the  string  galvanometer, 
endeavor  to  explain  its  unusual  complexity  by  assuming  the  occur- 
rence in  the  retina  of  three  distinct  processes,  called  A,  B  and  C. 
The  first  develops  more  rapidly  than  the  other  two  and  is  especially 
marked  in  a  light-adapted  eye.  When  this  eye  is  stimulated,  it  gives 
rise  to  a  negative  and  when  darkened,  to  a  positive  potential  difference. 
The  second  process  is  less  speedily  initiated,  and  leads  to  a  positive 
variation  on  stimulation  and  a  negative  difference  on  darkening. 
This  process  is  brought  into  play  with  greatest  intensity  in  a  dark- 
adapted  eye,  when  it  is  illuminated  with  a  moderate  light.  The  third 
process  yields  the  same  results  as  the  second,  but  its  speed  of  develop- 
ment is  much  slower.     It  is  not  initiated  in  a  light-adapted  eye. 

When  the  non-polarizable  electrodes  are  adjusted  to  the  longitu- 
dinal and  cut  surfaces  of  the  optic  nerve  itself,  a  simple  negative  varia- 
tion is  obtained,  presenting  the  same  characteristics  as  the  ordinary 
action  current  of  nerve.  Peculiarly  enough,  however,  this  variation  is 
evoked  not  only  when  the  light  is  flashed  into  the  eye,  but  also  whon 
it  is  withdrawn.  Photo-electrical  phenomena  have  also  been  observed 
in  plants  when  alternately  darkened  and  lightened. ° 

1  Holmgren,  Zentralbl.  fur  Physiol.,  xi,  1897. 
2Gotch,  Jour,  of  Physiol.,  x.x.xi,  1904,  31. 
3  Nagel,  Handb.  der  Physiol,  190.5,  iii,  103. 
*  Quart.  Jour,  of  Exp.  Physiol.,  i,  1908,  373. 
^  Waller,  Proc.  Royal  Soc,  London,  Ixvii,  1900. 


846 


THE    SENSE    OF    SIGHT 


CHAPTER  LXXII 


THE  FORMATION  OF  THE  IMAGE  UPON  THE  RETINA 

The  Reduced  or  Schematic  Eye. — The  eye  consists  of  two  parts, 
namely,  the  hemispherieally  expanded  retina  with  its  mosaically  ar- 
ranged sensory  elements  and  a  number  of  adjuncts  which  form  a 
dioptric  mechanism  for  projecting  the  light  rays  upon  this  receptor. 
Having  previously  studied  the  structure  and  function  of  these  parts 
separately,  we  are  now  in  a  more  favorable  position  to  deal  with  them 
collectively  and  to  see  how  they  are  capable  of  forming  a  real  image  of 
external  objects  in  their  correct  spatial  relationships  upon  the  retinal 
surface.  This  analysis  should  not  be  attended  b}'  undue  difficulties, 
because  it  is  based  essentialh'  upon  the  data  pertaining  to  the  refrac- 
tion by  biconvex  lenses  given  in  one  of  the  preceding  chapters. 

The  normal  or  emmetropic  eye  is  constructed  in  such  a  way  that 
the  different  rays  of  light  are  brought  to  a  precise  focus  upon  the  retina. 

This  refraction,  however,  involves 
not  only  those  rays  which  pursue  a 
course  parallel  to  its  visual  axis,  but 
also  those  which  are  projected  toward 
it  in  a  divergent  direction  and 
would  otherwise  be  lost  to  it.  This 
power  it  exerts  by  virtue  of  its  ability 
to  accommodate  for  near  and  far 
objects.  But  while  the  process  of 
refraction  in  our  eye  is  essentially 
the  same  as  that  exhibited  by  bi- 
convex lenses,  the  fact  that  several 
media  take  part  in  it,  tends  to  make 
matters  more  difficult.  A  biconvex 
lens  changes  the  course  of  the  ray  in  two  places,  nameh*,  at  the  point 
where  the  latter  enters  the  denser  medium  and  again  where  it  leaves 
it.  Upon  its  passing  from  the  rarer  into  the  denser  medium  it  is 
refracted  toward  the  perpendicular,  and  upon  its  passing  from  the 
denser  into  the  rarer  medium,  away  from  the  perpendicular.  Our 
eye  contains  a  large  number  of  these  points  of  refraction,  chief 
among  which  are  the  anterior  surface  of  the  cornea  and  aqueous  humor, 
the  anterior  and  posterior  surfaces  of  the  lens,  together  with  the  an- 
terior surface  of  the  vitreous  humor  (Fig.  446).  In  fact,  the  entering 
ray  of  light  first  meets  with  a  laj^er  of  tears,  the  refractive  power  of 
which  is  considerable.  Inside  the  cornea  it  is  not  deviated  very  mate- 
rially, because  the  anterior  and  posterior  surfaces  of  this  medium  are 


Fig.  446. — DiAGR.\ir  to  Illustrate 
THE  Position  of  the  Chief  Porvrs  of 
Refraction  in  Our  Eye. 

A,  Cornea;  B,  anterior  surface  of 
lens;  C,  posterior  surface  of  lens. 


FORMATION  OF  THE  IMAGE  UPON  THE  RETINA      847 

practicall}^  parallel,  while  the  refractive  power  of  the  tears  and  aqueous 
humor  are  nearly  equal.  It  is  strongly  deviated,  however,  at  the 
anterior  and  posterior  surfaces  of  the  lens,  because  the  refractive 
indices  of  the  aqueous  and  vitreous  humors  are  less  than  that  of  the 
lens.  In  general,  the  refractive  power  of  this  entire  system  may  be 
calculated  without  difficulty,  provided  the  following  factors  are  open 
to  analysis: 

(a)  The  indices  of  refraction  of  the  difTerent  media. 

(b)  The  radii  of  the  different  curved  surfaces. 

(c)  The  distances  between  them. 

Regarding  the  first  factor,  the  following  values  have  been  obtained  :^ 

Air 1.0 

Cornea 1.3771 

Aqueous  humor 1 .  3374 

r  Capsule 1 .3599  ] 

Lens  I  Ext.  layer 1.3880  [  1.4371 

I  Body 1.4107  J 

Vitreous  humor 1 .  3360 

It  will  be  seen  that  the  indices  of  the  aqueous  and  vitreous  humors 

are  practically  the  same  and  correspond 

to  that  of  water.     Furthermore,  it  will  1? 

be   observed   that   the    total    refractive 

power  of  the   lens   (1.4371)    is    greater  X  J 

than  that  of  its  different  layers,  as  well  [     /iJM 

as  of  that  of  its  body.     This  apparent  T    Tj; 

discrepancy  is  explained  by  the  fact  that  V^'t 

its  central    substance,    when    isolated,  ^ 

possesses   a  greater   curvature  than  its 

entire  mass  and,  therefore,  gives  rise  to  a         j,^^  447-Diagr.^m  to  Illus- 

Stronger    refraction     in     relation     to     its     tr.\te  the   Reduced  or  Schematic 

index.  Era. 

In  order  to  simplify  matters  Listing2     ^.imaginary   refracting    surface; 
,  1-1,1  1  •  cc  ,  c         ,  -  - » .  nodal  point  of  this  system. 

has  combined  these  dmerent  retractive 

media  into  a  single  one  possessing  a  general  refractive  index  of  1.33. 
If  united  in  this  manner,  the  entire  eye  may  be  regarded  as  being 
composed  of  a  homogeneous  substance  presenting  to  the  air  a  single 
convex  surface  with  a  refractive  index  of  1.33,  and  a  radius  of  cur- 
vature of  5.017  mm.  (Fig.  447).  The  principal  point  of  the  re- 
fracting surface  of  this  reduced  or  schematic  eye  lies  2.1  mm.  behind 
the  anterior  surface  of  the  cornea,  and  its  nodal  point  (N)  or  optical 
center  0.04  mm.  in  front  of  the  posterior  surface  of  the  lens,  i.e.,  7.3 
mm.  behind  the  anterior  surface  of  the  cornea.  The  principal  focus 
of  this  imaginary  refracting  surface  lies  22.2  mm.  behind  the  anterior 
surface  of  the  cornea  of  the  actual  eye.     The  optical  power  of  this 

^  Matthiessen,  Pfliiger's  Archiv,  xxxvi,  1885. 

2  Wagner's  Handworterbuch  der  Physiol.,  1853,  iv,  451. 


848 


THE    SENSE    OF    SIGHT 


reduced  system  is  50.8  diopters,  and  hence,  the  focal  point  of  this 
eye,  when  accommodated  for  a  far  object  and  in  the  position  of  rest, 
lies  precisely  upon  the  retina. 

The  Formation  of  the  Retinal  Image. — In  reducing  the  eye  into 
this  simple  form,  Listing  has  followed  the  mathematical  expositions 
of  Gauss  ^  which  show  that  the  several  media  of  anj^  refractive  system, 
whenever  centered  upon  the  same  optical  axis,  maj^  be  considered  as 
forming  two  parallel  planes  possessing  an  equal  refractive  power 
(Fig.  448).  For  practical  purposes,  these  two  planes  (P)  with  their 
respective  nodal  points  (N)  may  be  regarded  as  being  coincident,  be- 
cause the  distance  between  them  is  actually  very  small  so  that  the 
refracted  ray  from  the  first  plane  is  sent  into  the  second  still  parallel  to 
the  optical  axis.  In  constructing  the  image  of  object  AB,  it  must 
be  remembered  that  any  luminous  point  upon  AB  sends  out  two  rays, 
one  of  which  passes  through  the  nodal  point  unrefracted,  while  the 


Fig.  448. — Diagrajm  to  Show  the  Iistv^er-  Fig.  449. — Diagram  to  Illus- 

siON  OF  THE  Image  by  Parallel  Refracting        trate  the  Construction   Neces- 

SURFACES.  SARY    TO  DETERMINE  THE  LOCATION 

AB,  object;  A^B\  image;  A',  nodal   point       ^^^  Size  of  the  Retinal  Image. 
of  two  parallel  refracting  surfaces  P;  F,  focal 
point. 

other  pursues  a  course  parallel  to  the  optical  axis  of  this  system  and  is 
then  refracted  through  its  focal  point  F.  At  the  point  of  intersection 
of  these  two  rays  (A  i)  lies  the  image  of  luminous  point  A.  If  this  con- 
struction is  repeated  for  luminous  point  B,  it  will  be  seen  that  the  image 
of  .45  is  inverted. 

The  same  construction  may  be  followed  in  the  reduced  eye  (Fig. 
449),  because  we  know  the  center  of  curvature  (n)  of  its  single  imaginary 
refracting  surface  (/?),  in  other  words,  its  nodal  point  through  which 
all  the  principal  rays  may  be  imagined  to  enter  the  eye.  These  rays 
are  not  deviated  from  their  course,  owing  to  the  fact  that  they  strike 
the  refracting  surface  at  right  angles.  Consequently,  all  that  is  required 
for  the  determination  of  the  position  of  the  image  of  an  object  upon  the 
retina,  is  to  draw  straight  lines  from  its  different  luminous  points 
through  the  nodal  point  n  It  is  evident  that  the  retinal  image  is 
inverted  and  that  its  size  will  be  the  smaller,  the  less  the  distance 
of  the  nodal  point  from  the  retina  and  the  greater  its  distance  from  the 
object.  Expressed  in  terms  of  the  visual  angle,  it  may  then  be  said 
^Dioptrische  Untersuchungen,  Gesellsch.  der  Wissensch.,  Gottingen,  1838-1843. 


FORMATION    OF    THE    IMAGE    UPON    THE    RETINA  849 

that  the  image  becomes  the  smaller,  the  less  this  angle.  Obviously, 
the  latter  nmst  vary  directly  with  the  size  of  the  object  and  inversely 
as  its  distance.  Thus,  if  we  gaze  first  at  the  moon  and  then  at  a  more 
distant  but  much  larger  fixed  star,  the  visual  angle  formed  by  the  rays 
from  the  moon  is  much  larger,  because  its  relative  proximity  to  the 
eye  more  than  makes  up  for  its  smaller  size. 

This  inversion  of  the  image  may  be  conveniently  demonstrated 
by  observing  a  landscape  upon  the  ground  glass  of  a  photographic 
camera.  Quito  similarly,  we  ma^^  employ  the  eye  of  an  albino  rabbit 
which  contains  no  choroidal  pigment  and  in  which,  therefore,  the 
image  may  be  seen  through  the  transparent  sclerotic  coat.  The 
question  may  then  be  asked,  why  do  we  not  perceive  objects  upside 
down?  Our  correct  interpretation  of  spatial  relationships  is  gained  in 
the  course  of  time  by  experience  and  in  consequence  of  the  association 
of  various  sensory  impressions.  In  other  words,  our  psychic  mech- 
anism is  adjusted  in  such  a  way  that  it  conforms  absolutely  to  this  in- 
version of  the  image.  Consequently,  any  ra}^  of  light  striking  the 
retina  below,  is  invariably  regarded  as  having  arisen  from  a  luminous 
point  situated  in  the  upper  visual  field.  Quite  similarh',  any  stimula- 
tion of  the  upper  expanse  of  the  retina  is  correctly  interpreted  as 
having  originated  in  the  lower  visual  field,  and  so  on. 

The  fixed  character  of  our  spatial  associations  may  be  proved  in 
different  ways.  Thus,  we  have  previously  observed  that  the  mechan- 
ical stimulation  of  the  retina  gives  rise  to  luminous  sensations  or  phos- 
phenes,  which  are  invariably  referred  to  the  visual  field  oppo.site  the 
seat  of  the  stimulation.  The  reason  for  this  is  that  these  elements  are 
invariably  stimulated  by  rays  which  are  projected  along  these  particu- 
lar secondary  lines.  In  localizing  these  retinal  stimuli  in  space,  it 
may  be  imagined  that  we  are  guided  by  the  local  signs  previously 
established  b}'  them  in  the  visual  center.  Like  the  receptors  of  the 
skin,  each  retinal  element  may  be  assumed  to  be  connected  wnth  a 
particular  central  neurone  which  in  the  course  of  time  has  become 
adapted  to  a  perfectly  definite  sensation.  Our  psychic  interpretation, 
therefore,  corresponds,  as  it  were,  to  a  reversal  of  the  rays  of  light,  i.e., 
the  stimulated  points  upon  the  retina  may  be  imagined  to  emit  rays 
which  pass  in  a  straight  line  through  the  nodal  point  and  form  an 
imaginary  image  in  space  in  accordance  with  their  secondary  axes. 

Another  good  illustration  of  this  general  fact  is  obtained  whenever 
objects  are  held  so  close  to  the  eye  that  the  ordinary  inverted  image 
must  give  wa}'  to  an  erect  shadow  (Fig.  450).  To  accomplish  this 
end,  a  card  wath  a  pin-hole  is  held  at  a  distance  of  about  3  cm.  in  front 
of  the  eye,  i.e.,  within  the  near  point  of  vision.  If  a  pin  is  now  moved 
slowly  upward  in  front  of  the  pupil  and  as  close  as  possible  to  the  cor- 
nea, the  pin  appears  to  enter  the  visual  field  from  above.  The  same 
result  is  obtained  if  the  object  is  moved  along  any  other  meridian  of 
the  cornea.  Since  the  pin-hole  lies  inside  the  near  point  of  this  eye, 
it  is  converted  into  a  source  of  light  which  widely  illuminates  the  ret- 

54 


850 


THE    SENSE    OF    SIGHT 


ina.  Inside  this  circle  of  light  upon  the  retina  lies  the  shadow  of  the 
pin  in  its  natural  position.  It  appears  inverted  for  the  obvious  reason 
that  the  retinal  elements  stimulated  by  this  shadow,  are  associated  in 
an  inverse  manner.  Consequently,  any  shadow  falling  upon  the  lower 
expanse  of  the  retina,  is  interpreted  as  having  been  produced  by  an 
object  situated  in  the  upper  visual  field. 


Fig.  450. — DiAGRAii  to  Illustrate  the  Formation-  .\.\d  pRojEr  tion  of  the  Shadow  of  a 

Pi.x. 
.4.,  Pm;  J ,  shadow  of  it  upon  lower  retina;  P,  projer-tefJ  as  if  moving  into  the  visual 
line  from  above. 

The  Size  of  the  Retinal  Image. — The  dimensions  of  the  image  of 
an  object  upon  the  retina  may  readily  be  ascertained  if  the  size  of  the 
object  and  its  distance  from  the  cornea  are  known  (Fig.  451).  Sup- 
posing that  the  object  AB  is  focused  upon  the  retina  in  A'B' ,  then  AB 
and  A'B'  really  form  the  bases  of  two  similar  triangles,  the  apices  of 
which  are  situated  at  the  nodal  point  of  the  lens,  while  its  sides  are 
formed  by  the  secondary  axes  AB'  and  BA'.  If  C  stands  for  the  dis- 
tance of  the  nodal  point  from  A,  and  D  for  the  distance  of  this  point 
from  B' ,  then: 

AB  ^  A'B' 

C    ~     D 


Fig.  4.51. — Diagr.vm  to  Show  how  the  Size  of  the  Retixal  Ima(;e  may  be  Determln'Ed. 


As  has  been  stated  above,  the  distance  of  the  image  from  the  nodal 

point  may  be  reckoned  at  about  15  mm.     Consequentlj',  an  object 

120  feet  in  height,  placed  at  a  distance  of  25  miles,  forms  an  image  upon 

the  retina,  the  dimen.sion  of  which  is 

120  ft.         _  .  120  ft.  _  1 

X  15  mm.,  I.e.  V7^^^?r~r^ c^,-  <-,    X  lo  mm.,  or 


25  miles 


5280  X  25  ft. 


1100 


X  15  mm.  = 
0.013  mm. 


FORMATION    OF    THE    IMAGE    UPON    THE    RETINA  851 

This  image,  therefore,  would  scarcely  equal  the  diameters  of  two  red 
corpuscles  and  would  cover  about  four  cones  of  the  fovea  centralis. 
This  same  object  placed  at  a  distance  of  one  mile  (5280  feet),  would 
give  an  image  measuring  0.341  mm.  in  height,  which  corresponds  to 
about  the  diameter  of  the  fovea  centralis. 

The  Visual  Field.  Perimetry. — If  our  attention  is  called  to  an 
object,  our  eyes  are  always  turned  in  such  a  way  that  its  central  area 
is  brought  to  a  precise  focal  point  in  the  foveae  centrales.  This  act 
constitutes  direct  vision.  At  this  very  time  all  other  objects  in  space 
fall  upon  the  outlying  districts  of  the  retinae  and  are  therefore  seen  by 
indirect  vision.  Direct  vision,  therefore,  is  effected  through  the  visual 
axis,  connecting  the  object  with  the  fovea,  and  indirect  vision  through 
secondarj^  axes  which  fall  upon  the  more  peripheral  zones  of  the  retina. 
Both  eyes  together  cover  a  certain  extent  of  the  external  world  which 
is  known  as  the  visual  field,  but  this  entire  field  is  really  made  up  of  two, 
a  right  and  a  left,  the  nasal  spheres  of  which  overlap.  From  what 
has  been  said  above  regarding  the  manner  of  refraction  in  our  eye,  it 
must  be  evident  that  the  retinal  image  is  inverted  and  that  objects 
situated  in  the  upper  extent  of  the  visual  field,  are  centered  upon  the 
lower  half  of  the  retina,  and  vice  versa.  The  same  is  true  of  objects 
situated  respectively  in  the  right  arid  left  halves  of  the  visual  fields, 
because  they  fall  upon  the  opposite  side  of  the  retina. 

The  configuration  of  the  entire  visual  field,  as  well  as  of  that  of 
each  eye,  depends  chiefly  upon  the  anatomical  characteristics  of  the 
margins  of  the  orbital  cavity.  Centrally,  each  field  is  restricted  by  the 
bridge  of  the  nose,  above  by  the  orbital  arch,  and  below  by  the  cheeks. 
Consequently,  each  field  really  presents  an  irregular  oval  outline,  in- 
stead of  a  circular  one  which  it  would  possess  if  the  eye  were  protruded 
beyond  these  restricting  boundaries.  Its  limits  may  be  ascertained  by 
steadily  gazing  with  one  eye  upon  a  mark  upon  a  large  cardboard, 
placed  at  a  distance  of  about  25  cm.  vertically  in  front  of  the  cornea. 
The  visual  axis  of  this  eye  should  strike  the  cardboard  exactly  at  right 
angles.  A  small  object  is  then  moved  from  without  along  the  vertical, 
horizontal  and  oblique  meridians  as  charted  upon  the  cardboard.  A 
mark  is  made  each  time  when  the  observed  person  obtains  a  clear 
impression  of  this  object.  If  these  outlying  points  are  then  joined 
with  one  another,  we  obtain  the  boundaries  of  the  visual  field  of  this 
particular  eye  at  the  distance  of  25  cm. 

An  instrument  commonly  made  use  of  for  mapping  out  the  visual  field  is 
the  perimeter.  The  one  devised  by  Aubert  and  Forster^  (Fig.  452),  consists  of  a 
hemispherical  band  of  metal  fastened  to  a  stand  and  movable  so  as  to  cover  the 
different  meridians  of  the  eye.  In  front  of  this  arc  is  placed  a  support  for  the  chin 
of  the  observed  person,  his  eye  being  adjusted  in  such  a  way  that  he  is  able  to  gaze 
horizontally  at  a  white  object  fastened  to  the  center  of  this  circle  (Fig.  452). 
A  small  white  disc  is  then  moved  slowly  from  without  along  this  arc  until  it  be- 
comes clearly  visible.  The  arc  is  graduated,  allowing  the  moment  of  the  appear- 
ance of  this  object  to  be  charted  (Fig.  453).     This  procedure  is  repeated  along  the 

1  Archiv  fur  Ophthalmologic,  iii,  1857. 


852 


THE    SENSE    OF    SIGHT 


other  meridians  until  the  boundaries  of  the  entire  visual  field  have  been  accurately 
mapped  out.^ 

Clinically  this  instrument  is  employed  for  determining  the  seat  of  lesions  of  the 
retina  or  of  the  optic  tract  and  visual  center.  Obviously,  any  defect  of  the  optic 
path  must  give  rise  to  a  retinal  area  of  indifference  and  hence,  to  a  dark  zone  within 
the  visual  field.  Thus,  it  will  be  remembered  that  unilateral  lesions  of  the  occipital 
cortex  give  rise  to  the  condition  of  hemianopia  or  half-blindness  of  the  retina  on 
the  corresponding  side.  If  their  right  halves  have  in  this  way  been  rendered 
functionally  useless,  the  left  halves  of  the  visual  fields  are  blotted  out.  Direct 
vision,  however,  is  retained,  because  each  fovea  centralis  is  connected  with  both 


oooo 


Fig.  4.52. — The  Perimeter. 

occipital  centers.  Very  similar  defects  in  the  visual  field  follow  injuries  to  the  opti- 
cal tract  or  to  the  retina  itself.  Thus,  the  occlusion  or  rupture  of  a  terminal  branch 
of  the  retinal  artery  most  generally  leads  to  a  uselessness  of  a  circumscribed  patch 
of  the  retina  with  a  corresponding  defect  in  the  -visual  field  of  this  eye.  This  defect, 
however,  cannot  become  apparent  unless  the  corresponding  area  of  the  opposite 
retma  has  also  been  mjured.  Admittedly,  the  two  retina?  act  in  unison  and  com- 
pensate for  minor  defects  so  long  as  the  mjury  remains  confined  to  one  of  them. 
This  functional  reciprocity  has  already  been  fully  discussed  in  the  paragraphs  deal- 
ing with  the  blind  spot.     It  was  then  found  that  while  a  certain  number  of  the  rays 


1  Peter,  Principles  and  Practice  of  Perimetry,  New  York,  1916. 


ABNORMALITIES    IN   THE    REFRACTION    OF   THE    ETE 


853 


emitted  by  an  object,  arc  always  i)rojcctcd  upon  the  blind  spot  of  one  eye,  this 
defect  is  ovcrconie  in  binocular  vision  by  the  fact  that  the  corrospondinK  raj's  in 
the  opposite  eye  are  focalized  outside  this  area  and  are  therefore  able  to  produce 
a  precise  and  complete  impression  in  consciousness. 

Since  the  sensitiveness  of  the  retina  diminishes  steadily  from  center  to  per- 
iphery and  also  shows  certain  minor  fluctuations  in  different  persons,  it  cannot 
surprise  us  to  find  that  the  visual  field  frequently  possesses  marked  irregularities. 
Furthermore,  it  must  be  evident  that  the  luminosity  and  color  of  an  object  have 
much  to  do  with  its  size,  because  a  white  disc  invariably  yields  a  larger  field  than 


06  L      081      0^^ 

Fig.  453. — Perimeter  Chart  to  Show  the  Field  of  Vision  for  a  Right  Eye  When 

Kept  in  a   Fixed   Position. 

one  poorly  illuminated  or  colored.  Consequently,  definite  conclusions  regarding 
abnormalities  of  the  visual  field  can  only  be  drawn  from  a  perimetric  chart 
which  has  been  obtained  under  test  conditions. 


CHAPTER  LXXIII 
ABNORMALITIES  IN  THE  REFRACTION  OF  THE  EYE 

Constant  Optical  Defects  of  the  Eye. — In  a  perfect  dioptric  system 
the  media  are  absolutely  transparent.  This  is  not  the  case  in  the 
hmnan  eye,  because  if  a  strong  beam  of  light  is  thrown  into  its  pupil, 
the  light  is  diffused  by  the  different  luminous  points  of  its  refractive 
media.  In  fact,  in  many  instances  true  opacities  may  be  detected 
which  are  dependent  upon  the  presence  of  formed  elements  within  the 


854  THE    SENSE    OF    SIGHT 

vitreous  humor.  In  order  to  render  the  latter  visible,  the  eye  should 
be  turned  upward  upon  a  uniformly  illuminated  surface,  when  they 
will  place  themselves  directly  in  the  line  of  vision,  and  give  rise  to  a 
sensation  of  beads,  strings  or  patches  floating  through  the  visual  field. 
On  account  of  their  almost  constant  motion,  which  may  be  increased 
by  movements  of  the  head  or  eyes,  they  are  known  as  the  muscce  voli- 
tantes.  They  are  said  to  represent  the  remains  of  the  embryonic  struc- 
ture of  the  vitreous  humor,  such  as  cells  which  have  failed  to  undergo 
a  complete  transformation  into  vitreous  substance.  These  fleeting 
visual  sensations  belong  to  the  group  of  the  ento'ptic  -phenomena,  be- 
cause they  are  produced  by  objects  within  the  eye. 

The  human  eye  also  shows  an  imperfect  centration  of  its  refractive 
media.  In  the  horizontal  meridian  the  optical  axis  of  the  cornea 
differs  from  that  of  the  lens  by  0.3°,  and  in  the  vertical  meridian  by 
as  much  as  1.3°.  Furthermore,  attention  has  already  been  called  to 
the  fact  that  the  optical  axis  of  the  eye  does  not  coincide  exactly  with 
the  visual  axis.  Naturally,  the  most  perfect  system  would  be  the  one 
in  which  the  refractive  media  are  accurately  centered  upon  an  axis 
which  strikes  the  retina  in  its  most  sensitive  area. 

Reference  has  already  been  made  to  the  fact  that  the  crystalline 
lens  is  not  free  from  spherical  aberration,  the  rays  passing  through 
its  peripheral  zone  being  converged  more  than  those  traversing  its 
center.  It  is  also  open  to  chromatic  aberration,  the  violet  rays  being 
brought  to  a  focus  in  a  point  closer  to  the  lens  than  the  red  rays.  Like 
in  all  optical  instruments,  these  aberrations  are  minimized  by  a  stop 
in  the  form  of  the  iris  which  shuts  out  its  marginal  zone.  In  spite 
of  this  fact,  however,  we  still  obtain  a  slight  spherical  aberration 
which,  together  with  the  imperfect  centration  of  the  refracting  media, 
gives  rise  to  a  mild  degree  of  astigmatism.  Thus,  a  star  or  the  light 
of  a  lantern  is  not  seen  as  a  round  luminous  point,  but  as  beset  with 
radial  streamers.  Quite  similarly,  the  chromatic  aberration  still 
remaining,  frequently  amounts  to  0.5  mm.  as  far  as  the  violet  and  red 
rays  are  concerned.  This  condition,  however,  does  not  interfere 
appreciably  with  the  clearness  of  the  retinal  image,  at  least,  not  with 
the  impression  produced  by  it  in  consciousness.  Admittedly,  the 
retina  becomes  abruptly  insensitive  toward  the  rays  at  the  extreme 
ends  of  the  spectrum,  and  is  more  readily  excited  by  the  rays  in  and 
near  the  yellow.  Consequently,  the  absence  of  chromatic  aberration 
in  our  eye  is  due  to  the  fact  that  the  iris  prevents  refraction  through  the 
peripheral  zone  of  the  lens,  and  secondly,  to  the  physiological  and  not 
to  the  optical  qualities  of  our  eye. 

Among  these  dioptric  defects  of  our  eye  might  also  be  mentioned 
the  entoptic  phenomena  produced  by  the  tears  anointing  the  anterior 
surface  of  the  cornea,  as  well  as  by  the  particles  of  mucus,  globules 
of  fat  and  dust  contained  therein.  The  latter  are  constantly  removed 
from  in  front  of  the  pupil  by  the  movements  of  the  eyelids.  Sub- 
jective visual  impressions  also  result  in  consequence  of  the  heterologous 


ABNORMALITIES    IN   THE    REFRACTION    OF   THE    EYE         855 

excitation  of  tho  retina  by  strong  pulsations  of  tlu;  retinal  blood-vessels, 
increased  intraocular  pressure,  and  venous  stagnation  caused,  for  ex- 
ample, by  the  acts  of  coughing  and  sneezing. 

Inconstant  Optical  Defects  of  the  Eye. — It  is  the  purpose  of  the 
normal  eve  to  bring  rays  of  light  lo  a  sharp  intersecting  point  upon 
the  retina.  An  eye  which  accomplishes  this  end,  is  said  to  be  em- 
metropic. This  condition  of  normal  refraction  is  designated  as 
emmetropia.  Conversely,  any  eye  which  is  not  capable  of  producing 
a  precise  focus,  is  said  to  be  ametropic.  This  condition  of  abnormal 
refraction  is  known  as  ametropia.  The  causes  underlying  the  latter 
may  be  arranged  in  the  following  order: 

(a)  Imperfect  curvature  of  the  cornea,  astigmatism. 
(6)    Diminished   elasticity   of   the    lens,    presbyopia, 
(c)   Imperfect  shape  of  the  eyeball. 

(1)  Myopia,  the  eyel)all  is  too  long. 

(2)  Hypermetropia,  the  eyeball  is  too  short. 

The  condition  of  presbyopia  has  been  fully  discussed  in  one  of  the  pre- 
ceding chapters  and  need  not  be  considered  again  at  this  time.  Fur- 
thermore, while  astigmatism  is  ascribed  in  this  outline  to  a  faulty 
curvature  of  the  cornea,  we  should  not  lose  sight  of  the  fact  that  this 
condition  may  also  be  caused  by  an  imperfect  curvature  of  the  lens; 
in  fact,  even  a  so-called  normal  eye  is  not  entirely  free  from  astigmatism, 
due  very  largely  to  an  improper  centration  of  the  constituents  of  the 
lens.  Regarding  the  exciting  causes  of  ametropia  no  perfectly  definite 
statements  can  be  made.  The  shape  of  the  eyeball  is  inherited  together 
with  other  biological  characteristics;  hence,  all  these  conditions  may 
be  entirely  beyond  our  power  of  preventing  them.  This  is  also  true 
of  those  defects  which  arise  later  on  in  life  in  consequence  of  retro- 
gressive changes,  such  as  infiltrations,  alterations  in  the  intraocular 
pressure,  and  senile  weaknesses  of  the  coats  of  the  eyeball.  In  the 
latter  case,  the  eyeball  becomes  more  pliable  and  adjusts  itself  more 
completely  to  the  shape  of  the  orbital  cavity.  In  spite  of  this  impor- 
tant element  of  inheritance,  however,  it  cannot  be  denied  that  these 
defects  may  also  be  acquired  in  consequence  of  an  improper  mode  of 
living,  and  erroneous  methods  in  the  use  of  the  eyes.  Thus,  the 
inhabitants  in  cities  are  constantly  subjected  to  near  work;  their  hori- 
zon being  limited  in  many  cases  by  the  walls  of  the  houses  on  the 
opposite  side  of  the  street.  Besides,  their  daily  work  requires  strong 
convergence  of  the  visual  axes  which  in  itself  heightens  the  intraocular 
pressure.  The  contrary  picture  is  presented  by  the  inhabitant  of  the 
open  country  whose  visual  impressions  are  in  large  part  received 
from  distances  greater  than  50  m.,  i.e.,  from  distances  which  require 
no  accommodation  at  all.  Civilization  imposes  upon  us  man}^  condi- 
tions which  can  only  be  met  by  carefully  following  the  most  fundamen- 
tal rules  regarding  physiological  optics. 

Astigmatism. — In  accordance  with  perfect  refraction,  the  cornea 
should  form  a  section  of  a  true  sphere,  but  this  is  not  always  the  case, 


856 


THE    SENSE    OF    SIGHT 


because  slight  differences  between  the  curvatures  of  its  vertical  and 
horizontal  meridians  are  not  uncommon.  Most  generally,  however, 
this  defect  is  overcome  functionally,  so  that  an  appreciable  disturbance 
in  vision  can  only  result  when  these  differences  exceed  a  certain  physio- 
logical limit.  Astigmatism  is  classified  as  regular  and  irregular,  the 
former  term  being  applied  to  it  when  the  meridian  of  maximal  curva- 
ture lies  at  right  angles  to  that  of  minimal  curvature.  Accordingly, 
irregular  astigmatism  may  be  defined  as  an  improper  curvature  of  the 
cornea  along  meridians  which  do  not  lie  at  right  angles  to  each  other. 
This  varietj'  is  most  commonly  produced  by  an  injury  and  subsequent 
formation  of  a  scar  ia  the  course  of  a  single  meridian;  hence,  it  is  re- 
stricted to  a  relatively'  narrow  region  of  the  cornea.  We  also  make  use 
of  the  terms  "with  the  rule"  and  "against  the  rule"  astigmatism.     The 


cSoO 


Fig.  454. — Diagram  to  Illustil^te  the  Corxza  of  the  Rays  ix  "with    the  Rrix" 

.\STIGSIATISiI. 

AB.  being  the  plane  of  greater  curvature,  its  rays  are  brought  to  a  focus  nearer  the 
lens  than  those  traversing  plane  CD. 


former  implies  that  the  cornea  is  more  highly  curved  along  its  vertical 
meridian,  while  the  latter  signifies  that  its  horizontal  curvature  is 
greater  than  its  vertical.  Ordinarily,  astigmatism  is  of  the  regular 
variety,  presenting  itself,  therefore,  as  an  excessive  curvature  along 
its  vertical  plane. 

The  functional  result  of  these  corneal  inequalities  is  not  difficult  to 
understand,  if  it  is  remembered  that  the  more  convex  surface  converges 
the  rays  of  light  more  strongly  than  the  less  convex  and  hence, 
focalizes  them  more  quickly  than  the  flatter  surface.  We  are  dealing 
here  with  planes,  i.e.,  with  linear  refraction  (Fig.  454).  Consequently', 
an  eye  which  has  been  rendered  ametropic  by  "with  the  rule"  astig- 
matism, converges  those  rays  of  light  in  a  greater  degree  which  traverse 
the  vertical  plane  of  its  cornea  (AB).  Although  the  lens  receives  these 
rays  in  a  more  convergent  form  than  those  which  have  passed  through 
the  horizontal  plane  of  the  cornea  (CB),  it  subjects  both  lines  of  light 


ABNORMALITIES    IN    THE    REFRACTION    OF    THE    EYE 


857 


rays  to  an  equal  degree  of  refraction.  Accordingly,  this  eye  obtains 
first  of  all  an  image  of  those  rays  which  have  traversed  the  more  highly 
curved  vertical  meridian  of  the  cornea  (AB)  and  lastly,  one  of  those 
rays  which  have  passed  through  its  relatively  flat  horizontal  plane 
(CD).  The  first  image  (ab)  must  necessarily  be  a  horizontal  line  and 
the  second  a  vertical  line  (cd).     In  between  these  two  images  are 


Fig.   455. — Astigmatic   Chakt.     (Howell.) 

situated  first  a  horizontal  ellipse,  then  a  circle  and  lastly,  a  vertical 
ellipse.  The  reason  for  this  is  that  the  rays  ab  again  diverge  distally 
to  the  horizontal  image  and  henceforth  intermingle  with  the  still 
convergent  rays  cd. 

To  illustrate,  let  us  fill  a  tall  beaker  with  water,  place  it  upon  a  table  and 
project  a  round  beam  of  light  through  its  central  area.     The  image  is  a  vertical 


Figs.  456,  457. — Lines   for  the  Detection  of  Astigmatism. 

line,  because  the  column  of  water  acts  in  the  manner  of  a  cylindrical  lens,  the  great- 
est convexity  of  which  is  adjusted  from  side  to  side.  If  this  beaker  is  now  held 
horizontally  so  that  its  greatest  convexity  hes  in  the  vertical  plane,  the  linear 
image  assumes  a  horizontal  position.  The  same  results  may  be  obtained  with  a 
cylindrical  lens.  By  means  of  two  equally  strong  cylindrical  lenses  superimposed 
upon  another  at  right  angles,  these  linear  lines  may  be  reconverted  into  a  rounded 
image. 


858 


THE    SENSE    OF    SIGHT 


The  presence  of  astigmatism  may  be  revealed  by  looking  at  a  chart 
such  as  is  represented  in  Fig.  455,  because  an  astigmatic  eye  is  unable 
simultaneously  to  obtain  a  perfectly  clear  image  of  lines  placed  at 
right  angles  to  one  another.  An  even  more  delicate  test  is  presented 
by  the  concentric  rings  reproduced  in  Fig.  456.  It  should  be  empha- 
sized, however,  that  the  oscillating  blurring  effect  which  one  frequently 
obtains  while  gazing  at  these  charts,  is  not  caused  by  an  astigmatic 
condition  of  the  refracting  media  of  the  eye,  but  by  slight  variations  in 
the  degree  of  contraction  of  the  ciliary  muscle.  Such  variations  must 
necessarily  give  rise  to  changes  in  the  accommodation. 


Fig.  458. — Ophthalmometer.     {Hardy.) 

An  instrument  which  enables  us  to  determine  the  direction  as  well  as  the  degree 
of  the  excessive  curvature  of  the  cornea,  is  the  ophthalmometer  of  Helmholtz  (Fig. 
458).  It  is  constructed  in  such  a  way  that  the  size  and  shape  of  the  corneal  image 
of  any  luminous  object  may  be  determined  with  absolute  accuracy.  Knowing  the 
size  of  this  object  and  its  distance  from  the  eye,  as  well  as  the  size  of  the  corneal 
reflection,  it  is  possible  to  ascertain  the  radius  of  curvature  of  the  cornea  according 


to  the  equation  r  = 


2-pi 
o-2i 


In  this  formula  p  represents  the  distance  of  the  object 


from  the  cornea,  o,  the  size  of  the  object,  and  ?,  the  size  of  the  corneal  image.  It 
need  scarcely  be  mentioned  that  the  reflecting  surface  and  telescope  of  this  instru- 
ment may  be  rotated  so  as  to  enable  the  observer  to  measure  the  curvature  of  the 
other  planes  of  the  cornea  and  to  compare  them  with  one  another.     In  the  modern 


ABNORMALITIES    IN    THE    HEFRACTION    OF    THE    EYE         859 

instruments  of  this  kind  tin;  Uiniinous  ol)j('ct,  or  tarfi;ct,  is  represented  by  a  doul)le 
figure  possessiufj;  ;i  sluirp  nuitlienuitical  outline,  which  in  turn  is  doubled  by  a  prism. 
The  four  inuiges  thus  obtained  are  first,  properly  adjusted  for  a  normal  cornea. 
When  transferred  upon  an  abnormally  curved  (!ornea,  this  defect  is  made  apparent 
immediately  by  their  displacement  toward  one  another. 

The  condition  of  astigmatism  may  be  corroctecl  in  one  of  two  ways: 
namely  (a)  by  diminishing  the  refraction  along  the  meridian  of  greatest 
curvature  or  (6)  by  increasing  the  refraction  along  the  meridian  of 
least  curvature.  Cylindrical  lenses  arc  used  for  this  purpose,  the 
refracting  power  of  which  compensates  precisely  for  the  unequal  cur- 
vature of  the  cornea.  In  the  former  case  we  employ  a  lens  designated 
as  minus  and,  in  the  latter,  one  designated  as  plus. 

Myopia. — The  condition  of  myopia  or  near-sightedness  is  due  either 
to  an  increase  in  the  longitudinal  diameter  of  the  eyeball,  or  to  an 
excessive  refracting  power  of  the  lens  and  other  media  of  the  eye.  In 
most  instances,  however,  it  is  attributable  to  the  former  cause. 

The  increase  in  the  length  of  the  eyeball  may  amount  to  a  fraction 
of  a  millimeter  or  to  as  much  as  3.8  mm.     Already  with  a  lengthening 


Fig.  459. — Diagram  to  Illustrate  the  Refraction  in  a  Myopic  Eye. 
L,  Luminous  point  focalized  in  L' in  the  vitreous  humor.     A  concave  lens L  renders 
these  rays  more  divergent  so  that  they  are  made  to  intersect  upon  the  retina  in  Z,^. 

of  0.16  mm.  the  far  point  is  moved  to  within  200  cm.  from  the  eye,  and 
with  an  increase  of  3.8  mm.  to  within  10  cm.  The  near  point  is  at 
this  time  only  5  to  6  cm.  distant.  Far  objects,  therefore,  cannot  be 
brought  to  a  focus  upon  the  retina,  unless  the  eye  is  equipped  with  an 
artificial  lens  which  exactly  compensates  for  this  defect.  Thus, 
parallel  rays  emerging  from  so  short  a  distance  as  6  m.,  actually  inter- 
sect in  the  vitreous  humor  in  front  of  the  retina.  Distally  to  this 
point  of  intersection,  the  rays  again  diverge  and  strike  the  retina  widely 
apart  as  a  dispersion  circle.  It  must  be  evident  that  this  condition 
cannot  be  improved  by  accommodating  more  sharply,  because  any 
increase  in  the  convexity  of  the  lens  must  move  the  focal  point  farther 
toward  the  lens,  and  give  rise  to  an  even  greater  dispersion  of  the 
retinal  image.  Quite  similarly,  it  may  be  reasoned  that  an  object 
held  very  close  to  the  eye,  is  in  a  much  better  position,  because  its 


860  THE    SENSE    OF    SIGHT 

divergent  rays  are  focalized  far  behind  the  lens  and  may,  therefore,  fall 
precisely  upon  the  retina  of  the  myopic  eye. 

In  order  to  enable  a  myopic  person  to  see  distant  objects  clearly, 
we  must  lessen  the  convergence  of  the  posterior  bundle  of  the  rays  of 
light,  i.e.,  we  must  force  their  focal  point  farther  backward  until  they 
reach  the  retina.  How  can  this  be  done?  By  rendering  the  enter- 
ing rays  more  divergent,  so  that  they  impinge  upon  the  lens  more 
widely  separated  from  one  another  than  formerly.  The  ordinary 
efforts  of  the  ciliary  muscle  will  then  suffice  to  centralize  these  more 
divergent  rays  precisely  upon  the  retina.  Consequently,  the  condition 
of  myopia  necessitates  the  use  of  concave  lenses  of  a  diverging  power 
exactly  proportional  to  the  degree  of  the  myopia  (Fig.  459). 

Hypermetropia. — The  condition  of  hypermetropia  or  far-sightedness 
is  due  either  to  a  decrease  in  the  longitudinal  diameter  of  the  ej^eball 
or  to  a  diminution  in  the  refracting  power  of  the  lens  and  other  media 
of  the  eye.  The  former  is  the  most  common  cause.  A  hypermetropic 
eye  is  unable  to  focalize  rays  emitted  bj^  near  objects,  because  its 
refractive  mechanism  is  not  sufficiently  powerful  to  .converge  these 
rays  in  a  way  to  bring  them  to  a  sharp  intersecting  point  upon  the 
retina.  Since  they  are  still  too  widely  separated  when  they  strike 
this  receptor,  they  cannot  give  a  clear  visual  impression.  In  the  more 
severe  cases,  this  statement  also  applies  to  the  parallel  rays,  so  that 
even  distant  objects  cannot  be  seen  distinctly  when  the  eye  is  at  rest. 
It  is  commonly  said,  that  the  focal  point  in  the  hypermetropic  eye  lies 
behind  the  retina,  but  naturally,  this  is  only  a  theoretical  possibility. 
With  the  increasing  hypermetropia,  the  near  point  constantly  moves 
farther  away  from  the  eye,  sometimes  as  far  as  200  cm.,  while  its  far 
point  lies  at  an  infinite  distance. 

It  will  be  seen,  therefore,  that  the  hypermetropic,  as  well  as  the 
myopic  eye,  when  at  rest,  sees  distant  objects  indistinctly.  Contrary  to 
the  myopic  eye,  however,  the  hypermetropic  organ  is  able  to  overcome 
this  difficulty  for  a  time  by  constantly  making  extra  efforts  at  accom- 
modation. It  is  evident  that  any  slight  shortening  of  the  eyeball 
may  be  compensated  for  by  rendering  the  lens  unusually  convex,  but 
naturally,  these  hyperefforts  must  fail  to  produce  the  desired  result  if 
the  shortening  has  progressed  beyond  the  limit  of  accommodation. 
Besides,  these  forceful  contractions  of  the  ciliary  muscle  are  generally 
followed  by  a  strained  feeling,  orbital  pain,  headache,  and  vertigo. 
Slight  degrees  of  hypermetropia,  however,  may  never  be  noticed  for 
the  reason  that  the  person  so  affected  may  readily  overcome  them 
by  a  somewhat  greater  contraction  of  the  ciliary  muscle.  In  the 
course  of  time,  this  muscle  then  frequently  undergoes  a  compen- 
satory hypertrophy. 

The  condition  of  hypermetropia  may  be  remedied  by  forcing  the 
focal  point  farther  toward  the  lens;  i.e.,  bj'  rendering  the  rays  of 
light  emerging  from  the  posterior  surface  of  the  lens,  more  convergent. 
How  can  this  end  be  accomplished?     By  supplying   the   lens  with 


ABNORMALITIES    IN    THE    REFRACTION    OF   THE    EYE         861 

convergent  rays  of  light,  but  since  there  are  no  convergent  rays  or- 
dinarily available  in  space,  this  direction  must  first  be  imparted 
to  the  parallel  and  divergent  rays  by  means  of  a  convex  lens  (Fig. 
460).  The  converging  power  of  the  lens  interposed  in  front  of  the 
eye,  must  be  proportional  to  the  degree  of  the  hypermetropia. 

Keeping  these  facts  clearly  in  mind,  it  will  be  seen  that  the  condi- 
tion of  presbyopia  developed  in  later  years,  must  improve  the  vision 
of  the  myopic  person,  but  diminish  that  of  the  hypermetropic.  Ob- 
viously, the  gradual  flattening  of  the  lens  in  consequence  of  the  effects 
of  old  age  reduces  its  refractive  power  and  forces  the  focal  point 
farther  backward.  If  the  eye  is  hypermetropic,  the  presbyopia 
makes  matters  worse,  because  it  tends  to  move  the  focal  point  still 
farther  *' behind"  the  retina.  In  the  myopic  eye,  on  the  other  hand, 
a  distinct  improvement  must  result,  because  the  presbyopic  lens  does 
not  converge  the  rays  so  strongly,   and  hence,   permits  their  focal 


Fig.  460. — Diagram  to  Illustrate  the  Refraction  in  a  Hypermetropic  Eye. 
L,  Luminous  point  focalized  in  L^  "behind"  the  retina.     A  convex  lens  C  renders 
these  rays  more  convergent  so  they  are  made  to  intersect  upon  the  retina  in  L^. 

point  to  move  closer  to  the  retina.  Conversely,  a  presbyopic  eye  may 
be  greatly  benefited  by  the  subsequent  development  of  a  myopia, 
because  the  recession  of  the  focal  point  is  then  compensated  for  by  a 
displacement  of  the  retina  in  a  backward  direction.  These  phenomena 
are  generally  designated  as  "second  sight." 

To  summarize:  An  emmetropic  eye  (Fig.  461,  E)  brings  parallel  and 
even  divergent  rays  of  light  to  a  sharp  focus  upon  the  retina,  while 
a  myopic  eye  (ilf )  focalizes  them  in  front  and  a  hypermetropic  eye, 
{H)  "behind"  the  retina.  In  order  to  render  M  emmetropic,  the 
entering  rays  of  light  must  be  diverged  by  means  of  a  concave  lens, 
while  H  can  only  be  made  emmetropic  by  converging  them  with  the 
aid  of  a  convex  lens. 

Simple  Methods  Used  to  Determine  the  Refractive  Power  of  the 
Eye. — The  acuity  of  vision  may  be  tested  in  different  rays.  Snel- 
len's test  types  consist  of  a  series  of  letters  placed  at  a  distance  of  5  m. 
from  the  eye.  It  has  been  determined  that  the  smallest  object  which 
a  normal  eye  is  capable  of  distinguishing  at  this  distance,  measures 


862 


THE    SENSE    OF    SIGHT 


1.454  mm.  and  that  lines  drawn  from  its  two  opposite  poles  through  the 
nodal  point  of  the  lens,  subtend  an  angle  of  60  degrees.  Consequently, 
any  other  two  luminous  points  separated  by  a  shorter  distance  than 


Fig.  461. — Diagram  to  Illustrate  the  Refraction  m  Emmetropia  and  Ametropia. 
E,  Emmetropic  eye  in  -which  luminous  point  L  is  brought  to  a  precise  focus  upon  the 
retina,  L^;  M,  myopic  eye  in  which  L  is  focalized  in  front  of  the  retina,  L';  H,  hyper- 
metropic eye  in  whichL  is  focalized  inL^  "behind"  the  retina.  In  M,  theuseof  a  concave 
lens  forces  Z,i  backward  upon  the  retina,  L*,  correcting  the  myopia,  whereas  in  H,  the 
use  of  a  convex  lens  forces  L'  forward  upon  the  retina,  L^. 

the  one  just  given,  are  no  longer  able  to  produce  distinct  impressions. 
At  this  distance,  the  retinal  image  measures  0.004  mm.,  which  corre- 
sponds to  a  visual  angle  of  60  seconds.     If  smaller  than  this,  the  two 


5m.         * 1^- 

Fig.  462. — Dlagr.au  to  Illustrate  the  Use  of  Sxellex's  Test  Types. 

focal  points  fail  to  give  separate  impressions,  because  they  fall  on  one 
and  the  same  cone.  At  a  distance  of  1  m.,  therefore,  an  object  would 
have  to  possess  a  dimension  of  one-fifth  of  1.454  mm.,  or  0.2908  mm., 


ABNORMALITIES    IX    THE    HEFUACTION    OF    THE    EYE         863 

in  order  to  subtond  an  anglo  of  GO  seconds.  Other  letters  may  then 
be  constructed  for  the  intervening  distances  by  simply  multiplying 
the  value  of  0.2908  mm.  by  the  distance  (F'ig.  462).  This  test,  there- 
fore, consists  in  determining  the  smallest  retinal  image,  corresponding 
to  a  visual  angle  of  GO  seconds,  which  an  eye  is  capable  of  perceiving. 
If  a  person  is  unable  to  recognize  this  test  type  when  held  at  its  proper 
distance,  he  is  first  made  to  look  at  it  through  a  weak  convex  lens.  If 
this  improves  his  vision,  he  is  hypermetropic,  because  only  an  eye  that 
is  too  short  or  possesses  a  subnormal  power  of  refraction,  is  in  a  position 
properly  to  focalize  convergent  rays.  He  should  be  given  the  strong- 
est convex  lens  with  w-hich  he  is  able  to  see  clearly,  because  clear  vision 
then  forces  him  to  relax  his  accommodation  as  much  as  possible.  If,  on 
the  other  hand,  the  vision  of  the  patient  is  more  highly  impaired  by 
the  interposition  of  convex  glasses,  he  is  myopic  and  requires  spectacles 
with  concave  lenses.  In  this  case,  the  lenses  prescribed  for  him,  should 
be  the  weakest  with  which  he  is  still  able  to  see  clearly,  because  this 
forces  him  to  bring  his  ciliary  mechanism  into  physiological  play.  It 
is  evident  that  this  test  should  also  be  made  separately  for  each  eye. 
Instead  of  the  test  letters,  ordinary  print  held  at  the  proper  reading 
distance,  may  be  used. 

The  Ophthalmoscopic  Method. — The  eye  is  a  camera  obscura,  and 
its  interior  is  not  open  to  direct  inspection,  because  the  choroid  and  iris 
are  pigmented  and  practically  impermeable  to  light.  Even  in  the 
albino,  nothing  more  than  a  slight  "reflex"  sensation  of  pink  is  ob- 
tained. The  fundus  of  the  eye  also  remains  absolutely  invisible  if  we 
look  through  the  pupillar  orifice,  because  we  must  then  assume  a  posi- 
tion directly  in  front  of  the  head  of  the  observed  person.  Obviously, 
the  rays  of  light  are  thereby  prevented  from  entering  the  vitreous 
chamber.  In  some  animals,  however,  the  visual  axes  are  more  diver- 
gent so  that  the  rays  can  get  past  the  observer's  head  to  illuminate  the 
retina. 

Whenever  light  is  reflected  into  an  eye,  a  large  part  of  it  is  absorbed 
by  the  pigment  of  the  choroid,  w^hile  a  small  portion  of  it  is  refracted 
outward  into  space  in  the  same  direction  in  which  it  entered.  It 
must  be  evident  that  if  a  luminous  point  in  space  L  is  accurately  cen- 
tered upon  the  retina  in  L',  this  focal  point  L'  remits  divergent  rays 
which  are  again  rendered  convergent  by  the  lens  to  be  intersected  in  L. 
Consequentl}',  L  and  L'  are  conjugate  foci.  This  outward  refraction 
is  made  impossible  if  we  adjust  our  eyes  to  look  into  the  pupillar  orifice 
of  the  patient,  because  we  thereby  cut  off  the  supply  of  light  rays  and 
render  the  retina  non-luminous.  In  1851  Helmholtz  conceived  the 
idea  of  illuminating  the  eye  from  a  lateral  source  of  light  by  means  of 
three  mirrors  placed  at  an  angle  of  56°  to  the  line  of  Ught.  This  instru- 
ment which  he  called  the  ophthahnoscope  (Fig.  463),  has  been  modified 
repeatedly,  but  the  principle  involved  in  its  construction  has  remained 
the  same.  In  its  modern  form  it  consists  of  a  concave  silvered  mirror 
by  means  of  which  light  is  reflected  into  the  patient's  eye  from  a  gas- 


864  THE    SENSE    OF   SIGHT 

lamp  adjusted  laterally  to  his  head.  Since  the  constriction  of  the 
iris  would  seriously  interfere  with  this  examination,  this  mechanism 
is  temporarily  paralyzed  by  means  of  atropin.  Some  mirrors  are 
equipped  with  a  small  electric  lamp  (Dennett's  or  Marple's  modifica- 
tion) which  enables  us  to  examine  the  eyes  of  bedridden  patients  and 
also  obviates  in  a  measure  the  use  of  atropine.  *     In  the  center  of  the 


Fig.  463. — Loring's  Ophthalmoscope,  with  Tilting  Mieror,  Complete  Disc  of 
Lenses  from  —  1  to  —  8  and  0  to  +7,  and  Supplemental  Quadrant  Containing  + 
0.5  AND  +  16  D.     This  Affords  66  Glasses  or  Combinations  from  +  23  to   —  24   D. 

reflecting  mirror  is  a  small  opening  which  is  adjusted  directly  in  front 
of  the  pupil  of  the  observer's  eye.  We  may  then  follow  either  the 
direct  or  the  indirect  method  of  ophthalmoscopic  examination. 

The  Direct  Method. — If  the  eye  of  the  observer  is  not  emmetropic,  it  should 
first  be  made  so  by  spectacles  (Fig.  464).  The  mirror  (m)  is  held  close  to  the  ob- 
served eye,  so  that  the  rays  reflected  from  it  are  able  to  spread  out  widely  upon  the 
opposing  retina  {A'B').  The  area  of  the  retina  so  illuminated  remits  ra.vs  (L) 
which  traverse  the  dioptric  media  of  this  eye  and  are  sent  outward  into  space. 
Now,  it  is  evident  that  the  emmetropic  eye  remits  these  rays  parallel  to  the  visual 

^  Large  ophthalmoscopes  have  been  constructed  by  Gullstrand  and  others. 
The  first  gives  a  magnification  of  5  to  50  times  in  monocular  and  20  times  in 
binocular  vision.  Hertzell  illuminates  the  eye  by  means  of  an  80  candle  power 
electric  lamp  placed  in  the  patient's  mouth  (ophthalmodiaphanoscopy). 


ABNORMALITIES    IN    THE    UKFIIACTION    OF    TIIK    KVK 


SG5 


axis,  while  (lie  myopic  and  hypermetropic  eyes  refract  them  outward  in  an  ol)Uque 
direction.  Assuming  then  that  tlie  observed  person  is  emmetropic  and  is  accom- 
mochitinfj;  for  a  fur  object,  tiie  parallel  rays  emitted  by  his  retina  must  traverse  the 
central  orihce  in  the  mirror  anil  be  l)rounht  to  a  jjrecise  focus  u])on  the  retina  of  the 
observer(Li).  The  latter  thus  obtains  an  erect  niannified  imanc'  of  t  lu;  nitina  of  the 
observed  person.  A  clear  inuise,  however,  can  only  be  obtained  if  both  eyes  are 
emmetropic  and  are  accommodated  for  the  distance.  Some  difliculty  may  be 
experienced  at  first  in  relaxinp;  the  accommodation,  but  this  may  be  overcome  if 
one  imagines  himself  stizinfj;  at  an  ol),iect  phiced  far  behind  the  eye  of  the  patient. 
A  complete  relaxation  of  the  eye  of  tlie  observed  person  is  usually  secured  by  the 
administration  of  atropine,  which  alkaloid  temporarily  j)aralyzes  the  ciliary 
mechanism.  It  also  dilates  the  i)upil,  thereby  preventiiifz;  any  interference  on  the 
part  of  the  iris  with  the  reflection  and  refraction  of  the  liyht. 

If  the  observed  eye  is  myopic,^  the  rays  of  lipiht  emitted  by  the  ilhmiinated  area 
of  its  retina,  are  refracted  into  space  as  a  converfj;ent  beam  and  (!annot,  th(>reforc, 
be  focalized  by  the  emmetropic  and  relaxed  eye  of  the  observer  (Fig.  465).     In 


Kd 


%-'■ 


Fig.  464. — Direct    Ophtilvlmoscopy. 
Diagram    to  illustrate  the  remittance  of  the  rays  of  light  by  an  emmetropic  eye. 
O,   observer's  eye;  M,  mirror;  P,  patient's  eye;  F,  the  rays  FA  and  FB,  illumiiuite  the 
retina  of  P  by  a  diffusion  circle  ^'B';  L,  the  rays  emitted  by  this  luminous  point  are 
brought  to  a  precise  focus  in  L'  of  the  observer's  retina. 

order  to  bring  these  rays  to  a  precise  focus,  they  must  first  be  rendered  less  conver- 
gent by  the  interposition  of  a  biconcave  lens  of  sufKcient  diverging  power  to  over- 
come their  excessive  convergence.  If  the  observed  eye  is  hypermetropic  (Fig. 
466),  the  rays  emitted  by  its  illuminated  retina,  are  divergent  and  cannot,  there- 
fore, enter  the  pupil  of  the  observe^.  They  may  be  made  to  do  so,  however,  by 
placing  a  biconvex  lens  in  front  of  the  orifice  in  the  reflecting  mirror.  The  strength 
of  the  latter  should  be  such  that  the  formerly  divergent  rays  now  intersect  in  the 
retina  of  the  relaxed  emmetropic  ej-e  of  the  observer. 

This  method  not  only  allows  us  to  detect  errors  of  refraction,  but  also  to  deter- 
mine the  strength  of  the  lens  which  must  be  used  by  the  patient  in  order  to  render 
him  emmetropic.  Clearly,  the  strength  and  sign  of  the  lens  needed  by  him  to 
correct  his  defect,  is  indicated  by  the  lens  which  the  observer  must  employ  in  order 
to  obtain  a  clear  image  of  his  retina.  For  reasons  stated  previously,  the  weakest 
concave  lens  should  be  prescribed  for  myopia  and  the  strongest  convex  lens  for 

^  If  the  observer  moves  his  head  and  ophthalmoscope  from  side  to  side,  the 
retinal  vessels  will  appear  to  move  in  the  same  direction  in  the  hypermetropic  and 
in  the  opposite  direction  in  the  myopic  eye. 

55 


866 


THE    SENSE    OF    SIGHT 


hypermetropia.i  Astigmatism  may  also  be  detected  and  corrected  in  this  way. 
In  order  to  form  an  idea  regarding  the  meridians  in  which  the  refraction  is  defect- 
ive, we  only  need  to  observe  the  retinal  blood-vessels  along  the  horizontal  and 


Fig.  465. — Direct  Ophthalmoscopy. 
Diagram  to  illustrate  the  remittance  of  the  rays  of  light  by  the  mj-opic  eye.  O, 
observer's  eye;  M,  mirror;  P,  patient's  eye;  F,  the  rays  FA  and  FB  illuminate  the 
retina  of  P  bj*  a  diffusion  circle  A^  B^;L,  the  rays  emitted  by  this  luminous  point  leave 
the  eye  of  P  convergently  and  must  therefore  be  rendered  divergent  by  the  interposition 
of  a  concave  lens  before  they  can  be  focalized  inL^  by  the  eye  of  the  observer. 

vertical  planes  of  the  optic  disc  (Fig.  438).  The  latter  appears  as  a  nearly  round 
or  slightly  oval  area  varying  in  color  from  grayish  pink  to  a  more  decided  red.  Its 
center  is  occupied  by  a  light  patch  marking  more  e.xactly  the  entrance  of  the 
retinal  blood-vessels.     The  circumference  of  the  optic  papilla  appears  as  a  dark, 


Fig.  466. — DnizcT  Ophthalmoscopy. 
Diagram  to  illustrate  the  remittance  of  the  rays  of  light  by  the  h>-permetropic  eye. 
O,  observer's  eye;  M,  mirror  ;P,  patient's  eye ;F.  the  raysF.4  andFB,  illuminate  the  retina 
of  P  by  a  diffusion  circle  AW^;L.  the  rays  emitted  by  this  luminous  point  leave  the  eye 
of  P  divergently  and  must  therefore  be  rendered  convergent  by  the  interposition  of  a 
convex  lens  before  they  can  be  focalized  in  L'  of  the  eye  of  the  observer. 


usually  incomplete  ring  representing  the  border  of  the  choroid  coat.     Within  this 
lies  a  faint  white  line,  indicative  of  the  brim  of  the  sclerotic  coat. 

1  If  the  observer  is  ametropic  and  does  not  emploj'  the  necessary  glasses  during 
this  examination,  he  must  of  course  make  this  additional  correction. 


ABNORMALITIES    IN    THE    REFRACTION    OF   THE    EYE         867 

The  Indirect  Method. — As  the  name  indicates,  indirect  ophthalmoscopy  con- 
sists in  the  formation  of  a  retinal  image  in  space  in  front  of  the  observer's  eye,  the 
principle  involved  being  similar  to  that  of  the  compound  microscope  (Fig.  407). 
The  reflecting  mirror  is  held  at  about  an  arm's  length  from  the  observed  eye  (30 
cm.).  A  convex  lens  of  aiiout  20  diopters  is  then  placed  clo.se  to  the  latter.  Ob- 
viously, the  purpo.se  of  this  lens  is  to  gather  the  rays  emerging  from  the  observed 
eye  and  to  bring  them  to  a  focus  between  it  and  the  ob.server's  eye.  This  real 
inverted  image  hi  space  is  regarded  by  the  observer  through  a  lens  of  about  5 
diopters  in.serted  in  the  orifice  of  the  ophllialmo.scope.  To  .see  this  image  dearly, 
the  emmetropic  observer  must  move  nearer  to  or  farther  away  from  the  patient's 
eye  until  his  distance  equals  the  focal  distance  of  this  lens,  viz. :  20  cm.  Errors  in 
refraction  may  be  detected  by  moving  the  o})jective  lens  of  20  diopters  farther 
away  from  the  eye,  the  image  then  becoming  larger  in  myopia  and  smaller  in  hyper- 
metropia.  The  observer  then  interposes  different  concave  (  — )  and  convex  (-|-) 
lenses  until  the  image  becomes  perfectlj''  clear. 


o  m 

Fig.  467. — Indirect  Ophthalmoscopy. 
Diagram  to  illu.strate  the  remittance  of  the  rays  of  light  by  an  emmetropic  eye. 
O,  observer's  eye;  M,  mirror;  P,  patient's  eye;  F,  the  rays  FA  and  FB  illuminate  the 
retina  of  P  by  a  diffusion  circle  A^B^  (inverted  in  this  case)  L,  the  rays  emitted  by  these 
luminous  points  are  converted  into  a  real  inverted  image  in  the  air  at  /.  The  latter  is 
then  focused  upon  the  observer's  retina. 

Skiascopy  or  the  Shadow  Test  (Retinoscopy). — This  method  con- 
sists in  determining  the  direction  of  the  movement  of  the  hght  in  the 
pupillar  orifice  when  it  is  made  to  move  back  and  forth  by  rotating 
the  reflecting  mirror  around  the  long  axis  of  the  handle  supporting 
it.  It  is  a  matter  of  common  observation  that  a  beam  of  light  reflected 
against  a  wall,  moves  with  the  reflecting  mirror.  A  similar  phenome- 
non occurs  in  the  human  eye  if  the  retina  is  illuminated  so  that  it 
can  emit  light.  Thus,  if  a  beam  of  hght  is  thrown  into  the  eye,  the 
pupil  is  completely  illuminated.  If  the  mirror  is  now  rotated  around 
its  long  axis,  the  pupil  is  darkened  on  one  side  and  this  shadow  moves 
either  in  the  same  or  in  the  opposite  direction  to  the  rotation  according 
to  the  position  of  the  observer's  eye  in  the  line  of  vision  of  the  observed 
eye  (Fig.  468).  If  situated  exactly  at  its  far  point,  the  pupil  remains 
either  dark  or  is  fully  illuminated  and  does  not  exhibit  a  distinct 
moving  shadow.  This  point  indicates  the  position  of  the  so-called 
point  oj  reversal  (A).  Retinoscopy,  therefore,  is  a  method  by  means  of 
which  the  distance  of  this  point  may  be  accurately  determined.     Be- 


868  THE    SENSE    OF    SIGHT 

yond  this  point  (B)  an  inverted  image  will  be  obtained,  and  the  light 
in  the  pupil  will  appear  to  move  against  the  rotation  of  the  mirror, 
whereas  inside  A  the  image  (C)  is  erect,  and  the  light  seems  to  move 
with  the  rotation. 

In  myopia,  the  point  of  reversal  lies  close  to  the  eye.  Con- 
sequently, if  the  observer  finds  that,  on  throwing  light  into  the  eye, 
the  light  in  the  pupil  is  against  the  rotation,  he  must  be  beyond  the 
point  of  reversal.     He  should  then  approach  the  observed  eye  slowly 


Fig.  468. — Diagram  to  Illustrate  the  Location  of  the  Point  of  Reversal  as  Ob- 
tained BY  the  Sh.\dow  Test. 

until  he  finds  this  movement  to  be  with  the  rotation.  These  obser- 
vations should  be  repeated  until  this  point  has  been  accurately  local- 
ized. The  distance  between  this  point  and  the  eye  should  then  be 
measured  with  the  ruler,  because  it  represents  the  focal  distance  of 
the  lens  necessary  to  correct  the  myopia.  Thus,  if  it  is  possible 
to  obtain  an  erect  movement  at  a  point  55  cm.  from  the  eye  and  a 
reversed  movement  at  80  cm.,  the  exact  point  of  reversal  will  be  at 
67  cm.     The  myopia  equals  in  this  case  1.50  D. 


Fig.  469. — Diagram  to  Illustr.\te  the  Location  of  the  Point  of  Reversal  as  Ob- 
tained  BT   THE    SH-VDOW   TeST   IN   THE    HYPERMETROPIC   EtE. 

In  hypermetropia  the  rays  are  emitted  divergently  and  hence,  a 
point  of  reversal  cannot  be  present.  The  observer  then  finds  that  the 
movement  of  the  light  remains  with  the  rotation,  no  matter  how  far  he 
withdraws  from  the  eye.  A  convex  lens  should  now  be  interposed  to 
form  a  point  of  reversal  at  a  convenient  distance  from  it,  thereby  ren- 
dering it  artificalty  myopic  (Fig.  469).  This  point  of  reversal  having 
been  ascertained  with  the  ruler,  the  degree  of  myopia  represented  by  it 
is  then  subtracted  from  the  total  strength  of  this  lens.     The  remainder 


BINOCULAR   VISION  869 

corresponds  to  the  power  which  is  required  to  correct  the  divergence 
of  the  rays,  i.e.,  the  hypermetropia.  Thus,  if  a  lens  of  5D  is  employed 
and  the  movement  of  the  light  remains  with  the  rotation  of  the  mirror 
until  a  little  within  a  distance  of  1  m.  but  is  reversed  at  a  distance  of  a 
little  more  than  1  m.,  the  point  of  reversal  is  at  1  m.  Consequently, 
ID  of  the  strength  of  this  lens  is  required  to  converge  the  rays, 
while  4D  of  the  total  5D  have  been  made  use  of  in  overcoming  the 
divergency  of  the  rays  upon  their  projection  from  the  observed  eye. 
In  this  case,  the  hypermetropia  equals  4D, 

In  astigmatism  the  same  method  may  be  followed,  but  these 
tests  must  then  be  repeated  for  different  meridians,  i.e.,  the  point 
of  reversal  must  be  ascertained  separately  for  the  horizontal,  vertical 
and  oblique  planes. 


CHAPTER  LXXIV 
BINOCULAR  VISION 

The  Movements  of  the  Eyeballs. — The  organ  of  vision  consists 
of  the  globe  of  the  eye,  measuring  nearly  an  inch  from  side  to  side, 
slightly  less  than  an  inch  from  above  downward  and  somewhat 
more  than  an  inch  from  before  backward.  Its  volume  equals  6.5 
cm.  and  its  weight  nearly  7  grams.  Connected  with  it  externally 
are  different  muscles,  nerves  and  blood-vessels.  It  is  supported  by  a 
quantity  of  fat  and  connective  tissue,  the  latter  forming  a  lymphatic 
space  known  as  the  capsule  of  Tenon.  Within  this  capsule  the  eyeball 
is  made  to  move  by  the  contraction  of  a  set  of  muscles,  designated  as  the 
ocular  muscles.  These  are  the  four  recti  and  two  obhque  muscles. 
The  former,  which  are  known  respectively  as  the  superior,  inferior, 
external  and  internal,  take  their  origin  from  a  tendinous  ring  investing 
the  optic  foramen  and  sphenoidal  fissure.  From  here  they  pass 
forward  along  the  walls  of  the  orbital  cavity  and  finally  perforate 
the  aforesaid  lymphatic  space  to  gain  access  to  the  equatorial  region 
of  the  eyeball.  Closely  investing  the  latter,  they  finally  terminate 
in  their  respective  positions  about  7  mm.  posterior  to  the  margin  of 
the  cornea.  The  superior  oblique  muscle  arises  from  a  small  tendon 
upon  the  inner  margin  of  the  optic  foramen  and,  passing  forward  to 
the  inner  angle  of  the  orbit,  terminates  in  a  rounded  tendon  which 
plays  in  a  pulley  of  fibro-cartilaginous  tissue  suspended  from  the 
depression  in  the  internal  angular  process  of  the  frontal  bone.  From 
here  this  tendon  is  reflected  backward,  outward  and  downward  upon 
the  outer  part  of  the  ej^eball  about  midway  between  its  cornea  and  the 
entrance  of  the  optic  nerve.  The  inferior  oblique  muscle  arises  from  a 
depression  in  the  orbital  plate  of  the  superior  maxillary  bone,  external 


870 


THE    SENSE    OF    SIGHT 


to  the  lacrimal  groove.  From  here  it  passes  outward,  upward  and 
backward,  and  finally  ends  in  a  tendinous  expansion  which  is  inserted 
in  the  sclera  upon  the  outer  part  of  the  eyeball,  near  to  but  somewhat 
behind  the  tendon  of  the  superior  oblique. 

The  movements  of  the  eyeball  are  similar  to  those  of  the  head  of  a 
long  bone  within  its  socket,  an  unrestricted  motion  being  made  im- 
possible by  several  resistances,  such  as  the  insertion  of  the  different 
muscles,  the  capsular  aponeurosis  and  the  entrance  of  the  optic  nerve. 
The  recti  muscles  act  antagonistic  to  one  another,  the  range  of  con- 


II 


IV 


Fig.  470. — Diagram  Showing  the  Lines  of  Insertion  of  the  Ocular  Muscles  into  the 
Sclerotic.      (Alerkel   and   Kallins.) 
I,  Globe  from  above;  II,  from  the  nasal  side;  III,  from  below;  IV,  from  the  temporal 
side,     s,  rectus  superior;  i,  rectus  inferior;  m,  rectus  internus  (s.  mesialis) ;  e,  rectus 
externus  (s.  lateralis);  os,  obliquus  superior;  oi,  obliquus  inferior. 


traction  of  one  being  restricted  by  the  extension  of  the  opposite  one. 
Their  action,  however,  is  unable  to  pull  the  eyeball  backward  owing 
to  the  antagonistic  action  of  the  smooth  musculature  of  Tenon's 
capsule.  In  some  animals,  such  as  the  reptilia  and  amphibia  and 
several  mammals,  a  movement  of  this  kind  is  effected  by  a  special 
muscle  known  as  the  retractor  bulbi. 

The  globe  of  the  eye  does  not  alter  its  position  in  rotating,  but  is 
merely  turned  around  its  axes.  Thus,  if  it  stated  that  the  eye  is  moved 
upward,  reference  is  had  merely  to  the  relative  position  of  its  anterior 
and  posterior  poles.  While  the  cornea  moves  upward,  the  back  of  the 
eyeball  moves  downward,  and  vice  versa.  Although  the  axes  around 
which  the  eye  may  be  rotated  are  many,  it  is  customary  to  recognize 


BINOCULAR   VISION 


871 


oSZ.sup. 


obt-  Slip. 


three  principal  ones,  namely,  two  horizontal  and  one  vertical.  All  three 
traverse  the  center  of  rotation  at  right  angles  to  one  another,  allowing 
the  following  movements  of  the  eye  to  be  executed:  (a)  outward  or 
inward  around  its  vertical  axis,  giving  rise  to  its  average  abduction 
or  adduction,  (6)  upward  or  downward  around  its  transverse  hori- 
zontal axis,  and  (c)  around  its  sagittal  axis  connecting  its  anterior 
and  posterior  poles.  The  only  movements  carried  on  by  the  contraction 
of  one  muscle,  or  rather,  by  the  reciprocal  action  of  a  single  pair  of 
muscles,  are  abduction  and  adduction.  The  former  is  accomplished  by 
the  external  rectus  and  the  latter,  by  the  internal  rectus.  Movements 
upward  or  downward  necessitate  the  contraction  of  at  least  two 
muscles,  the  former  being  mediated  by 
the  superior  rectus  and  inferior  oblique, 
and  the  latter  ])y  the  inferior  rectus 
and  superior  oblique.  When  acting 
singly,  the  superior  rectus  draws  the 
cornea  upward  and  inward.  This  ac- 
tion is  combined  with  that  of  the  in- 
ferior oblique  which  draws  it  upward 
and  outward,  but  would  also,  theoret- 
ically considered,  rotate  the  eyeball 
outward  around  its  sagittal  axis.  Quite 
similarly,  the  inferior  rectus,  when 
acting  alone,  pulls  the  cornea  down- 
ward, but  also  adducts  it  and  should 
rotate  it  outward.  The  superior  ob- 
lique, on  the  other  hand,  deviates  the 
cornea  downward  and  slightly  outward, 
but  should  also  turn  it  inward. 

It  should  be  emphasized,  however. 


r.int 


r.ext. 


T.sup.  r.wt 


Fig.    471. — Diagram    to    Show 


that  a  rotation  of  the  eyeball  around  Points  of  Attachment  and  Lines  of 
•-„ i      ^ ,      •  -1  J-  4-    1        Action  of  Extrinsic  Ocular    Mts- 

Its  antero-posterior  axis  does  not  take  ^^^     (^landois.) 
place    under    ordinary    conditions, 

although  the  course  of  these  four  muscles  might  warrant  us  to  as- 
sume such  an  action.  This  point  may  be  proved  by  first  gazing  at 
the  vertical  filaments  of  an  electric  lamp  and  then  resting  the  eyes 
upon  a  uniform  gray  surface.  The  after-image  of  these  luminous 
lines  which  will  then  be  formed,  shows  them  in  their  original  vertical 
position  no  matter  whether  the  eye  be  turned  upward,  downward 
or  in  an  oblique  direction.  Naturally,  if  the  eye  were  actually 
turned  around  its  antero-posterior  axis,  the  after-image  of  these 
filaments  should  really  assume  a  slanting  position.  Movements  of 
the  eyeballs  around  oblique  axes  require  the  cooperation  of  three 
muscles,  viz.: 

(a)  Upward  and  outward;  superior  rectus,  inferior  oblique  and 
external  rectus. 


872 


THE    SENSE    OF    SIGHT 


(b)  Upward  and  inward;  superior  rectus,  inferior  oblique  and  inter- 
nal rectus. 

(c)  Downward  and  outward;  inferior  rectus,  superior  oblique 
and  external  rectus. 

{d)  Downward  and  inward;  inferior  rectus,  superior  oblique  and 
internal  rectus. 

Binocular  Vision. — In  man  the  movements  of  the  eyes  are  bilateral, 
each  eye  being  moved  around  its  center  of  rotation,  situated  13.5  mm. 
behind  the  cornea  or  1.3  mm.  behind  the  middle  of  the  eyeball.  When 
the  head  is  held  erect  and  the  eyes  are  directed  to  a  point  at  the  horizon, 
their  visual  axes  are  parallel  to  one  another.  This  constitutes  the 
primary  position.  Wlien  the  eyes  are  moved  directly  upward,  down- 
ward, outward  or  inward,  they  occupj^  secondary  positions  and  when 
turned  in  obhque  directions,  tertiary  positions.  The  movements  of 
the  two  eyes  are  correlated  by  a  central  mass  of  gray  matter,^  the 


J  ^ 

Fig.  472. — Dl^grams  to  Show  Homoxymols  and  HEXEROXTiious  Diplopia. 
In  I  the  eyes  are  focused  on  A;  the  images  of  B  fall  on  non-corresponding  points, 
— that  is,  on  different  sides  of  the  fovese,  and  are  seen  double,  being  projected  to  the 
plane  of  A,  giving  heteronymous  diplopia.  In  //  the  eyes  are  focused  on  the  nearer 
point.  A,  and  the  farther  point,  B,  forms  images  on  non-corresponding  points  and 
is  seen  double — homonymous  diplopia — the  images  being  projected  to  the  focal 
plane  A. 

anatomical  basis  for  the  bilateral  character  of  their  innervation  being 
furnished  by  the  fact  that  each  oculomotor  nerve  is  composed  of 
fibers  derived  from  both  nuclei  and  that  the  latter  are '  intimately 
connected  with  one  another  b}'  commissural  fibers.  Two  chief  types 
of  movements  may  be  recognized,  namely: 

(a)  Movements  during  which  the  visual  axes  of  the  eyes  are  kept  practicallj^ 
parallel  to  one  another,  no  matter  whether  they  are  deviated  along  the  vertical 
plane  of  the  visual  field  or  laterally  outward.  Naturally,  this  parallelism  can  only 
be  mamtained  if  the  object  remains  at  some  distance  from  the  eyes. 

(6)  Movements  during  which  the  visual  axes  are  converged  in  order  to  be  able 
to  observe  objects  near  the  eyes.  This  convergence  results  invariably  during  near 
\'ision  and  is  therefore  accompanied  b}'  the  contraction  of  the  ciliary  muscle. 

Converging  movements  of  the  ej^eballs  directed  at  objects  situated 
laterally  from  us,  may  also  be  executed,  but  since  these  require  an 

^  Hering's  Law  of  Uniform  Inneryation,  Hermann's  Handb.  der  Physiol.,  1879, 
in,  343.  • 


BINOCULAR   VISION  873 

extra  effort,  they  are  usually  supplemented  by  movements  of  the  head 
as  a  whole.  This  furnishes  a  much  simpler  means  of  bringing  the 
object  into  direct  opposition  with  the  yellow  spots.  Furthermore,  it  will 
be  noted  that  the  convergence  of  the  eyes  necessitates  a  symmetrical 
innervation  of  the  internal  recti  muscles,  while  a  symmetrical  in- 
nervation of  the  external  recti  is  quite  superfluous,  because  we  do 
not  diverge  the  visual  axes  during  normal  vision.  In  fact,  a  move- 
ment of  this  kind  would  give  rise  to  the  condition  of  diplopia  or  double 
vision,  for  the  obvious  reason  that  the  rays  of  light  would  then  be 
made  to  fall  upon  areas  of  the  retina  which  are  not  psychically  cor- 
related. A  condition  of  diplopia,  however,  may  be  established  without 
much  difficulty  by  exerting  a  gentle  pressure  upon  one  eyeball,  so  that 
it  is  momentarily  forced  out  of  its  normal  position.  Since  the  retinae 
of  the  two  eyes  are  then  activated  in  dissimilar  areas,  a  double  im- 
pression in  consciousness  is  the  natural  consequence. 

Diplopia  is  a  common  symptom  of  certain  disorders  of  the  nervous 
sj'stem,  leading  to  disturbances  in  the  coordinated  action  of  the 
different  orbital  muscles.  It  is  true,  however,  that  slight  divergencies 
are  generally  compensated  for  volitionally  by  simply  causing  the 
weaker  muscle  to  contract  more  forcibly  than  it  would  otherwise,  but 
naturally,  a  point  will  eventually  be  reached  when  these  extra  efforts 
cease  to  produce  the  desired  effect.  A  condition  characterized  by  a 
partial  loss  of  balance  of  the  eye  muscles,  is  designated  as  heterophoria, 
and  one  characterized  by  a  more  complete  loss,  as  strabismus  or  squint. 
In  the  latter  case,  the  person  is  quite  unable  to  direct  the  visual  axes 
jointly  upon  the  object,  but  double  vision  need  not  result  even  then, 
unless  the  strabismus  is  very  pronounced  or  has  arisen  very  suddenly  in 
consequence  of  some  injury.  Most  generally,  the  patient  learns  by 
experience  to  base  his  visual  associations  upon  the  impressions  derived 
from  the  more  normal  eye,  and  ignores  or  suppresses  the  image  from 
the  non-corresponding  area  of  the  opposite  retina.  Heterophoria, 
as  well  as  strabismus,  may  be  mitigated  or  remedied  altogether  by  the 
use  of  prisms. 

This  discussion  shows  that  single  vision  with  the  two  eyes  is  due  to 
a  fusion  of  the  visual  impressions  in  consciousness,  and  is  largely  the 
result  of  experience.  Thus,  we  speak  of  "corresponding  points" 
upon  the  retina,  although  it  must  be  evident  that  a  certain  cone  in  one 
retina  cannot  act  in  unison  with  a  cone  occupying  the  same  position 
in  the  opposite  retina.  The  aforesaid  term,  therefore,  is  not  indicative 
of  a  histological  identity,  but  of  an  identity  in  function.  Consequently, 
while  certain  areas  in  the  two  retinae  may  be  correlated  functionally, 
they  are  not  symmetrically  placed.  This  fusion  of  the  visual  impres- 
sions in   consciousness   may   be   illustrated   in   the   following   wa3's: 

(a)  If  the  right  eye  is  made  to  receive  a  certain  impression  of  red  and  the  left 
eye,  an  identical  impression  of  blue,  the  result  is  either  a  fusion  of  the  two  colored 
fields  (purple)  or  a  struggle  of  the  two  fields  for  supremac}'.  In  the  latter  case,  a 
sensation  of  red  alternates  with  a  sensation  of  blue. 


874  THE    SENSE    OF    SIGHT 

(6)  If  the  right  eye  is  made  to  receive  a  figure  composed  of  horizontal  lines  and 
the  left  eye  one  composed  of  vertical  lines,  the  result  is  a  struggle  between  these 
impressions.  Sometimes  the  former  and  sometimes  the  latter  gains  the  upper 
hand. 

The  sum  total  of  the  corresponding  points  in  the  binocular  field 
of  vision  producing  a  single  impression,  forms  the  so-called  horopter.^ 
It  differs  with  every  new  position  of  the  eyes  and  may  be  a 
straight  or  a  curved  line,  a  plane  or  a  curved  surface. 

Visual  Judgments. — It  has  been  pointed  out  repeatedly  that  our 
visual  impressions  in  consciousness  are  the  result  of  experience.  Like 
other  sense-organs,  our  eyes  are  the  mere  recipients  of  stimuli  which 
are  moulded  into  concepts  within  the  cortical  realm  of  vision  and  these 
concepts  are  acquired  gradually  by  constant  repetition.  To  begin 
with,  the  infant  receives  these  stimuli  without  being  able  to  interpret 
them,  because  its  association  areas  are  as  yet  incompletely  developed. 
In  the  course  of  a  few  months,  however,  it  begins  to  form  simple  con- 
cepts. It  follows  the  course  of  a  moving  light  with  its  eyes  and  also 
responds  in  other  ways  to  stimuli  of  this  kind.  A  few  months  later 
it  has  learned  to  associate  objects  in  space  in  their  proper  relations, 
irrespective  of  the  fact  that  the  images  upon  the  rods  and  cones  are 
inverted. 

The  adult  being,  therefore,  is  guided  by  the  associations  thus  grad- 
ually acquired  and  does  not  concern  himself  with  the  manner  in  which 
the  images  are  formed  in  the  sense-organ,  i.e.,  the  fact  that  the  objects 
in  space  are  presented  to  him  inverted  he  has  overcome  by  experience 
and  proper  psychic  interpretation.  The  visual  concepts  thus  formed 
are  gradually  brought  into  relation  with  concepts  of  a  different  nature, 
so  that,  for  example,  the  visual  concept  of  a  certain  object  is 
subsequently  correlated  with  its  taste  and  odor  or  with  the  sound 
which  it  may  produce.  A  similar  expansion  of  our  concepts  enables 
us  to  form  judgments  not  only  regarding  the  general  outline  of  objects 
but  also  regarding  their  depth  or  solidity.  Although  the  most  perfect 
results  are  obtained  by  binocular  vision,  one  eye  is  quite  sufficient  to 
obtain  correct  relationships  in  space,  and  to  rate  objects  in  accordance 
with  their  height,  breadth  and  depth.  Obviously,  the  judgment  of 
the  size  of  an  object  is  chiefly  dependent  upon  the  size  of  its  imag3 
upon  the  retina  and  hence,  upon  the  angles  which  its  luminous  rays 
form  with  the  visual  angles  of  the  eyes.  This  requires  accommodation 
by  the  ciliary  mechanism  as  well  as  variations  in  the  position  of  the 
visual  axes  of  the  eyes.  Since  an  object  at  a  distance  of  5  m.  emits 
a  large  number  of  parallel  rays,  practically  no  accommodation  is 
required.  Beyond  this  point,  we  must  rely  chiefly  upon  the  visual 
angle,  while  within  this  distance,  this  factor  is  augmented  by  the  degree 
of  contraction  of  the  ciUary  muscle  as  well  as  by  that  of  the  orbital 
muscles  used  in  converging  the  visual  axes.  Lastly,  our  associations 
are  based   upon   certain  outside  factors,   for  example,  the  character 

^  Johannes    Miiller,    Beitr.    zur  vergl.    Physiol,    der   Sinnesorgane,    1826. 


BINOCULAR  VISION  875 

of  the  air.  Inasmuch  as  the  latter  is  not  entirely  transparent,  distant 
objects  cannot  be  seen  so  clearly  as  near  objects.  In  many  cases, 
this  obscuration  of  the  luminous  rays  of  an  object  frequently  prompts 
us  to  form  an  erroneous  judgment.  Thus,  an  object  dimmed  by  a 
mist  "looms  large,"  because  we  associate  indistinct  vision  with 
distance  and  hence,  the  sudden  relatively  large  visual  image  produced 
by  this  near  object,  leads  us  to  overestimate  its  actual  size. 
Concurrently,   the   size   of   an   object  seen  in  a  clear  atmosphere,  is 


L  R 

Fig.  473. — Right-  and  Left-eyed  Images  of  Truncated  P-j-ramid.  Mat  be  Com- 
bined TO  PRODtcE  Solid  Image  by  Relaxing  the  Accommodation — that  is,  Gazing  to 
A  Distance  Through  the  Book. 

generally     under-valued    for    the    reason    that    distinct    vision    is 
associated  with  near  objects. 

The  judgments  regarding  the  depth  or  solidity  of  objects  are  formed 
in  a  similar  way,  i.e.,  they  are  based  upon  several  factors,  namely: 

(a)  The  difference,  in  the  images  formed  in  the  two  eyes.  Since  the  eyes  are 
separated  from  one  another  by  a  certain  distance,  the  right  eye  sees  more  of  its 
right  side  and  the  left  eye,  more  of  its  left  side.     This  difference  in  the  projection 


Fig.  474. — Stereoscopic  Picture  of  an  Octahedral  Crystal.  May  be  Combined 
Stekeoscopically  by  Relaxing  the  Accommodation  by  the  Method  of  Heteronymous 
Diplopia.     Hold  the  Object  at  a  Distance  of  a  Foot  or  More  and  Gaze  Beyond. 


leads  to  a  corresponding  difference  in  the  associations.  It  becomes  more  pro- 
nounced, the  nearer  the  object. 

(6)  Mathematical  perspective.  Objects  appear  in  relief  and  we  have  learned 
to  interpret  perspective  correctly. 

(c)  Lights  and  shadows  aid  our  judgment  according  to  their  distribution 
through  the  visual  field. 

\d)  The  muscle-sense  plays  a  part  in  accommodation  as  well  as  in  the  con- 
vergence of  the  visual  axes. 

(e)  Condition  of  the  atmosphere.  More  distant  objects  are  not  so  clear  as 
near  objects. 


876 


THE    SENSE    OF    SIGHT 


The  stereoscope. — The  purpose  of  this  instrument  is  to  fuse  non- 
corresponding  images  so  that  they  may  give  rise  to  a  single  visual  con- 
cept possessing  solidity.  Wheatstone^  accomplished  this  end  by 
means  of  mirrors  placed  at  certain  angles  to  one  another,  and  Brewster^ 
by  means  of  two  prisms.  It  has  been  stated  above  that  the  images 
of  a  solid  object  in  binocular  vision,  are  somewhat  different  in  the 
two  eyes,  but  since  they  are  formed  upon  corresponding  points  of  the 
retinae,  they  produce  a  perfectly  harmonious  relief. 

The  stereoscope  serves  to  give  solidity  to  pictures  of  objects  which 
would  otherwise  present  only  two  dimensions,  namely  those  of  height 

and  breadth.  This  fusion  of  two  pic- 
tures is  effected  by  permitting  each  eye 
to  regard  its  own  field  through  a  curved 
prism  composed  of  two  half  lenses  with 
convex  surfaces,  the  inner  margins  of 
which  are  directed  inward.  A  vertical 
screen  is  adjusted  between  the  two 
lenses  in  such  a  way  that  the  sight  of 
the  left  eye  is  entirely  cut  off  from  that 
of  the  right  eye  (Fig.  475).  While  the 
prisms  themselves  tend  to  magnify  the 
pictures,  stereoscopic  views  are  usually 
taken  with  the  help  of  two  lenses  which 
are  separated  by  a  distance  somewhat 
greater  than  the  interocular.  Conse- 
quently, the  solidity  is  in  reality  some- 
what exaggerated.  It  has  been  pointed 
out  above  that  two  identical  pictures 
cannot  give  a  sensation  of  relief,  be- 
cause only  the  psychic  comparison  of 


aj 

Fig.  475. — Diagram  to  Illus- 
trate THE  Principle  of  the  Brew- 
ster Stereoscope. 

P  and  P' ,  the  prisms,  a,  b,  and 
a,  /3,  the  left-  and  right-eyed  pictures, 
respectively,  h,  (3,  being  a  point  in  the 
foreground    and  a,  a,   a  point  in  the 

background.  The  eyes  are  converged  two  slightly  dissimilar  images  can  lead 

and  focused  separately  for  each  point    ^^   ^  perception    of    SoHdity.       In    Other 
as  in  viewing  naturally   an  object  oi  i  i  i    i 

three  dimensions.    (Landois.)  words,  we  have  learned  by  experience 

that  only  those  objects  can  give  rise  to 
this  impression  which  possess  solidity.  Upon  this  basis  rests  the 
psychic  interpretation  of  stereoscopic  pictures. 

Optical  Illusions. — It  appears,  therefore,  that  seeing  is  essentially 
a  process  of  reasoning  in  accordance  with  past  experience.  This 
point  is  clearly  proved  by  the  visual  sensations  of  blind  persons  whose 
sight  has  been  restored  in  later  years  by  the  sudden  relief  of  the  condi- 
tion causing  the  blindness.  Although  these  persons  have  gradually 
formed  an  idea  regarding  the  shape  and  size  of  objects  by 
means  of  the  muscle-sense,  they  are  then  quite  unable  to  tell 
"which  is  which,"  and  several  days  of  repeated  comparison  are  required 

1  Phil,  transactions,  1838. 

^  Edinbourgh  Phil.  Transactions,  1843;  also:  Rollnaan,  Poggend.  Annalen, 
1853. 


BINOCULAR   VISION 


877 


before  they  are  able  to  correlate  their  visual  concepts  with  those  pre- 
viously established  with  the  help  of  the  muscle-sense.  Thus,  one  person 
could  not  tell  which  was  the  dog  and  which  the  cat,  concepts  formed 
sol(>Iy  by  the  muscle-sense,  until  he  had  again  felt  of  the  cat's  tail  and 
general  contours  of  its  body.     In  all  these  cases,  the  persons  made 


C 


D  B 

Fig.  476. — To  Illustrate  the  Illl'sion  of  Subdivided  Space. 

protective  movements,  because  they  felt  as  if  the  objects  were  actually 
touching  their  eyes. 

While  our  visual  judgment  is  something  quite  definite,  we  are  very 
prone  to  form  wrong  concepts  whenever  we  are  subjected  to  unusual 


Fig.  477. — To  Illustrate  the  Over-estimation  of  Vertical  Lines. 


conditions,  such  as  may  be  established  by  changing  the  position  of  our 
body  as  a  whole  or  by  altering  the  configuration  of  the  object.  Thus, 
a  space  subdivided  by  intermediate  lines  seems  larger  than  one  not  so 
interrupted.     Evidently,   it   requires   a  somewhat  greater   muscular 


878 


THE    SENSE    OF    SIGHT 


effort  to  focalize  these  lines  in  succession  than  if  the  eyes  can  sweep 
straight  across  the  open  field.  Quite  similarly,  if  two  equally  large 
squares  are  subdivided  by  an  equal  number  of  horizontal  or  vertical 
lines,  the  one  subdivided  horizontally  will  appear  to  be  larger  from 
below  upward  and  the  other  from  side  to  side  (Fig.  476).  If  we  adjust 
two  lines  of  equal  length  at  right  angles  to  one  another,  the  vertical 


Fig.  478. — Zollner's  Lines. 

one  will  seem  to  be  the  longer  of  the  two  (Fig.  477).  This  deception 
has  been  explained  by  assuming  that  the  contraction  of  the  internal 
or  external  oblique  muscle,  required  to  visualize  the  horizontal  line, 
is  effected  with  a  slighter  expenditure  of  energy  than  that  of  the 
oblique  muscles,  required  to  trace  the  vertical  line.  In  the  latter  case, 
the  tendency  of  the  superior  rectus  to  divert  the  eye  inward,  must  be 


J^ 


B 


Fig.  479. — Muller-Lyer  Figures  to  Show  Illusion  in  Space  Perception. 
A  AND  B  aee  of  the  Same  Length. 


The  Lines 


counteracted  by  the  contraction  of  the  inferior  oblique  which  turns 
the  eye  outward. 

A  very  striking  illusion  may  also  be  produced  by  placing  convergent 
and  divergent  oblique  lines  upon  two  parallel  lines  of  the  same  length. 
In  the  first  case,  the  latter  will  appear  to  come  together,  and  in  the 
second  case,  to  separate  more  widely.     A  similar  effect  may  be  ob- 


COLOR  VISION  879 

tained  with  the  aid  of  tlie  so-called  Zollner's  lines,  represented  in 
Figure  478.  This  illusion  may  be  explained  uiM)n  the  basis  that  we 
tend  to  overvalue  the  size  of  acute  anjjjles.  Fifi;ur(^  479  shows  two 
horizontal  linos  of  the  sanu>  l(Mi<j;t h  which,  however,  ;ue  made  to  appear 
distinctly-  unequal  by  oblique  lines  affixed  to  their  end-points.  Illu- 
sions of  movement  are  now  extensively  employed  in  cinematographic 
pictures.  A  series  of  instantaneous  photographs  having  been  taken 
of  a  moving  object  while  assuming  its  successive  positions,  these  pic- 
tures may  in  turn  be  thrown  upon  the  retipa  in  rapid  sucession  repro- 
ducing the  original  movement. 


CHAPTER  LXXV 
COLOR  VISION 


Qualities  of  Light. — The  ethereal  vibrations  which  are  capable 
of  affecting  our  retinae,  have  different  vibratory  qualities.  White  light, 
such  as  is  emitted  by  the  sun,  is  made  up  of  rays  of  different  wave 
lengths  or  rapidity  of  vibration.  Consequently,  if  a  beam  of  this  light 
is  made  to  impinge  upon  a  plane  medium  of  greater  density,  it  is  split 
into  its  component  rays.  Those  possessing  the  more  rapid  vibratory 
rate,  are  retarded  or  refracted  more  sharply  than  those  characterized 
by  a  slow  vibration.  If  the  aforesaid  medium  is  arranged  in  the  form 
of  a  prism,  this  "dispersion"  or  spreading  of  the  different  rays  will 
be  even  more  apparent.  We  then  obtain  the  so-called  pi-ismatic  or 
solar  spectrum  (Newton  1657),  consisting  of  seven  primary  colors, 
namely  red,  orange,  yellow,  green,  blue,  indigo  and  violet.  These 
colors,  however,  form  a  continuous  series  and  gradually  shade  into 
one  another.  Those  which  stimulate  our  retinae  vary  in  their  vibra- 
tory rate  between  392,000,000,000,000  and  757,000,000,000,000  in  a 
second.  In  round  numbers,  therefore,  it  may  be  said  that  we  are 
subject  to  rays,  the  wave  lengths  of  which  vary  between  400/x)u  to 
800/i/x.^  Under  ordinary  conditions,  however,  we  do  not  recognize 
the  existence  of  these  rays,  because  our  eyes  do  not  possess  the  means 
of  resolving  white  light  into  its  constituents.  Consequently,  this 
analysis  can  only  be  made  outside  of  this  receptor,  and  only  when  the 
retina  is  subjected  to  these  rays  separately,  are  we  in  a  position  to 
recognize  colors.  In  this  regard,  our  eyes  differ  very  materially  from 
the  ear,  because  the  latter  is  equipped  with  a  mechanism  for  analyzing 
sound,  i.  e.,  for  resolving  the  compound  waves  into  their  simple  com- 
ponents. It  should  also  be  remembered  that  the  spectrum  contains 
other  rays  beyond  its  red  and  violet  ends,  and  while  the  latter  do  not 
activate  the  retinae,  they  may  be  made  to  do  so  by  accessory  means. 

'  1  MM  equals  J^Q^Q  ^^- 


880  THE    SENSE    OF    SIGHT 

Beyond  the  red  we  have  rays  of  greater  wave  length,  the  so-called  heat- 
raj'S,  and  bej^ond  the  violet,  raj-s  of  smaller  wave-length,  the  so-called 
chemical  rays.  The  ultra-violet  variety,  however,  maj'  be  raised  above 
the  threshold  of  stimulation  by  rendering  them  fluorescent.  This  is 
true  of  the  Becquerel  (radium)  and  Rontgen  rays,  the  latter  causing 
a  fluorescence  of  the  retina.-^ 

It  will  be  seen,  therefore,  that  the  sensations  of  color  are  due  to 
impacts  upon  the  retina  of  ether  waves  of  definite  length,  whether  they 
be  derived  from  a  homogeneous  beam  or  from  a  mixture  of  simple  lights. 
Besides  the  mere  color  which  is  dependent  upon  the  rate  of  vibration, 
these  sensations  are  also  modified  by  the  intensit}'  or  energy  of  the 
vibrations  as  well  as  by  the  saturation  of  the  primarj^  color.  The 
intensity  of  the  stimulation  gives  rise  to  luminosity  or  hri-ghtness. 
Thus,  it  will  be  found  that  the  extreme  red  and  violet  ends  of  the  spec- 
trum are  less  luminous  than  the  yellow.  Furthermore,  while  we  are 
able  to  tell  which  of  two  red  or  green  colors  is  the  brighter  and  are  even 
able  to  match  them  by  increasing  the  intensity  of  the  beam  of  light, 
we  fail  absolutely  when  attempting  to  arrange  different  colors  in  strict 
accordance  with  their  brightness.  These  tests,  however,  may  be 
greatly  varied  bj'  changing  the  illumination.  This  is  shown  by  the 
fact  that  a  colored  object  appears  colorless  in  low  intensities  of  light, 
and  that  the  brightness  of  the  spectrum  is  then  shifted  from  the  j-ellow 
to  the  green  (Purkinje's  phenomenon).  The  saturation  of  a  color  is 
dependent  upon  its  admixture  with  white  light.  Thus,  a  perfectly 
saturated  color  is  one  entirelj-  free  from  ordinary  white  light,  and  a 
thoroughly  colored  object,  one  which  reflects  specific  color  raj's  and  no 
white  rays.  Physically,  it  is  not  difficult  to  estabUsh  this  condition, 
because  all  we  need  to  do  is  to  restrict  the  beam  of  light  to  specific 
spectral  raj'S.  Physiologically,  on  the  other  hand,  color  sensations 
are  general^  not  pure,  because  even  monochromatic  light  appears  to 
give  rise  to  sensations  of  white  which  are  thus  made  to  intermingle 
with  the  particular  color  sensation.  In  other  words,  while  the  physical 
saturation  of  a  color  may  be  complete,  the  phj-siological  saturation  is 
generally  incomplete. 

Color  Fusion. — In  the  same  wa}-  as  white  Hght  maj'  be  divided  into 
its  components,  so  may  the  different  spectral  colors  be  reunited  into 
white  hght.  This  can  be  done  verj'  easily  by  placing  suitable  lenses 
in  the  path  of  the  colored  raj's  emerging  from  a  prism.  It  should 
also  be  noted  that  white  hght  may  be  produced  bj'  combining  only 
two,  three,  four,  five,  or  six  of  the  original  seven  spectral  colors.  Any 
two  colors  which  give  rise  to  a  sensation  of  white  are  known  as  "com- 
plementary colors." 

A  de\ace  most  commonl}'  employed  to  stimulate  the  retina  simul- 
taneously with  two  or  more  colors  is  the  color-wheel  of  Maxwell.  It 
consists  of  a  rotating  axis  to  which  may  be  attached  discs  of  colored 

1  Birch-Hirschfeld,  Archiv  fur  Ophthalm.,  Iviii,  1904,  469. 


COLOR   VISION 


881 


pasteboard.  The  latter  are  slit  radially  from  periphery  to  center  so 
that  they  may  be  lapped  over  v.iich  other  to  expose  a  larger  or  smaller 
segment  of  each.  Another  method  is  to  superimpose  different  sections 
of  the  spectrum  upon  a  screen  by  means  of  a  system  of  lenses  or  mir- 
rors. In  either  case,  this  physiological  mixing  of  colors  cannot  be  com- 
pared with  that  employed  by  the  painter.  Thus,  a  blue  and  yellow 
pigment  when  mixed,  give  rise  to  the  sensation  of  green  and  not  of 
white,  because  these  two  colors  combined  absorb  all  the  rays  excepting 
the  green,  the  latter  only  being  reflected  into  the  eye.  When  used 
alone,  the  former  appears  blue,  because  it  allows  only  the  blue  and 
some  of  the  green  rays  to  be  reflected,  while  the  latter  appears  yellow 
because  it  absorbs  all  the  rays  excepting  the  yellow.  Consequently, 
when  we  mix  these  colors  we  obtain  a  subtraction,  the  blue  pigment 


<  2  S 

Fig.  480. — Rothe's  Rotatory  Apparatus  for  Color  Discs.     It  is  so  Arranged  as  to 
Grv'E  Various  Rates  of  Rotation  by  Combining  the  Motions  of  1,  2,  and  3. 

absorbing  the  red  rays  which  the  yellow  pigment  lets  pass,  while  the 
yellow  pigment  absorbs  the  blue  rays  which  the  blue  allows  to  pass. 
Thus,  only  the  green  rays  are  left  over. 

The  colors  which  may  be  arranged  in  a  series  of  pairs  to  give  white 
are  the  following: 

Wave-lengths. 

Red  and  greenish  blue 656-492 

Orange  and  blue 608-490 

Bright  yellow  and  blue 574-482 

Yellow  and  indigo 567-465 

Greenish  yellow  and  violet 564-433 

The  fusion  of  a  pair  of  colors  lying  closer  together  than  their  com- 
plementary colors,  yields  an  intermediate  color  which  becomes  more 
completely  satui'ated  or  free  from  white,  the  nearer  they  are  to  one 
another.  Thus,  the  union  of  red  and  yellow  gives  rise  to  orange, 
but  the  latter  is  less  saturated  than  the  corresponding  spectral  color. 
In  the  former  instances,  for  example,  rays  of  656  mm  and  564  /xju  are 

56 


882  THE    SENSE    OF    SIGHT 

mixed,  while  the  spectral  orange  possesses  a  wave  length  of  608  ix/jl. 
Colors  which  are  more  widely  separated  than  the  complementary  colors, 
produce  a  sensation  of  purple  which  is  not  a  spectral  color  at  all  but 
may  be  obtained  by  combining  red  with  violet,  the  two  spectral  ex- 
tremes. If  one  or  the  other  of  a  pair  of  complementary  colors  is  added 
in  excess,  the  resultant  sensation  is  a  color  similar  to  the  one  present 
in  excess  with  more  white  mixed  in  with  it.  Supposing  that  we  em- 
ploy orange  and  blue,  with  the  blue  present  in  greater  amount  than  is 
necessary  to  produce  white,  the  result  is  an  unsaturated  blue,  i.e., 
pale  blue. 

Visual  After-effects. — The  fusion  of  the  colors  described  in  the 
preceding  paragraphs,  depends  upon  the  persistance  of  the  individual 
stimulations,  a  second  color  being  thrown  upon  the  retina  before  the 
first  sensation  has  had  sufficient  time  to  disappear.  This  is  really  true 
of  all  visual  impressions,  because  they  invariably  last  longer  than  the 
stimulus.  Everything  else  remaining  equal,  these  after-images  depend 
in  a  large  measure  upon  the  intensity  of  the  primary  stimulus,  i.e., 
upon  its  strength  and  duration.  Thus,  an  electric  spark  generally 
leaves  a  very  decided  impression  in  consciousness,  because  it  is  intense 
although  of  very  brief  duration.  Quite  similarly,  if  one  looks  at  the 
light  of  a  candle,  and  then  closes  his  eyes,  this  image  persists  for  some 
time  thereafter  in  its  natural  colors.  It  then  fades  away,  meanwhile 
undergoing  certain  changes  from  greenish  blue  to  indigo,  violet,  rose 
and  pale  orange.  But  this  phenomenon  is  not  restricted  to  mere 
white-black  impressions,  but  also  to  specific  colors.  In  any  case,  we 
designate  them  as  positive  after-images,  because  they  do  not  change 
their  original  character.  Negative  after-images,  on  the  other  hand,  do 
not  retain  their  character,  but  assume  colors  complementary  to  those 
of  the  object  producing  them.  White  becomes  black,  red  a  bluish 
green,  yellow  an  indigo  blue,  and  so  on.  These  images  are  obtained 
more  frequently  than  those  of  the  positive  kind  and  may  be  produced 
in  the  following  way.  If  we  gaze  intently  for  a  few  moments  at  a  red 
disc  upon  a  white  surface  and  then  at  a  uniform  white  background, 
an  after-image  of  this  disc  is  obtained  which,  however,  appears  green, 
while  the  background  assumes  a  reddish  shade.  This  phenomenon  is 
usually  explained  upon  the  basis  of  fatigue  of  the  retina  toward  this 
particular  color,  although  it  is  difficult  to  reconcile  this  hypothesis 
with  all  the  facts.  Nevertheless,  it  is  easy  to  understand  that  the 
after-image  must  appear  in  the  complementary  color,  because  the  reti- 
nal component  producing  the  sensation,  say  of  red,  has  been  considerably 
reduced  by  the  exposure,  while  its  greenish-blue  element  is  still  present 
in  normal  amounts  and  is,  therefore,  still  able  to  produce  its  character- 
istic effect. 

Contrast. — If  we  place  a  small  white  disc  upon  a  larger  black  field, 
the  former  appears  whiter  than  it  would  if  not  contrasted  in  this  way. 
Quite  similarly,  a  small  black  dot  adjusted  upon  a  white  general  field 
appears  much  darker  in  color  than  one  resting  upon  a  background  of 


COLOR  VISION 


883 


another  quality,  and  a  pioco  of  red  paper  Iield  apainst  a  red  background, 
does  not  appear  nearly  so  saturated  as  one  contrasted,  say,  against 
white.  A  similar  contrast  may  be  obtained  by  rotating  a  white  disc 
containing  a  certain  amount  of  black,  as  illustrated  in  Fig.  481.  On 
rotation  this  disc  ought  to  yield  uniform  circles  of  gray,  their  bright- 
ness being  least  in  the  center.  Instead,  each  circles  presents  a  darker 
outer  and  lighter  inner  margin,  because  the  former  borders  on  a  zone 
darker  than  itself,  while  the  latter  borders  upon  a  zone  lighter  than 
itself. 

These  phenomena  of  contrast  may  also  be  extended  to  colors. 
Thus,  if  a  piece  of  gray  paper  is  placed  upon  a  larger  green  sheet,  the 
former  appears  pink  or  rose-red.  TJie  intensity  of  the  latter  color  may 
be  increased  by  covering  the  whole  with  a  sheet  of  tissue-paper.  It 
may  also  be  illustrated  by  the  approximation  of  colored  shadows. 


A  B 

Fig.  481. — A,  Black  and  White  Disc  for  Experiment  on  Contrast;  B,  Showing  the 

Result  When  the  Disc  A  is  Set  into  Rapid  Rotation.     (Rood.) 


This  can  be  done  by  placing  an  object  of  suitable  size  and  shape  upon 
a  white  background  and  illuminating  it  from  one  side  with  day-light 
and  from  the  other  with  gas-light.  Two  shadows  result  which  are 
sharply  contrasted  against  one  another.  The  one  thrown  by  the  gas- 
light appears  yellow,  while  the  one  produced  by  the  day-light  exhibits 
a  bluish  tint,  for  the  reason  that  it  is  contrasted  against  the  general 
yellowish  illumination. 

The  hypothesis  of  Helmholtz  which  refers  contrast  to  an  erroneous 
judgment,  has  been  severely  criticized  by  Hering  who  holds  that  this 
phenomenon  is  due  to  the  opposing  influences  of  two  different  regions 
of  the  retina  and  the  visual  association  areas  corresponding  to  them. 
Hering,  therefore,  ascribes  them  to  the  peripheral  part  of  the  visual 
mechanism  and  removes  from  them  any  purely  psychic  character. 
Evidently,  he  imagines  them  to  be  opposing  processes  of  assimilation 
and  dissimilation,  similar  to  those  occurring  during  color  vision.  This 
implies  that  while. a  dissimilation  of  a  particular  substance  may  be 
going  on  in  one  part  of  the  retina,  a  neighboring  area  may  show  assim- 
ilation.    McDougall  compares  these  phenomena  of  contrast  to  the 


884 


THE    SENSE    OF    SIGHT 


inhibitor  processes  going  on  in  the  spinal  cord  during  reciprocal  inner- 
vation. It  has  been  pointed  out  by  Sherrington  that  the  extensor  or 
stepping  reflex  may  be  inhibited  by  evoking  the  flexor  reflex.  In  an 
analogous  manner  it  is  supposed  here  that  the  excitation  of  one  part 
of  the  retina  prevents  similar  processes  from  developing  in  neighboring 
regions  or  in  the  neurons  innervating  them. 

The  Sensibility  of  the  Retina  to  Colors. — It  will  be  remembered 
that  the  perhneter  is  used  to  map  out  the  visual  field  for  ordinary 
objects.  It  may  also  be  employed  for  studying  the  distribution  of  the 
color  sense  by  simply  replacing  the  small  white  disc  by  discs  of 
different  colored  paper.  By  bringing  the  latter  into  the  line  of 
vision  along  the  different  meridians  of  the  eye,  it  will  be  found  that 
the  extreme  outer  zone  of  the  retina  is  color  blind  and  perceives  only 


Fig.  482. — Perimeter  Chart  Indicating  the  Average  Fields  of  Vision  for  Blue,  Red, 
AND  Green  Compared  with  White  (Gray).     {Howell.) 

objects  as  such.  Somewhat  nearer  the  center  of  the  visual  field,  we 
perceive  first  blue,  then  red,  and  lastly,  green.  Consequently,  the 
retina  may  be  divided  into  three  concentric  color  zones,  namely,  a 
peripheral  one  for  black  and  white,  an  intermediate  one  for  yellow  and 
blue,  and  a  central  one  for  red  and  green.  It  is  to  be  noted,  however, 
that  these  zones  are  rarely  identical  in  the  retinae  of  different  individu- 
als and  may  even  present  marked  irregularities  in  one  and  the  same 
person.  But,  many  of.  these  variations  are  referable  to  differences  in 
the  relative  saturation  of  the  colors  employed  for  this  test.^     Most 

^  Baird,   The  color  sensibility  of  the  peripheral  retina,  Publ.  Carnegie  Insti- 
tution, No.  29,  1905. 


COLOR   VISION 


885 


peculiar  abridgments  of  the  color  field  result  in  consequence  of  diseases 
of  the  retina,  and  optic  nerve  or  of  lesions  of  the  visual  association  area. 


06t      081      OLl 


Fig.  483. — Periaieteb  Chart  Showing  the  Highly  Restricted  Color  Fields  es"  the 
Left  Eye  of  a  Ty^pical  C.^e  of  So-called  Red-greex  Color  Blindness.      (Howell.) 

Theories  of  Color  Vision. — It  has  been  pointed  out  above  that  the 
rods  and  cones  are  somewhat  different  in  their  function.  From  the 
standpoint  of  color  vision  it  is  now  commonly  believed  that  the  former 


Fig.  484. — Diagr.a:«  to  Illustrate  the  Youxg-Helmholtz  Theory  of  Color 
Vision.  Verticai^  Drawn  at  ant  Point  of  the  Spectrum  In'dicate  the  Relative 
Amount  of  Stimulation  of  the  Three  Substances  for  that  Wave  Length  of  the 
Spectrum.     (Helmholtz.) 

which  alone  are  present  in  the  zone  adjacent  to  the  ora  serrata,  are 
concerned  with  achromatic  vision  in  low  intensities  of  light,  while  the 
latter  are  employed  for  color  vision  as  well  as  for  achromatic  vision 
in  ordinary  intensities  of  light.     This  conclusion,  however,  does  not 


886 


THE    SENSE    OF   SIGHT 


furnish  an  adequate  explanation  for  this  function,  but  simply  leads  to 
certain  assumptions  which  have  been  embodied  in  the  theories  now 
to  be  discussed.^  It  must  be  emphasized,  however,  that  the  latter  are 
really  mere  hypotheses  lacking  a  sound  experimental  basis.  All  of 
them  assume  the  existence  in  the  retina  of  certain  fundamental  sub- 
stances which  are  instrumental  in  effecting  the  primary  sensations  of 
color,  and  the  only  difference  between  them  really  lies  in  the  manner 
in  which  these  pigments  are  distributed. 

The  Young-HelmhoHz  theory  which  was  first  advocated  by  Young  but  has  later 
on  been  greatly  elaborated  by  Helmholtz,^  assumes  the  presence  of  three  primary 
color  sensations,  designated  as  red,  green  and  violet  (Fig.  484,  1,  2  and  3).  These 
sensations  arise  in  consequence  of  the  activation  of  three  separate  photo-chemical 


Fig.  485. — Diagram  to  iLLrsTRATE  the  Hering  Theory  of  Color  Vision. 
The  curves  indicate  the  relative  intensities  of  stimulation  of  the  three  color  substances 
by  different  parts  of  the  spectrum.  Ordinates  above  the  axis,  A^-A',  indicate  catabolic 
changes  (dissimilation),  those  below  anabolic  changes  (assimilation).  Curve  a 
represents  the  conditions  for  the  black-white  substance.  It  is  stimulated  by  all  the 
rays  of  the  visible  spectrum  with  maximum  intensity  in  the  yellow.  Curve  c  represents 
the  red-green  substance,  the  longer  wave  lengths  causing  dissimilation  (red),  the 
shorter  ones  assimilation  (green).  Curve  b  gives  the  conditions  for  the  yellow-blue 
substance.      (Foster.) 


substances  which,  on  being  struck  by  the  rays  of  light,  undergo  a  decomposition 
and  generate  nerve  impulses  peculiar  to  each  of  them.  The  red  substance  is 
reduced  by  the  rays  of  long  wave-length,  the  green  substance  by  rays  of  medium 
wave-length,  and  the  violet  substance  by  rays  of  short  wave-length.  When  these 
chemical  elements  are  excited  in  an  equal  measure,  the  result  is  the  sensation  of 
white  or  gray,  while  no  stimulation  at  all  yields  black.  The  other  sensations  of 
color  are  compound  in  their  nature,  i.e.,  they  are  dependent  upon  the  joint  stimu- 
lation of  all  three  substances  in  diflPerent  proportions.  Thus,  yellow  is  the  re-sult 
of  an  excitation  of  the  red  and  green  elements  and  blue,  the  result  of  an  activation 
of  the  green  and  violet  substances. 

The  Hering  theory  of  color  vision  assumes  the  presence  of  four  primary  sensa- 
tions of  color,  namely,  red,  yellow,  green  and  blue.  These  sensations,  however,  are 
supposed  to  be  produced  by  two  groups  of  photo-chemical  substances,  namelj^,  red- 

1  Calkins,  Archiv  fiir  Physiol.,  1902,  244. 

2  Handb.  der  physiol.  Optik,  Berlin,  1896. 


COLOR   VISION  887 

greon  and  y('llo\v-l)liie.  To  these  is  then  added  a  wliito-hlack  substance,  so  that 
we  have  in  reality  three  pairs  of  recipient  elements.  Actual  sensations  of  color  are 
derived  from  these  groups  of  substances  by  processes  of  assimilation  and  dis- 
similation, as  follows: 

Dissimilation  Assimilation 

Red-green red green 

Yellow-blue yellow blue 

Whit('-i)lack white black 

Like  all  other  constituents  of  our  body,  these  substances  are  first  broken  down  and 
then  again  reformed.  They  undergo  catabolism  and  anabolism.  Thus,  if  white 
light  falls  upon  the  retina,  the  white-black  pigment  is  reduced,  this  process 
giving  n.se  in  consciousness  to  the  sensation  of  white.  As  soon  as  this  stimulation 
ceases,  the  white-black  substance  is  reformed,  setting  up  in  consciousness  the  sen- 
sation of  black.  But,  this  recipient  is  also  aflfected  by  rays  of  different  wave-lengths 
so  that  the  sensations  of  white  and  black  frequently  occur  together  with  those  of 
the  other  colors.  The  yellow-blue  and  red-green  recipient  elements,  however,  are 
affected  exclusively  by  rays  of  their  specific  wave-lengths. 

The  Lndd-Franklin  theory  of  color  vision^  assumes  that  the  colorless  sensations 
of  white,  gray  and  black  are  produced  bj'  the  excitation  of  a  photo-chemical 
substance,  designated  as  gray.  While  this  recipient  element  is  present  in  the  rods 
as  well  as  in  the  cones,  only  the  latter  contain  it  in  a  form  to  give  rise  to  sensations 
of  different  colors.  On  exposure  to  light  this  substance  is  dissociated,  the  result 
being  difTerent  shades  of  gray.  This  is  the  onh^  reaction  possible  in  the  rods,  and 
hence,  these  elements  give  rise  exclu-sivel}'  to  this  particular  sensation.  In  the 
coneS:  on  the  other  hand,  this  substance  is  present  in  a  differentiated  form,  allow- 
ing the  development  of  more  complex  reactions.  The  molecules  of  gray  substance 
here  assume  a  multiple  form  so  that  only  certain  portions  of  them  are  dissociated 
by  the  light.  The  molecular  substance  is  divided  into  two  parts,  one  of  which  is 
sensitive  to  the  rays  of  slow  vibration,  and  the  other  to  those  of  rapid  vibration. 
The  excitation  of  the  first  yields  yellow  and  that  of  the  second  blue.  The  yellow 
recipient  is  again  divided  into  two  parts,  one  of  which  receives  the  longest  visible 
rays  (red)  and  the  other  the  rays  giving  rise  to  the  spectral  green.  Thus,  the  com- 
plete dissociation  of  the  red,  green  and  blue  recipients  produces  gray,  while  the 
simultaneous  dissociation  of  the  red  and  green  evokes  the  same  sensation  as  the 
dissociation  of  the  entire  yellow  recipient. 

Since  this  theory  necessitates  certain  new  chemical  conceptions  pertaining  to  the 
differentiation  of  the  molecule,  and  its  complete  and  partial  dissociation,  it  cannot 
be  regarded  as  anything  more  than  a  provisional  explanation  until  definite  experi- 
mental proof  has  been  furnished  for  these  contentions.  It  is  true,  however,  that 
it  accounts  for  certain  facts  pertaining  to  color-blindness  in  a  more  accurate  man- 
ner than  the  two  theories  mentioned  previously.  In  addition,  it  furnishes  an 
explanation  for  the  variations  in  the  visual  sensations  mediated  by  the  peripheral 
zone  of  the  retina. 

Color-blindness. — The  terms  of  amblyopia  and  amaurosis  are 
employed  to  indicate  an  obscurity  and  loss  of  sight.  In  this  category 
are  also  placed  certain  congenital  defects  of  the  sense  of  color  which 
are  present  in  about  3  per  cent,  of  the  eyes  examined,  but  are  relatively 
rare  in  woman.  In  most  cases,  both  eyes  are  affected  and  a  hereditary 
tendency  is  unmistakable.  It  also  seems  that  this  disorder  is  more 
common  among  the  poorly  educated  classes.  ^ 

1  Psychological  Review,  1894,  1896  and  1899. 

2  Holmgren,  Color  Blindness  in  its  Relations  to  Accidents  by  Rail  and  Sea, 
Smithsonian  Institution  Reports,  1878. 


THE    SENSE    OF    SIGHT 

Repeated  attempts  have  been  made  to  harmonize  the  facts  of 
color-bhndness  with  the  hypotheses  outhned  in  the  preceding  para- 
graphs. But,  inasmuch  as  this  is  almost  impossible,  it  seems  permis- 
sible to  adopt  a  perfectly  empirical  classification  and  to  state  that 
one  group  of  color-blind  is  characterized  by  an  absence  of  the  power 
to  perceive  colors,  while  the  other  experiences  merely  a  difficulty 
in  distinguishing  colors.  The  first  possess  achromatopsia  and  the 
latter  dyschromatopsia,  but  even  the  former  condition  is  rarely 
complete,  excepting  in  cases  of  definite  pathological  changes  in  the 
optic  nerve.  ^  Consequently,  even  the  achromatopic  person  is 
capable  of  recognizing  one  or  more  fundamental  colors.  Attention, 
however,  should  be  called  to  the  fact  that  the  absence  of  a  particular 
color  from  the  spectrum  does  not  imply  that  perception  of  its  lumi- 
nosity has  been  interfered  with.  A  person  may  well  be  able  to  recognize 
the  spectrum  throughout  its  entire  length  and  yet  be  unable  to  dis- 
tinguish more  than  two  colors,  say,  red  and  violet. 

Upon  the  basis  of  the  Helmholtz  theory,  we  may  divide  color- 
blindness into  blue,  green  and  red-blindness.  The  most  common  of 
these  is  the  red-blindness,  in  which  the  red  end  of  the  spectrum  is  consid- 
erably shortened.  A  person  so  afflicted  confounds  light  red  colors  with 
dark  green  and  cannot  see  a  dark-red  square  upon  a  black  background. 
In  fact,  the  most  typical  cases  show  a  green-blindness  and  are  capable 
of  distinguishing  only  the  yellows  and  blues.  Consequently,  the  red, 
orange  yellow,  and  green  appear  to  them  merely  as  different  shades  of 
yellow,  while  the  green  is  perceived  as  gray  and  the  indigo,  violet,  and 
purple  seem  blue.  A  person  afflicted  with  green-blindness  confounds 
light-green  with  dark  red  and  does  not  recognize  a  dark  green  square 
upon  a  black  background,  but  can  perceive  a  red  square  upon  black. 
In  many  cases,  however,  they  also  show  a  certain  interference  with 
the  red  end  of  the  spectrum  and  hence,  are  really  green-red  blind, 
although  they  differ  from  the  red-green  blind  in  certain  minor  par- 
ticulars. A  person  afflicted  with  blue-blindness,  sees  only  red  and 
green  and  confounds  blue  with  green,  purple  with  red,  orange  with 
yellow,  and  violet  with  yellow-green.  This  condition  indicates  a 
shortening  of  the  violet  end  of  the  spectrum.  Blue-bhndness  of  a 
temporary  kind  may  be  produced  by  the  ingestion  of  santonin. 

Color-vision  is  commonly  tested  by  means  of  a  number  of  skeins 
of  wool,  exhibiting  three  colors,  namely,  a  pale  pure  green,  a  medium 
purple,  and  a  vivid  red  (Holmgren).  The  person  suspected  to  be 
color-bhnd  is  asked  to  match  the  pale  green  skein.  If  red  or  green 
blind,  he  will  recognize  this  skein  as  gray  with  some  admixture  of 
yellow  or  blue  and  will  match  it  not  only  with  the  green  skeins  but 
also  with  those  possessing  a  grayish  yellow  or  blue  color.  If  he  is 
then  asked  to  match  the  medium  purple  skein,  he  will  select  either 

1  Siven  and  Wendt,  Skand.  Archiv  fur  Physiol.,  xiv,  1903,  196,  and  Grunert, 
Archiv  fur  Ophtbalm.,  liii,  1903,  132. 


COLOR   VISION  889 

the  different  purples,  the  blues  and  violets,  or  only  the  greens  and 
grays.  In  the  first  instance,  tliis  would  signify  that  he  is  red-blind, 
and  in  the  second  that  he  is  green-l)lind.  If  the  red-bhnd  is  then  asked 
to  match  the  red  skein,  he  will  pick  out  the  greens,  grays  and  browns, 
possessing  a  luminosity  less  than  that  of  the  test  color,  while  the  green- 
blind  will  select  the  greens,  grays  and  browns  of  greater  luminosity. 


PART  VII 
SECRETION 


SECTION  XXIV 
THE  "EXTERNAL"  SECRETIONS 


CHAPTER  LXXVI 


THE  GROUP  OF  THE  CUTANEOUS  SECRETIONS 

Classification  of  the  Secretions. — A  secretion  is  a  cellular  product 
which  is  of  further  use  to  the  body,  while  an  excretion  is  a  cellular 
product  which  is  of  no  further  use  to  the  body.  Obviously,  this 
definition  must  be  held  within  very  general  limits,  because  not  all 
secretions  and  excretions  are  fluids.  It  will  also  be  remembered  that 
the  secretions  are  formed  by  special  colonies  of  cells  which  oresent 
themselves  as  "external"  and  "in- 
ternal" glands.  The  former  possess 
a  visible  duct  through  which  the 
secretion  escapes,  while  the  latter 
do  not,  and  constitute,  therefore,  the 
group  of  the  so-called  ductless  glands. 
Consequently,  while  the  "external" 
secretions  are  poured  upon  an  open 
surface  of  the  body,  the  internal  se- 
cretions are  discharged  directly  into 

the  blood  or  lymph  stream.      For  this    Fi«-  486.— Diagrammatic   Representa- 
, ,         »  .  ,,  TiON  OF  AN  Acinus. 

reason,   the   former  most   generally     r>  t^    ^   o         .  n     r    i       u 

°  ,  .,       ,  X),  Duct;  <S,  secretory  cells;  L,  lymph 

give  rise  to  local  reactions,  while  the  space;  C,  blood  capillaries. 

latter  are  distributed  throughout  the 

body  and  aid  in  the  promulgation  of  physiological  processes  of  a  more 
general  and  intricate  kind.  This  relatively  sharp  line  of  demarcation 
already  drawn  between  the  "external"  and  "internal"  secretions,  may 
be  elucidated  further  by  briefly  noting  the  histological  character  of 
the  glands  producing  them.  The  external  glands  invariably  exhibit 
a  structure  which  betrays  its  secretory  nature  almost  immediately, 
while  that  of  the  internal  glands  is  generally  obscure  and  cannot 
readily  be  associated  with  secretion. 

A  secreting  mechanism  consists  essentially  of  a  colony  of  cells 
which  are  arranged  around  a  central  cavity  or  tube  for  the  reception 

891 


892  THE    EXTERNAL    SECRETIONS 

of  their  product.  The  material  required  for  the  formation  of  the 
secretion,  is  derived  from  an  intricate  system  of  capillaries  situated 
in  the  immediate  vicinity  of  their  walls.  These  cells  are  arranged  in 
groups  forming  the  so-called  acini.  By  combining  many  of  these  acini 
we  obtain  a  lobule.  Several  lobules  constitute  a  lobe  and  several 
lobes  the  gland  as  a  whole.  In  general,  it  may  be  said  that  glands 
are  either  tubular  or  racemose  in  character  and  may  be  either  simple 
or  compound.  As  an  example  of  a  simple  tubular  gland,  we  might 
mention  the  sweat  glands  of  the  skin  or  the  crypts  of  Lieberkiihn 
of  the  small  intestine;  and  as  an  example  of  a  compound  tubular  gland, 
the  glands  of  the  pyloric  end  of  the  stomach  or  those  of  the  tongue 
or  uterus.  Simple  racemose  or  alveolar  glands  are  those  furnishing 
the  sebaceous  material  for  the  skin,  and  compound  racemose  glands 
those  furnishing  the  saliva.  Some  glands,  such  as  the  pancreas,  are 
of  a  mixed  type,  combining  some  of  the  characteristics  of  the  tubular 
with  those  of  the  racemose  variety.  They  are  called  tubulo-racemose 
glands. 

The  Factors  Concerned  in  the  Formation  of  a  Secretion. — It  was 
formerly  believed  that  secretions  and  excretions  are  the  products  of 
a  process  of  filtration.  It  was  conceived  that  the  different  cells  of  the 
alveoli  form  a  passive  membrane,  through  which  the  blood  plasma 
percolates  from  a  place  of  high  pressure  to  a  place  of  low  pressure.  Ob- 
viously, this  mechanism  may  be  represented  in  a  plastic  manner 
by  adjusting  a  glass  funnel  lined  with  filter  paper  above  a  beaker. 
The  solution  poured  upon  this  paper  takes  the  place  of  the  blood,  because 
some  of  its  constituents  are  forced  by  pressure  through  the  paper  into 
the  receptacle  underneath.  In  accordance  with  the  pure  filtration 
theory,  the  differences  in  the  character  of  secretions  are  the  result  of 
variations  in  the  structure  and  chemical  properties  of  the  dialyzing 
membrane  and  not  of  an  active  metabolism  of  its  cellular  constituents. 
Later  on  this  theory  was  modified  by  the  addition  of  the  factors  of 
osmosis  and  diffusion,  but  even  in  this  case,  the  epithelium  remains 
a  passive  membrane  through  which  these  osmotic  interchanges  between 
the  blood  and  the  secretion  are  effected  in  accordance  with  ordinary 
physical  laws. 

These  factors  which  have  been  combined  by  Ludwig  and  his  pupils, 
into  the  so-called  mechanistic  theory  of  secretion,  were  soon  found  to 
be  inadequate,  because  they  failed  to  explain  many  of  the  phenomena 
connected  with  this  process.  Thus,  it  was  found  that  the  histological 
picture  of  the  resting  gland  is  widely  different  from  that  of  the  active 
gland,  and  that  in  many  cases  the  constituents  of  the  cells  could  be 
traced  directly  into  the  ducts.  This  was  followed  by  the  discovery 
of  distinct  secretory  nerves,  and  lastly,  by  the  observation  that  glandu- 
lar processes  may  also  be  markedly  influenced  by  chemical  means 
and  frequently  furnish  a  product  which  is  not  present  in  the  blood. 
All  these  data  were  eventually  combined  into  the  so-called  chemical  or 
vitalistic  theory  of  secretion,  the  chief  advocate  of  which  was  Heidenhain. 


GROUP  OF  THE  CUTANEOUS  SECRETIONS         893 

It  is  to  be  emphasized,  however,  that  this  chemical  theory  does  not  ex- 
chide  filtration  nor  osmosis  and  diffusion  as  causative  factors,  but 
nnu'ely  states  that  these  processes  are  modified  by  certain  intracellular 
reactions,  the  nature  of  which  is  as  yet  not  fully  understood.  Heidcn- 
hain  included  the  latter  under  the  term  of  vitalism.  It  is  to  be  clearly 
understood,  however,  that  this  term  does  not  refer  to  metaphysical 
phenomena,  but  simply  to  a  still  inex))licable  vital  activity  of  the 
substance  of  the  cells.  This  implies  that  the  latter  do  not  act  merely 
as  passive  filters,  but  influence  the  secretion  by  their  metabolic  changes. 

Since  the  internal  secretory  organs  will  be  more  fully  described  in 
a  subsequent  chapter,  the  present  discussion  may  be  restricted  to  the 
"external"  secretions.  Several  of  these  have  already  been  alluded  to 
in  the  preceding  paragraphs,  for  example,  the  cerebro-spinal  fluid, 
the  intraocular  fluid,  the  tears  and  the  fatty  material  of  the  Meibomian 
follicles  of  the  eyelids.  There  still  remain  to  be  considered  the  sweat, 
the  milk,  the  mucous  secretion  of  the  buccal  and  oral  glands,  as  well  as 
the  lymphatic  secretions  and  the  very  important  group  of  the  digestive 
juices,  formed  by  the  saliva,  gastric  juice,  duodenal  juice,  bile,  pan- 
creatic juice  and  intestinal  juice. 

The  Skin  as  an  Organ  of  F*rotection. — The  skin  consists  of  the  epi- 
dermis or  cuticle  and  dermis  or  cutis  vera.  The  former  appears  as  a 
layer  of  stratified  epithelium  measuring  0.08  to  0.12  mm.  in  thickness. 
Its  deepest  layer  or  rete  Malpighii  is  composed  of  protoplasmic  nucle- 
ated cells,  possessing  a  cylindrical  shape.  The  cells  of  the  surface 
layer,  on  the  other  hand,  are  hard  and  horny,  non-nucleated,  flat- 
tened chips  which  are  constantly  discharged,  their  places  being  taken 
by  new  cells  arising  from  the  rete  Malpighii.  While  being  gradually 
pushed  outward,  the  latter  assume  the  physical  and  chemical  char- 
acteristics of  the  surface  cells  Pigment  cells  are  found  in  the  deeper 
cells  of  the  epidermis  as  well  as  in  those  of  the  corium;  in  the  former, 
however,  the  pigment  is  disseminated  while  in  the  latter,  it  is  restricted 
to  particular  cells.  From  here  this  pigment  is  said  to  migrate  into 
the  more  external  Malpighian  layer,  a  contention  which  fully  explains 
the  fact  that  the  skin  of  a  white  person,  grafted  to  a  negro,  presently 
becomes  thoroughly  pigmented. 

With  the  exception  of  the  palms  of  the  hands,  soles  of  the  feet, 
dorsal  surfaces  of  the  last  phalanges,  glans  penis  and  certain  parts  of 
the  labia,  the  skin  is  beset  with  larger  and  smaller  hairs.  These  ap- 
pendages are  epidermal  growths  contained  in  the  skin  pits  or  hair 
follicles.  The  part  within  the  follicles  is  known  as  the  hair-root. 
Physically  hairs  are  characterized  by  their  marked  elasticity  and  co- 
hesion, which  properties  render  them  capable  of  supporting  a  weight 
of  as  much  as  60  grams.  They  are  very  resistant,  because  composed 
of  a  pigmented,  horny,  fibrous  material;  and  are  strongly  hygroscopic, 
a  propert}^  which  explains  the  painful  sensations  generally  experienced 
in  scars  during  wet  weather.  The  gradual  change  in  the  color  of  the 
hairs  may  be  caused  either  by  a  diminution  in  the  amount  of  their  pig- 


894 


THE    EXTERNAL    SECRETIONS 


ment  or  by  the  presence  of  minute  air-bubbles  within  their  medulla 
and  fibrous  layer.  These  bubbles  reflect  the  light  very  strongly. 
The  former  change  is  the  usual  cause  of  the  grayness  of  the  hair  in 
old  age,  whereas  its  sudden  turning  gray  is  due  principally  to  the 
formation  of  these  vacuoles. 

Physiologically,  it  is  of  interest  to  note  that  the  adult  human  individual  pro- 
duces about  0.20  gram  of  hair-substance  in  the  course  of  a  day,  but  this  amount 
may  be  greatly  increased  by  heat,  massage,  and  the  cutting  of  the  hair.  Attention 
has  already  been  called  to  the  fact  that  numerous  smooth  muscle  cells  lie  in  relation 
with  the  hairs  which  bridge  over  the  angle  formed  by  the  obliquely  placed  roots 
of  the  latter  and  the  surface  of  the  skin.     The  contraction  of  these  muscle  fibers, 

therefore,  must  lead  to  an  erection  of  the 
hairs  and  the  peculiar  reflex  phenomenon, 
known  as  "goose  flesh."  This  reaction 
most  commonly  arises  in  consequence  of 
local  or  general  stimuli,  such  as  cold,  emo- 
tions, and  irritations  within  the  domain  of 
the  autonomic  nervous  system.  A  few 
cases,  however,  have  been  recorded  which 
show  that  the  pilo-motor  mechanism  may 
be  brought  under  the  control  of  volition.^ 
While  the  question  of  whether  cats  and 
other  animals  are  able  to  erect  their  hairs 
at  will,  cannot  be  decided  definitely,  it 
seems  that  this  reaction  is  not  always 
wholly  reflex  but  embraces  a  strong  ele- 
ment of  volition.  For  the  present,  how- 
ever, it  must  be  placed  in  the  group  of  the 
perception  or  association  reflexes.  The 
sensitiveness  of  the  hairs  which  plays  so 
important  a  part  in  the  sensations  of 
touch,  is  subserved  by  a  ring-like  plexus  of 
nerve  fibrils  surrounding  the  hair-follicle. 
In  the  second  place,  it  should  be  noted 
that  the  contracton  of  these  muscle  cells 
exerts  a  certain  pressure  upon  the  neigh- 
boring sebaceous  glands,  causing  them  to 
discharge  their  oily  secretion  in  greater 
quantities  than  before.  Moreover,  since 
the  ducts  of  these  glands  most  commonly 
empty  directly  into  the  hair-follicles,  a  means  is  provided  to  keep  the  hairs  soft 
and  pliable.  In  the  third  place,  it  should  be  remembered  that  these  scattered 
muscle  cells  play  an  important  part  in  determining  the  vascularity  of  the  skin, 
because  their  contraction  hinders  the  passive  expansion  of  the  capillaries,  thereby 
keeping  the  blood  in  the  deeper  parts  of  the  body,  while  their  relaxation  allows 
the  superficial  capillaries  to  become  injected  with  blood  drawn  from  other  organs 
and  tissues.  Without  doubt,  these  vascular  changes  possess  an  important  bearing 
upon  the  regulation  of  the  body-temperature,  because  the  relaxation  of  the  cuta- 
neous capillaries  invariably  leads  to  a  greater  dissipation  of  heat,  and  vice  versa. 
In  this  connection  brief  mention  should  also  be  made  of  the  fact  that  the  effect 
of  cold  and  warm  baths  upon  the  circulation  is  made  possible  in  part  through  these, 
muscle  cells,  and  in  part  through  the  muscle  cells  of  the  arterioles  themselves. 

The  Skin  as  an  Organ  of  Secretion. — The  sebaceous  glands  are 
simple  acinous  in  character  and  are  usually  found  in  close  relation  with 

1  Maxwell,  Amer.  Jour,  of  Physiol.,  vii,  1902,  369. 


Fig.  487. — Nerve  Terminals  Around 
THE  Root  of  the  Hair  Follicle. 
M,  Medulla;  P,  papilla;  J5,  external 
root  sheath;  J,  internal  root  sheath;  N, 
ramification  of  the  nerve  fiber. 


GROUP  OF  THE  CUTANEOUS  SECRETIONS         895 

the  roots  of  tho  larj^icr  hairs.  Th(nr  (hicts  open  directly  into  their 
sheath.  But  the  otiier  ref!;ioiis  of  the  skin  are  not  free  from  them;  in 
fact,  many  of  them  contain  them  in  large  numbers,  theircxcretory  ducts 
then  openinp;  free  upon  the  surface.  They  are  especially  numerous 
upon  the  forehead,  nose  and  bac^k;  but  are  absent  from  the  volamanus 
and  planta  pedis.  Closely  related  to  these  glands  are  those  of  the  labia 
minora,  glans  penis,  and  prepuce  as  well  as  the  ceruminous  glands  of 
the  external  auditory  meatus.  The  acini  of  these  structures  are 
packed  with  polyhedral  and  flattened  cells  which  divide  and  gradually 
move  outward  in  successive  layers,  where  they  disintegrate  in  the 
oily  semi-liquid  secretion  filling  the  duct.  In  this  way,  a  fatty  ma- 
terial is  formed  which  on  exposure  to  the  air  assumes  a  cheesy  consist- 
ency. When  the  ducts  of  these  glands  become  blocked,  this  material 
undergoes  retrogressive  changes  and  then  forms  a  fertile  medium 
for  the  growth  of  the  ordinary  pus-microbes. 

The  exact  composition  of  this  secretion  is  not  known.  It  contains 
fats,  soaps,  cholcsterin,  albuminous  material,  remnants  of  epithelial 
cells  and  inorganic  salts.  ^  The  cerumen  or  ear-wax  contains  a 
reddish  pigment  and  possesses  a  bitter-sweet  taste.  Similar  materials 
are  the  smegma  prseputii  and  the  fatty  and  odoriferous  secretions  of 
the  anal  and  uropygal  glands  of  many  animals.  The  sebaceous  material 
which  is  generally  found  upon  the  skin  of  the  newborn  infant,  is  known 
as  vernix  caseosa.^  Its  distribution  alone  would  indicate  that  it 
possesses  a  manifold  function.  Thus,  it  may  rightly  be  concluded  that 
it  serves  to  lubricate  the  surface  of  the  skin  and  to  protect  the  hairs 
against  drying.  Moreover,  since  it  is  spread  out  in  an  almost  continu- 
ous layer  across  the  skin,  it  aids  in  retaining  the  body-heat  and  plays, 
therefore,  an  important  part  in  regulating  the  body-temperature. 
This  fact  is  clearly  recognized  by  the  northern  races,  such  as  the  Esqui- 
maux, because  they  carefully  preserve  this  secretion  and  even  inten- 
sify its  action  by  anointing  their  bodies  with  fatty  substances.  In 
the  aquatic  animals  it  serves  a  twofold  purpose,  because  it  protects  them 
against  any  undue  loss  of  heat  and  diminishes  the  friction  between 
their  integument  and  the  water.  Lastly,  the  modified  secretions  of 
the  anal,  uropygal,  and  sexual  glands  of  many  animals  no  doubt  play 
an  important  part  in  the  production  of  the  sexual  reflexes. 

The  sweat-glands  are  simple  tubular  in  character  and  consist  of  a 
coiled  up  portion  which  occupies  the  deeper  layer  of  the  skin,  and  a 
long  winding  duct  which  penetrates  the  corium  and  epidermis  and 
eventually  terminates  in  a  funnel-shaped  enlargement  upon  its  surface.^ 
They  are  found  in  especially  large  numbers  upon  the  palms  of  the 
hands,  the  soles  of  the  feet,  in  the  axilla,  groin  and  upon  the  forehead, 
but  are  absent  from  the  glans  penis,  prepuce  and  the  margins  of  the 

^  Linser  Dissertation,  Tiibingen,  1904. 
2  Zumbusch,  Zeitschr.,  ph.  Chemie,  LIX,  1909,  oOG. 

^  Rabl  (Histology  of  the  Sweat-Glands)  in  Handb.  der  Hautkrankheiten, 
Wien,  1901. 


896 


THE    EXTERNAL    SECRETIONS 


lips.  Their  number  has  been  estimated  at  two  millions^  and  their 
total  secretory  surface  at  1080  m^  The  cells  lining  the  coiled  up 
extremity  of  these  glands  are  columnar  in  shape  and  possess  a  gran- 
ular cytoplasm.  Externally  they  border  upon  a  dense  network  of 
capillaries. 

The  sweat  is  a  clear,  colorless  liquid  of  low  specific  gravity  (1.004).  It  consists 
of  982  parts  of  water  per  1000  c.c;  and  contains  small  quantities  of  salts,  neutral 
fats,  volatile  fatty  acids,  and  traces  of  proteins  and  urea.     The  inorganic  salts  include 

sodium  chlorid  and  small  quantities  of  alkaline 
.sulphates  and  phosphates.  The  latter  impart 
to  it  a  faint  alkaline  reaction,  although  when  first 
.secreted  it  is  prone  to  be  acid,  owing  to  the  pres- 
ence of  a  slight  amount  of  sebaceous  material. 
Profuse  sweating,  however,  may  yield  other  pro- 
teins, such  as  uric  acid,  creatinin,  ethereal  sul- 
phates, phenol,  skatol,  and  albumin. ^  Conse- 
quently, sweating  is  called  for  whenever  the 
activity  of  the  kidneys  is  temporarily  suppressed. 
Mu,scular  exercise  also  tends  to  augment  the  urea 
content  of  the  sweat,  and  in  addition,  gives  rise 
to  an  elimination  of  CO2  which  may  amount  to 
as  much  as  20  grams  per  day.  Under  normal 
conditions,  however,  the  secretion  of  sweat  serves 
merely  as  a  means  of  eliminating  water  and  not 
of  solid  excrements.  While  this  fact  may  be  re- 
garded as  sufficient  reason  to  classify  sweat  as  an 
excretion,  the  use  made  of  it  subsequently  in 
moistening  the  surface  of  the  body  and  in  regulat- 
ing the  body-temperature,  may  prompt  us  to  con- 
sider it  as  a  secretion. 

The  small  quantity  of  sweat  generally 
produced,  evaporates  and  leaves  non-vola- 
tile con.stituents  upon  the  skin,^  but 
naturally,  its  total  quantity  differs  greatly 
with  the  general  condition  of  the  body 
and  the  surroundings.  A  person  dressed 
moderately  warm  may  secrete  as  much 
as  2  or  3  liters  in  a  day,  although  an  out- 
side temperature  which  cau.se s  the  tem- 
perature of  the  skin  to  rise  above  33°C., 
yields  a  much  larger  quantity.  A  part 
of  this  may  be  removed  by  evaporation, 
while  the  remainder  forming  the  so-called  visible  sweat,  is  absorbed  by 
the  clothing  or  is  lost  in  mass.  Naturally,  a  moisture-laden  atmos- 
phere retards  the  evaporation  and  tends  to  produce  a  much  larger 
quantity  of  visible  sweat  than  a  dry  and  warm  atmosphere.  It  should 
also  be  remembered  that  the  secretion  of  sweat  is  closely  correlated 
with  that  of  urine,  because  copious  sweating  most  generally  diminishes 

1  Krause,  Handb.  der  Anatomic,  1879. 

2  Brieger  and  Dieselhorst,  Deutsch.  med.  Wochenschr.,  xxx,  1904,  161. 
'Schierbeck,  Archiv  fur  Anat.  und  Physiol.,  1893,  116. 


Fig.  488.  — Diagrammatic 
Representation  of  the  Hkin, 
Showing  the  Location  of  the 
Sweat  Glands. 

H,  Horny  layer;  L,  stratum 
lucidum;  M,  Malpighian  layer; 
P,  corpuscles  of  Paccini;  PL, 
papillje  of  the  cutis  vera;  C, 
cutis  vera;  S,  sweat  gland;  SC, 
subcutaneous  tissue. 


GROUP  OF  THE  CUTANEOUS  SECRETIONS         897 

the  elimination  of  water  by  the  kidneys,  and  vice  versa.  Both  of 
these  processes  an»  ivhited  in  turn  to  tlie  int(^slinal  secretions,  because 
watery  stools  aiv  invariably  associated  witii  a  diminished  excretion  of 
water  by  the  other  channels. 

The  Innervation  of  the  Sweat-Glands. — The  sweat-glands  are 
richly  supplied  with  nerve  fibers,  some  of  which  are  doubtlessly  secre- 
tory in  their  nature.  They  perforate  the  membrana  propria  and  form 
mulberry-like  end-organs  directly  upon  the  outer  surfaces  of  the  cells. 
According  to  Langley/  those  innervating  the  glands  of  the  cat's 
hind  limb  leave  the  spinal  cord  in  the  first  and  second  lumbar  nerves, 
enter  the  s,\nnpathetic  svstem  and  leave  it  again  in  the  gray  rami 
of  the  sixth  lumbar  to  the  second  sacral  nerves.  Their  chief  outpour- 
ing takes  place  in  the  seventh  lumbar  and  first  sacral  rami.  All  of 
them  enter  into  the  formation  of  the  sciatic  plexus.  A  similar  out- 
pouring occurs  between  the  fourth  and  tenth  thoracic  nerves,  the  fibers 
of  which  eventually  enter  the  brachial  plexus. 

The  presence  of  these  secretory  fibers  has  been  demonstrated  by 
Goltz^  who  stimulated  the  distal  end  of  the  divided  sciatic  nerve  and 
observed  drops  of  sweat  appearing  upon  the  hairless  skin  covering  the 
balls  of  the  feet.  This  effect  may  also  be  evoked  after  the  ligation  of 
the  abdominal  aorta  as  well  as  after  the  amputation  of  the  leg,  but 
naturally,  only  a  very  limited  amount  can  then  be  obtained,  because 
the  cells  are  no  longer  able  to  acquire  new  secretory  material.  Under 
normal  conditions,  this  nervous  mechanism  is  activated  by  rises  in 
the  temperature  of  the  atmosphere  as  well  as  by  increases  in  the  blood- 
pressure  following  muscular  activity  and  increases  in  the  water  con- 
tent of  the  body.  Furthermore,  many  factors  are  constantly  at  work 
which  tend  to  vary  the  amount  and  character  of  this  secretion.  It  is 
a  well  known  fact  that  the  skin  in  fever  is  dry  and  that  the  subsequent 
reappearance  of  the  sweat  is  generally  accompanied  by  a  fall  in  the 
body-temperature.  In  other  words,  a  moist  skin  is  a  favorable  diagnos- 
tic sign,  because  it  facilitates  heat-dissipation.  Profuse  sweating  is 
frequently  associated  with  dyspnea,  nausea  and  psychic  impressions 
of  terror.  Among  the  drugs  which  influence  the  character  of  this 
secretion  should  be  mentioned  pilocarpin  and  atropin.  The  former 
stimulates  its  flow  by  acting  directly  upon  the  terminals  of  the  secre- 
tory nerves,  while  the  latter  diminishes  it  by  paralyzing  these  endings. 
Alcohol  produces  a  dry  skin  and  nicotine  a  moist  skin.  Cold  lessens 
the  secretion,  because  it  gives  rise  to  a  reflex  constriction  of  the  cutan- 
eous blood-vessels. 

The  Mammary  Glands. — Each  fully  formed  mamma  consists  of 
15  to  20  lobes,  which  are  composed  of  lobules  and  the  latter  in  turn  of 
numerous  groups  of  cells  or  acini.  The  smaller  ducts  emerging  from 
these  eventuall}'  unite  into  a  large  lactiferous  duct  which  opens 
through  the  nipple.     Externally  to  their  point  of  union  the  different 

1  Jour,  of  Physiol.,  xii,  1891,  347. 

2  Pfluger's  Archiv,  xi,  1875,  71. 
57 


898  THE    EXTERNAL    SECRETIONS 

lobular  ducts  are  enlarged  into  sinus-like  reservoirs,  which  may  be- 
come highly  distended  during  the  periods  of  active  secretion  of  this 
gland.  The  orifice  of  the  lactiferous  duct  is  invested  by  areolar  tissue 
and  smooth  muscle  fibers,  the  latter  effecting  the  erection  of  the  nipple 
on  reflex  stmiulation.  Around  its  base  winds  a  narrow  zone  of  dark- 
tinted  skin  which  is  beset  with  very  sensitive  papillae  and  contains 
numerous  minute  secretory  glands  of  the  sebaceous  type.  Although 
doubtlessly  belonging  to  the  group  of  the  cutaneous  glands,  it  is 
difficult  to  classify  the  mammse  either  as  modified  sweat-glands  or 
as  sebaceous  glands-.  Their  alveolar  character  as  well  as  the  fatty 
character  of  their  secretion,  might  prompt  us  to  homologize  them  with 
the  latter,  but  since  their  secretory  cells  are  short  columnar  in  outline 
and  are  arranged  in  a  single  row,  they  really  present  a  much  closer 
resemblance  to  the  former.  Their  size,  number,  and  position  vary 
greatly  in  different  mammals.  In  man,  they  are  placed  one  upon 
each  side  of  the  anterior  aspect  of  the  thorax  and  are  copiousty  supplied 
with  blood-vessels,  l^miphatics  and  nerves. 

The  histological  character  of  these  glands  varies  considerably 
and  especially  during  pregnancy  and  lactation.  When  milk  is  first 
formed,  the  epithelium  of  the  alveoli  becomes  sharply  differentiated 
from  that  of  the  ducts.  While  the  lining  of  the  latter  remains  cub- 
oidal  in  shape,  that  of  the  former  becomes  elongated  toward  the  lumen, 
and  shows  a  proliferation  of  the  nuclei  as  well  as  numerous  new  granules 
and  fat-globules.  This  state  is  soon  followed  by  one  of  active  secre- 
tion. The  cells  then  enlarge  still  further  and  project  markedh'  into 
the  lumen  of  the  acini.  Fat-droplets  now  appear  in  much  greater 
numbers,  while  the  granules  which  during  the  early  secretory  period 
presented  a  spherical  outline,  are  now  elongated  and  spiral  in  shape.  ^ 
A  part  of  the  inner  segment  of  each  cell  then  disintegrates,  its  fragments 
being  forced  into  the  duct.  This  fully  explains  the  fact  that  the  early 
secretion  invariably  embraces  many  epithelial  cells  which  are  only 
partly  transformed,  and  are,  therefore,  known  as  colostrum  corpuscles.^ 
The  places  previously  occupied  by  these  fragmented  cells,  are 
again  taken  up  by  new  ones  formed  by  karyokinetic  division  from 
neighboring  cells.  In  many  cases,  however,  the  ruptured  inner  part 
of  the  cell  is  again  closed,  whereupon  the  cj-toplasm  is  slowly  lefonned. 

During  pregnancy,  the  mammae  enlarge  and  become  firm  and  ten- 
der to  the  touch.  Their  blood-supply  then  increases  enormously,  as 
is  evinced  particularly  bj'^  the  formation  of  prominent  plexuses  of 
veins.  The  areola  investing  the  base  of  the  nipple,  becomes  broader 
and  darker  in  color  and  shows  very  prominent  papillae.  The  nipple 
itself  increases  materially  in  size.  Evidentlv,  these  macroscopic 
changes  find  their  origin  in  a  gradual  proliferation  of  the  secretory 
cells  and  the  formation  of  many  new  acini.  This  process  of  evolution 
begins  soon  after  conception  and  does  not  cease  until  shortly  after 

1  Steinhaus,  Archiv  fiir  Physiol.,  1892,  54. 

2  Heidenhain,  Hermann's  Handb.  der  Physiol.,  1883. 


GROUP  OF  THE  CUTANEOUS  SECRETIONS         899 

the  birth  of  the  yoiiiip;.  The  flow  of  milk,  however,  does  not  commence 
as  a  rule  until  labor  has  been  comjjleted;  in  fact,  in  woman  it  does  not 
begin  until  24  or  48  hours  afterward,  but  its  onset  may  Ijc  considerably 
hastened  by  the  mechanical  stimulation  of  the  mammae.  In  woman  the 
duration  of  the  period  of  lactation  varies  from  a  few  days  to  almost  a 
year,  but  much  depends  upon  their  general  condition  and  the  stimuli 
to  which  they  have  been  subjected.  Inasmuch  as  the  onset  of  a  new 
pregnancy  brings  this  secretion  to  a  close,  lactation  is  frequently  made 
to  continue  by  artificial  means  in  order  to  prevent  a  new  conception, 
but  this  practice  fails  in  most  instances  to  have  the  desired  effect. 
Lactation  having  been  completed,  the  glands  involute,  i.e.,  they  under- 
go retrogressive  changes  which  finally  lead  to  the  establishment  of  the 
normal  histological  picture  of  the  resting  organ. 

The  Imiervation  of  the  Mammary  Glands. — Since  the  mammary 
glands  do  not  seem  to  be  in  possession  of  secretory  nerves,  we  cannot 
help  being  astounded  at  the  close  adaptation  of  the  activity  of  these 
organs  to  the  condition  of  the  developing  young.  Thus,  we  find  that 
the  mammae  begin  to  grow  very  shortly  after  conception  and  continue 
their  growth  until  the  birth  of  the  young.  With  surprising  exactitude 
the  milk  pours  forth,  not  to  cease  until  the  end  of  the  period  lactation, 
i.e.,  about  six  to  nine  months  thereafter.  The  only  condition  for  it 
is  to  remove  it  regularly — preferably  in  a  normal  way  by  the  process 
of  suckling.  Obviously,  we  are  dealing  here  with  a  most  remarkable 
transfer  of  function,  because  while  the  fetus  abstracts  its  nutritive 
material  directly  from  the  mother's  blood  with  the  help  of  the  placenta, 
the  infant  derives  its  nutritive  material  entirely  from  the  mammae. 
But  this  change  is  not  at  all  detrimental  to  the  young,  because  milk  is 
a  preparation  which  is  accurately  adapted  to  its  assimilative  and 
dissimilative  power. 

The  progressive  character  of  the  development  of  the  mammae  sug- 
gests that  it  is  controlled  by  some  mechanism  which  in  turn  is  in- 
fluenced by  the  sexual  organs.  Regarding  this  point,  v/e  have 
the  positive  experimental  evidence  that  extracts  of  corpus  luteum  of 
the  ovary  and  of  the  developing  uterus  give  rise  to  an  active  growth 
of  the  mammae  even  in  non-pregnant  animals.^  Secondly,  we  shall  see 
later  that  the  internal  secretion  of  the  pituitary  body  possesses  a  pro- 
nounced excitatory  influence  upon  the  flow  of  milk,  but  while  it  seems 
to  have  been  definitely  established  that  the  aquisition  of  the  full 
functional  power  of  the  mammae  is  controlled  by  chemical  stimuli  of 
the  type  of  the  hormones,  it  cannot  be  denied  that  a  reflex  nervous 
factor  is  at  work.  Thus,  it  has  been  found  that  the  stimulation  of 
sensory  nerves  is  followed  by  a  diminution  in  the  amount  of  this  secre- 
tion and  that,  in  woman,  the  period  of  lactation  may  be  cut  short  by 
strong  emotions,  epileptic  seizures,  and  other  general  functional  dis- 
turbances. Moreover,  this  influence  may  be  reciprocal,  because  the 
artificial  suppression  of  this  secretion  may  have  deleterious  effects  upon 

1  Lane-Claypon  and  Starling,  Proc.  R.  Soc,  1906,  and  Hammond,  ibid.,  1917. 


900  THE  EXTERNAL  SECRETIONS 

the  health  of  the  woman.  In  this  connection,  it  is  also  of  interest  to 
note  that  the  act  of  suckling  excites  tonic  contractions  of  the  uterus,  a 
means  commonly  employed  to  cause  this  organ  to  assume  its  former 
shape  after  labor,  and  especially  when  this  involution  is  slow  and  is 
associated  with  hemorrhage.  It  should  also  be  noted  that  the  secre- 
tion of  milk  is  not  exclusively  a  function  of  the  pregnant  female, 
because  many  cases  are  on  record  of  men  and  boN^s  possessing  well 
developed  and  actively  secreting  mammae.  It  had  also  been  observed 
that  virgin  bitches  may  produce  milk  and  that  sterile  mules  may 
yield  sufficient  rnilk  to  suckle  a  foal. 

Properties  of  Milk. — "When  the  mammae  fii'st  begin  to  discharge 
their  secretion,  they  do  not  yield  pure  milk  but  a  peculiar  fluid  which 
is  known  as  colostrum.  A  few  drops  of  this  secretion  may  usually  be 
obtained  within  a  short  time  after  the  completion  of  labor  by  gently 
massaging  the  breasts  in  the  direction  of  the  nipples.  Its  total  amount, 
however,  is  never  considerable  although  it  flows  more  freely  later  on. 
As  has  been  stated  above,  this  material  is  gradually  flushed  out  of  the 
ducts,  giving  wa}'  in  the  course  of  two  or  three  days  to  pure  milk. 
To  begin  with,  the  colostrum  appears  as  drops  of  a  watery  and  usually 
very  cloudy  fluid,  possessing  a  specific  gravity  of  1.040  to  1.080.  In 
larger  quantities  it  exhibits  an  opalescent,  yellowish  appearance,  and 
gives  rise  to  a  coagulum  of  similar  color.  The  pigment  to  which  the 
latter  is  due,  is  contained  in  its  fatty  admixtures.  "UTien  examined 
under  the  microscpoe,  it  is  seen  to  contain  numerous  fat-globules  and 
fragmented  cells,  among  which  are  many  leukocj-tes  which  have 
migrated  and  have  become  loaded  with  fat-droplets.  Colostrimi 
yields  little  or  no  casein  but  about  3  per  cent,  of  proteins,  consisting 
of  coagulable  lactalbumin  and  lactoglobulin.  Moreover,  while  it  con- 
tains as  much  fat  as  the  pure  milk  secreted  subsequently,  it  embraces 
somewhat  greater  quantities  of  lactose  and  salts.  Colostrmn  is  na- 
ture's laxative,  and  hence,  the  infant  should  be  allowed  to  partake  of 
it  freeh'. 

The  milk,  following  the  colostrum,  is  an  opaque  fluid,  possessing  a  yellowish 
white  or  bluish  white  appearance  according  to  its  concentration.  It  possesses  a 
sweetish  taste  and  a  very  characteristic  odor.  Its  specific  gra^■^ty  varies  between 
1.026  and  1..036,  the  highest  values  being  generally  obtained  only  in  well  nour- 
ished women.  It  is  neutral  to  litmus,  alkaline  to  lacmoid,  and  acid  to  phenol- 
phthalein.  ^^^len  examined  under  the  microscope,  it  is  seen  to  consist  of  a  watery 
part,  or  milk-plasma  and  numerous  fat-globules,  or  milk-corpuscles.  The  diameter 
of  the  latter  varies  between  1/x  and  6ju.  Here  and  there  we  also  recognize 
fragmented  epitheUal  cells,  leukocytes  and  nuclear  material.  Milk,  therefore,  is 
essentialh-  an  emulsion  of  fat,  the  opaque  appearance  of  which  is  due  to  the  diffuse 
reflection  of  the  light  by  these  globules.  On  standing,  these  droplets  of  fat  rise 
to  the  surface,  owing  to  their  lesser  specific  gravity,  and  form  the  cream.  By 
mechanical  agitation  the  latter  may  be  made  to  coalesce  to  form  butter.  This  fact, 
that  it  requires  agitation  to  coalesce  the  fat-globules,  has  been  the  subject  of  much 
stud}'.  Thus,  it  has  been  shown  that  the  globules  in  cow's  milk  are  invested 
by  a  mucous-like  envelope,  which  must  first  be  broken  up  before  the  fat  can  run 
together.  In  addition,  it  has  been  assumed  that  the  globules  in  other  types  of  milk 
are  surrounded  by  a  haptogen  membrane  which  is  formed  of  the  proteins  of  the 


GROUP  OF  THE  CUTANEOUS  SECRETIONS 


901 


cell  from  which  they  have  been  derived,  but  it  seems  scarcely  necessary  to  make 
this  assumption,  because  sucli  an  investment  mi^ht  more  easily  result  in  conse- 
quence of  the  molecular  attraction  of  the  fat  for  the  neif^hboring  protein  particles.' 
If  milk  is  boiled,  a  "skin"  is  formed  upon  its  surface,  which  consists  of  lactal- 
bumin,  casein  and  calcium  salts.  Furthermore,  when  exposed  to  the  air,  milk 
undergoes  a  peciUiar  fermentation  in  consequence  of  the  entrance  of  micro-organ- 
isms, chief  among  which  is  the  bacillus  lacticus.  Its  reaction  then  changes  to  sour, 
owing  to  the  formation  of  lactic  acid  from  lactose.  Milk  may  also  undergo 
alcoholic  ferment  alio  n.  Wliile  this  change  is  not  easily  effected  by  means  of  yeast 
cells,  it  is  readily  brought  about  by  fungoid  growths.  The  milk-sugar  is  converted 
into  glucose  and  galactose  and  the  latter  into  alcohol  and  carbonic  acid.  In  this 
way,  such  preparations  as  Koumiss  and  Kephir  have  been  derived.  The  coaqula- 
tion  of  milk  is  usually  brought  about  by  means  of  rennin,  an  enzyme  contained  in 
the  gastric  juice  of  mamnuils.  The  clot,  or  curd,  consists  of  casein  and  entangled 
fat-droplets,  while  the  fluid  residue,  or  whey,  embraces  sugar,  salts,  albumin  and  a 
newly-formed    protein    called    whey-protein. 

The  Composition  of  Milk. — The  formation  of  milk  depends  not 
only  upon  the  condition  of  the  mother  but  also  upon  that  of  the  infant. 
A  robust  woman,  especially  a  multipara,  may  yield  a  large  enough 
quantity  to  feed  half  a  dozen  infants,  but  naturally,  the  true  physio- 
logical measure  is  the  amount  which  is  required  for  the  wellfare  of  a 
single  infant,  weighing,  say,  3000  to  3500  grams.  These  requirements 
are  compiled  in  the  succeeding  table : 


1  day 20 

2  days 75 

3  days 168 

4  days 252 

5  days 303 

6  days 353 

Required  by  infant  ■"  7  days 367 

2  weeks 472 

3  weeks 512 

4  weeks 512 

5  weeks 577 

6  weeks 613 

7  weeks 691 


grams 
grams 
grams 
grams 
grams 
grams 
grams 
grams 
grams 
grams 
grams 
grams 
grams 


A  comparison  of  these  data  with  those  now  following  shows  conclu- 
sively that  the  average  woman  furnishes  an  ample  supply  of  milk, 
and  that  the  quantity  secreted  increases  steadily  as  demanded  by  the 
growth  of  the  infant,  until  about  the  28th  week,  when  its  amount  di- 
minishes up  to  the  end  of  the  period  of  lactation. 


Secreted  by  mother 


1  day 20  grams 

2  days   97  grams 

3  days •. 211  grams 

4  days 326  grams 

5  days 364  grams 

6  days 402  grams 

7  days 478  grams 

1  week 502  grams 

'  Hammarsten,   Lehrb.   der   physiol.    Chemie,    1907,   und    Raudnitz,    Ergebn. 
der  Physiol,  ii,  1903. 


Secreted  by  mother 


902  THE  EXTERNAL  SECRETIONS 

3-4  weeks 572  grams 

5-8  weeks 736  grams 

9-12  weeks 797  grams 

13-16  weeks 836  grams 

17-20  weeks 867  grams 

21-24  weeks 944  grams 

25-28  weeks 964  grams 

29-32  weeks 916  grams 

33-36  weeks 909  grams 

37  weeks 885  grams 

The  fats  of  milk  are  similar  to  those  contained  in  adipose  tissue.  Their  propor- 
tion may  be  given  as  follows:  olein,  ^'j,  palmitin,  J.3;  stearin,  ^;  butyrin,  caproin, 
and  caprylin,  3^4.  In  milk-plasma  are  found  various  proteins,  a  carbohydrate, 
lactose,  inorganic  salts  and  a  small  amount  of  lecithin  and  nitrogenous  extractives. 
The  principal  protein  is  called  caseinogen.  It  belongs  to  the  group  of  the  phos- 
phoproteins  and  may  be  precipitated  by  acids,  such  as  acetic  acid,  or  by  saturation 
with  magnesium  sulphate,  or  half-saturation  with  ammonium  sulphate.  Rennin 
causesit  to  coagulate  with  the  formation  of  casein.  This  process  is  employed  in  the 
preparation  of  cheese,  the  curd  consisting  of  casein  and  entangled  fat-globules. 
If  this  coagulated  mass  is  allowed  to  stand,  milk-serum  separates  from  it.  The 
latter  contains  two  other  proteins,  namely,  lactalbumin  and  lactoglobulin.  The 
carbohydrate  is  milk-sugar  or  lactose,  a  disaccharide  of  the  composition:  C12H22O11. 
When  hydrolized  it  takes  up  water  and  galactose: 

C12H22H11  +  H2O  =  C6H12O6  +  C6H12O6 

It  may  be  also  be  found  in  the  urine  of  woman  during  the  early  days  of  lactation, 
when  there  is  a  reabsorption  of  the  lactose  owing  to  an  insufficient  withdrawal 
of  the  milk.  For  the  same  reason,  it  may  enter  the  urine  during  and  after  the  period 
of  weaning.  It  then  gives  the  ordinary  tests  for  reducing  sugar.  The  salts  of 
milk  consist  of  calcium  phosphate,  a  small  quantity  of  magnesium  phosphate  and 
the  chlorids  of  sodium  and  potassium.  Especially  marked  is  the  richness  of 
milk  in  calcium,  phosphorus,  and  magnesium,  as  compared  with  the  blood-serum. 
This  is  of  greatest  importance  for  the  growth  of  the  bones,  while  the  growth  of  the 
tissues  necessitates  potassiiim  rather  than  sodium.  At  all  events,  it  is  a  most 
striking  fact  that  these  cells  are  capable  of  selecting  from  the  fluids  of  the  body 
only  those  salts  which  are  of  greatest  use  to  the  developing  young.  This  selective 
action  they  also  display  in  the  formation  of  caseinogen  and  lactose,  both  of  which 
do  not  exist  as  such  in  the  blood  or  lymph.  It  is  by  means  of  this  concentration  of 
materials  of  the  proper  kind  that  the  rabbit  is  enabled  to  double  its  weight  in  six 
days,  the  dog  in  96  days,  and  the  infant  in  108  days. 

The  practical  importance  of  these  brief  chemical  data  becomes 
apparent  immediately  if  a  substitute  must  be  sought  for  human  milk.-^ 
Although  other  types  of  milk  are  more  like  human  milk,  we  are  then 
accustomed  to  use  cow's  milk,  because  it  is  most  easily  procured.  Its 
composition,  however,  is  very  unlike  that  of  human  milk,  as  the 
following  tabulation  will  show: 

Human  Cow's 

Water 87.16  87.10 

Fat 4.28  4.20 

Casein 1.04  3.25 

Sugar 7.40  5.00 

Ash 0.10  0.52 

1  Voltz,  in  Oppenheimer's  Handb.  der  Biochemie,  1910,  iii,  382. 


THE    LYMPHATIC    AND    MUCOUS    SECRETIONS  903 

The  most  important  differences  may  ho  l)riofly  summarized  as  fol- 
lows: 

(a)  Appearance.  Cow's  milk  is  white  in  color  and  opaque,  while  human  milk 
is  more  translucent  and  possesses  a  yellowish  or  bluish  hue  in  accordance  with  its 
concentration. 

(b)  Ilcaction.     Cow's  milk  is  acid,  while  human  milk  is  alkaline, 

(c)  Specific  gravity.     Cow's  milk:  1.030-1.035;  human  milk:  1.024-1.035, 

(rf)  Character  of  the  curd.  Rennet  produces  with  cow's  milk  a  dense  and  firm 
coaRulum  which  is  not  easily  digested,  while  human  milk  yields  under  the  same 
circumstances  a  light,  flocculent  and  easily  digestible  clot. 

(e)  Histological  character.  The  fat-globules  of  cow's  milk  are  invested  by  a 
relatively  thick  albuminous  envelope. 

(/)  Bacteriological  character.  Human  milk  is  in  a  practically  sterile  condition 
when  withdrawn  from   the  breast. 

Those  differonces  in  the  chemical  composition  and  reaction  must 
first  be  removed  by  diluting  cow's  milk  to  reduce  the  casein  and  by 
adding  to  it  cream  and  milk-sugar,  making  the  whole  alkaline  in  re- 
action. The  danger  of  microbic  infection  of  cow's  milk  may  be  obvi- 
ated by  pasteurization,  i.e.,  by  subjecting  the  milk  to  a  temperature  of 
167-175°F.  which  sterilizes  it,  but  does  not  impair  its  nutritive  value. 
The  following  formula  may  be  employed  as  a  sample : 

Top  milk 5  drams 

Water 5  drams 

Lime  water 1  dram 

Sugar  of  milk 20  grains 

But  this  "hmnanized"  cow's  milk  cannot  be  regarded  as  a  perfect 
substitute  for  natural  mother's  milk.  Undoubtedly,  there  are  also 
certain  other  differences  present  which  the  chemist  has  not  detected  as 
yet.  As  one  of  these  might  be  mentioned  the  qualitative  differences 
between  the  caseinogen  of  different  types  of  milk. 


CHAPTER  LXXVII 
THE  LYMPHATIC  AND  MUCOUS  SECRETIONS 

The  Spleen. — Since  this  organ  possesses  the  characteristics  of 
lymphatic  tissue  and  has  not  been  proved  to  furnish  an  internal  se- 
cretion, it  may  properly  be  considered  under  the  heading  of  the  lym- 
phatic glands.  It  is,  of  course,  a  ductless  organ  and  belongs  to  the 
group  of  the  hemal  bodies  which  are  distinguished  from  the  ordinary 
lymphatic  glands  by  their  red  color  and  by  the  fact  that  their  sinuses 
contain  only  blood.  Histologically  it  is  of  importance  for  us  to  re- 
member that  it  is  enveloped  by  a  capsule  of  fibrous  tissue,  containing 
elastic  fibers  and  smooth  muscle  cells.  Numerous  septa  or  trabeculae 
extend  from  its  inner  surface  into  the  interior  of  the  organ  which  they 


904  THE    EXTERNAL    SECRETIONS 

subdivide  into  compartments  containing  the  spleen  pulp.  The  latter 
is  dark  red  or  reddish-brown  in  color  and  is  composed  chiefly  of  cells 
embedded  in  a  ground  substance  of  fibers  and  the  prolongations  of  large 
nucleated  cells.  Some  of  the  latter  greatly  resemble  lymph-corpuscles, 
while  others  contain  a  pigment  which  is  closely  allied  to  the  hemo- 
globin of  the  red  blood  corpuscles.  Scattered  through  the  pulp  are 
many  red  corpuscles  and  the  fragments  derived  from  them.  The 
blood-vessels  enter  and  leave  this  gland  at  the  hilus  and  remain  at  first 
confined  to  the  trabeculae.  Eventually,  however,  they  terminate  in 
a  network  of  capillaries  in  the  pulp,  their  endothelial  lining  becoming 
continuous  with  that  of  the  rete  of  the  latter.  The  sheaths  of  these 
minute  arteries  are  beset  with  rounded  bodies,  the  so-called  Malpigh- 
ian  corpuscles,  the  structure  of  which  is  practically  identical  with  that 
of  a  hmiph  nodule.  The  veins  also  begin  as  opened  tubules.  Conse- 
quently, it  will  be  seen  that  the  cellular  elements  of  the  splenic  pulp 
are  in  actual  contact  with  the  blood  and  not  with  the  h^mph,  as  is  the 
case  in  other  organs.  This  arrangement  enables  the  blood  to  be  poured 
out  directly  into  the  interstitial  spaces  of  this  organ. 

The  Fimction  of  the  Spleen. — Since  the  removal  of  this  organ  is 
not  followed  by  serious  consequences,  the  conclusion  seems  justified 
that  it  does  not  furnish  an  internal  secretion  which  is  essential  to  life. 
In  fact,  the  symptoms  of  splenectomy  are  transient  in  their  nature 
and  betray  themselves  in  an  anemia,  a  greater  cholesterol  content 
of  the  blood,  and  a  greater  resistance  to  hemolytic  agents.^  Further- 
more, it  is  possible  to  transplant  this  organ  into  the  subcutaneous 
tissues,  but  the  growth  of  these  transplants  is  not  assured,  unless  the 
animal  is  still  young  and  is  not  in  possession  of  left-over  splenic  tissue. 
In  other  words,  the  transplanted  portion  is  more  prone  to  degenerate 
if  a  portion  of  the  spleen  has  been  left  in  the  body  or  if  the  animal  has 
reached  a  stage  of  its  life  when  the  function  of  this  organ  is  no  longer 
absolutely  essential,  because  its  loss  may  then  be  more  easily  compen- 
sated for  by  the  other  Ijmiphatic  tissues. ^  These  facts  strongly  point 
toward  the  presence  of  a  hormone  which  stimulates  the  growth  of. the 
transplant. 

In  the  absence  of  more  positive  results  following  the  removal  of 
this  organ  and  in  view  of  its  characteristic  Ijnnphatic  structure,  it 
may  be  assumed  that  it  is  engaged  in  the  formation  of  white  blood 
corpuscles.  This  assumption  is  correct,  because  it  has  been  shown  that 
the  blood  of  the  splenic  vein  contains  large  nmnbers  of  hmiphocytes. 
Secondly,  it  is  a  well-known  fact  that  the  disease,  known  as  leucocy- 
themia,  in  which  the  nmnber  of  the  white  cells  is  greatly  increased,  is 
invariably  associated  with  an  enlargement  or  hypertrophy  of  this  or- 
gan. Large  numbers  of  these  cells  may  then  be  released  from  his 
organ  by  causing  it  to  contract  bj^  means  of  an  electric  current  applied 
to  the  neighboring  abdominal  wall. 

1  Karsner  and  Pearce,  Journ.  Exp.  Med.,  xvi,  1912,  769. 
^  Manely  and  Marine,  Jour.  Exp.  Med.  xxv,  1917,  619. 


THE    LYMPHATIC    AND    MUCOUS    SECRETIONS  905 

It  has  also  boon  ostaI)iislu'(l  thai  in  cinhiyonal  life  t,li(>  spleen  pos- 
sesses the  function  of  a  henialopoicMic.  oi-fj;an  and  that  ijs  i)o\ver  of  form- 
ing corpuscles  may  l)e  called  into  phiy  during  adult  life  whenever 
requii-ed.  In  fact,  it  seems  to  retain  this  function  during  the  entire  life 
of  some  animals,  because  it  embraces  cells  which  display  all  the  charac- 
teristics of  the  hematoblasts  of  the  bom^  marrow.  In  these  animals,  the 
removal  of  the  spleen  gives  rise  to  a  hypertrophy  of  the  bone  marrow. 

The  spleen  is  one  of  the  organs  in  which  the  red  corpuscles  of  the 
blood  undergo  disintegration.  This  inference  is  based  upon  the  fact 
that  the  pulp  contains  an  abundance  of  these  cells  in  varying  stages  of 
degeneration.  This  statement,  however,  is  not  meant  to  imply  that 
this  organ  is  the  chief  place  in  which  the  red  corpuscles  are  destroyed, 
nor  that  their  disintegration  actually  leads  to  a  liberation  of  their  color- 
ing material,  the  hemoglobin.  More  plausible  is  the  view  which  holds 
that  the  spleen  merely  accomplishes  the  fragmentation  of  the  worn 
out  corpuscles  which  are  then  more  fully  reduced  in  the  liver.  Un- 
der pathological  conditions,  however,  its  destructive  power  may  be 
greatly  increased,  as  is  proved  by  the  fact  that  it  then  becomes  a 
depository  for  iron  which  can  only  be  derived  from  the  red  corpuscles. 
Such  a  condition  is  developed  in  the  course  of  the  disease,  known  as 
pernicious  anemia.  It  has  also  been  demonstrated  that  the  spleen 
aids  in  the  formation  of  uric  acid,  because  the  removal  of  the  kidneys 
gives  rise  to  an  accumulation  of  this  substance  within  this  organ. 

Attention  has  previously  been  called  to  the  spongy  character  of  the 
pulp  of  the  spleen  which  enables  this  organ  to  accommodate  enormous 
quantities  of  blood.  With  the  help  of  the  smooth  musculature  of  its 
capsule  and  trabeculaB,  this  blood  is  again  returned  into  the  general 
circulation.  For  this  reason,  it  may  be  conjectured  that  this  organ 
acts  as  a  vascular  reservoir  or  diverticulum  for  the  digestive  organs  or 
the  portal  circulation.  Its  smooth  musculature  is  innervated  by 
fibers  which  closely  invest  Ihe  splenic  arteries  and  are  derived  from  the 
celiac  ganglion  of  the  solar  plexus.  In  this  way,  the  spleen  is  brought 
into  correlation  not  only  with  the  other  portal  organs  but  also  with 
the  central  nervous  system.  Stimulation  of  these  nerves  evokes  a 
vaso-constrictor  reaction  which  prevents  the  arterial  blood  from 
entering  the  spleen,  while  its  venous  tubules  are  emptied.  The 
division  of  these  nerves,  on  the  other  hand,  gives  rise  to  an  engorge- 
ment of  this  organ  and  a  withdrawal  of  a  considerable  quantity  of  blood 
from  the  general  circulation.  Of  special  interest  is  the  fact  that  these 
alterations  in  its  vascularity  may  also  result  in  consequence  of  reflex 
stimulation;  in  fact,  Roy"^  and  others  state  that  they  appear  with 
almost  rhythmic  regularity  at  the  rate  of  one  in  about  every  minute. 
Since  the  mechanical  effect  of  these  ordinary  wave-like  contractions 
upon  the  general  circulation  cannot  be  considerable,  they  must  be  more 

1  Jour,  of  Physiol.,  iii,  1881,  203,  also  Schaefer  and  Moore,  Jour,  of  Physiol., 
XX,  1896. 


906  THE  EXTERNAL  SECRETIONS 

especially  concerned  with  a  periodic  renewal  of  the  blood  filling  the 
splenic  spaces. 

The  Tonsils. — The  faucial  tonsils  consist  of  two  globular  masses 
of  lymphoid  tissue  placed  in  the  recesses  between  the  palatal  arches. 
Although  originally  developed  in  two  lobes,  an  upper  and  a  lower,  this 
demarcation  disappears  shortly  before  birth  and  the  entire  organ  then 
appears  as  a  nearly  spherical,  slightly  flattened  disc  which  is  attached 
to  the  floor  of  the  tonsillar  sinus  by  a  root  consisting  of  tonsillar  tissue 
and  a  fibrous  investment.  The  latter,  in  fact,  spreads  over  its  entire  at- 
tached surface  and  becomes  continuous  with  the  fibrous  layer  of  the 
neighboring  mucous  membrane.  A  nuinber  of  membranous  septa 
extend  from  its  surface  into  the  substance  of  this  organ,  subdividing  it 
into  a  number  of  lobules.     Its  outer  surface  is  covered  with  epithelium. 

The  crypts  of  the  tonsil  may  be  single  or  branched.  In  the  former 
case,  they  retain  a  rather  uniform  diameter  throughout  their  course, 
while  in  the  latter,  their  outer  portions  are  much  narrower  than  their 
inner.  They  are  directed,  as  a  rule,  in  a  straight  line  toward  the  sur- 
face and  show  no  contents  with  the  exception  of  irregular  accumula- 
tions of  cellular  debris.  Consequently,  the  capsule  of  the  tonsil  with 
its  trabeculse  forms  an  inverted  replica  of  the  epithelium  in  which 
are  situated  the  blind  ends  of  the  crypts.  A  thin  layer  of  lymphoid 
tissue  surrounds  their  basal  portions,  whence  it  extends  outward  and 
divides  the  different  crypts  into  several  colonies.^ 

The  Function  of  the  Faucial  Tonsils. — The  tonsils  reach  their 
highest  development  in  the  mammals  in  which  they  show  a  steady 
growth  early  in  life.  They  atrophy  later  on.  Regarding  their  func- 
tion we  know  little,  the  only  definite  conclusion  beingthat  they  play  the 
part  of  a  hematopoietic  tissue.  This  inference  seems  justified  in  view 
of  their  Ijanphoid  structure.  Many  of  the  lymphocytes  produced  in 
the  genninal  centers  of  their  follicles  find  their  way  through  the  epithe- 
lium into  the  crypts,  where  they  help  in  the  formation  of  the  cheesy 
masses  so  often  found  in  these  ducts.  A  certain  number  of  them  also 
enter  the  general  efferent  lymphatics  of  the  neck.  It  is  a  suggestive 
fact  that  the  tonsil  attains  is  greatest  activity  during  the  early  years 
of  life,  when  the  body  is  still  growing  and  is  greatly  in  need  of  large 
nmnbers  of  white  corpuscles.  It  will  be  remembered  that  the  other 
lymphoid  nodules  are  at  this  time  similarly  active.  Consequently,  the 
tonsils  merely  participate  in  a  general  function  and  the  part  played 
by  them  may  readily  be  compensated  for  by  other  lymphoid  tissues. 
These  facts  tend  to  show  that  a  mild  degree  of  hypertrophy  of  the 
tonsils  is  to  be  expected  in  early  youth  and  that  the  removal  of  these 
organs  should  not  be  advocated  unless  their  size  and  condition  leads 
to  such  symptoms  as  impaired  breathing,  and  an  interference  with  the 
voice  and  movability  of  the  palate. 

The  preceding  deduction  may  be  employed  as  a  means  of  disposing 

^  Barnes,  The  Tonsils,  Faucial,  Lingual  and  Pharyngeal,  St.  Louis,  1914. 


THE    LYMPHATIC    AND    MUCOUS    SECRETIONS 


907 


of  the  assumption  that  the  tonsils  give  riso  to  an  internal  secretion.^ 
The  fact  that  the  now  extensively  practised  eniu^leation  of  these  organs 
does  not  produce  untoward  symptoms  should  be  sufficient  to  prove 
this  point.  Those  investigators  who  nevertheless  adhere  to  the  con- 
trary contention,  must  admit  that  this  secretion  cannot  be  specific, 
but  must  Ix^  common  to  all  the  lymphoid  tissues  so  that  the  activity  of 
the  tonsils  may  be  compensated  for  by  other  structures.  A  thii'd  con- 
tention is  that  these  organs  protect  the  organism  against  bacterial  in- 
vasion. This  assumption  is  in  accordance  with  the  general  conception 
that  lymphoid  nodules  act  as  sieves  and  catch  the  infectious  particles 
in  their  meshes.  While  it  cannot  be  denied  that  the  tonsils  possess 
an  influence  of  this  kind,  it  is  also  true  that  they  form  a  relatively 
open  connection  between  the  cavity  of  the  mouth  and  the  lymphatics 
of  the  neck  and  may,  therefore,  rather  invite  in- 
fection than  prevent  it.  In  fact,  tonsillectomy  is 
frequently  practised  to  do  away  with  this  possible 
source  and  path  of  infection,  and  especially  if 
these  organs  have  been  the  seat  of  inflammation 
(tonsillitis)  and  are  in  part  disintegrated.  These 
cases  are  usually  benefited  by  tonsillectomy,  but 
naturally,  this  is  not  a  sufficient  reason  to  con- 
demn the  tonsils  as  perfectly  useless  organs  and 
to  advocate  their  removal  as  soon  as  they  rise 
above  the  margins  of  the  faucial  pillars. 

The  Lingual  and  Pharyngeal  Tonsils. — The 
Ungual  tonsil  consists  of  a  variable  number  of 
lymphoid  nodules  arranged  along  the  base  of  the 
tongue  next  to  the  median  line.     The  pharyngeal        ^         „„     ^ 

° ,  ,         .  ,    .  .      .,  r  1  u    •  I  Fig.    489.— Goblet 

tonsil  or  adenoid  is  a  similar  mass  oi  lymphoid  c^lls  Showing  the  Ac- 
tissue  which  is  suspended  from  the  vault  of  the  cumulation  and  Dis- 
naso-pharynx  immediately  behind  the  nasal  ^^^^^^^^  "'^  Mucous 
choanse.  Smaller  depositions  are  found  upon  the 
posterior  and  lateral  walls  of  the  pharynx.  Their  histological  char- 
acter is  practically  identical  with  that  of  the  faucial  tonsil,  and  so  is 
their  function. 

The  Mucous  Glands  and  Their  Secretory  Product. — A  large 
number  of  small  glandular  bodies  are  found  in  the  mouth  and  aUmen- 
tary  canal  which  furnish  a  very  viscous  and  stringy  secretion.  This 
quahty  is  imparted  to  it  by  a  special  constituent,  the  mucin.  In 
accordance  with  their  distribution,  these  glands  may  be  classified  as 
buccal,  palatinal  and  lingual.  Their  structure  is  practically  identical 
with  that  of  a  simple  tubular  gland,  possessing  large  and  clear  lining 
cells.  Obviously,  the  function  of  this  viscous  secretion  is  to  lubricate 
the  mucous  surfaces. 

A  very  good  illustration  of  the  action  of  a  mucous  gland  is  furnished 

1  Massini,  Int.  Secretion  of  the  Tonsil,  New  York  Med.  Jour.,  1898,  and  Scheier, 
Berliner  Laryngol.  Gesellsch.,  1903. 


908  THE    EXTERNAL    SECRETIONS 

by  the  goblet  cells  with  which  the  epithelial  lining  of  the  intestine  is 
equipped.  Scattered  among  the  ordinary  reticular  cells  are  some 
which  undergo  constant  alterations  in  their  size  and  shape.  Origi- 
nally columnar  in  outline,  they  are  slowly  elongated,  because  their 
cytoplasm  gradually  increases  until  their  free  ends  project  beyond  the 
general  surface  of  the  mucosa.  The  internal  tension  having  reached 
its  physiological  limit,  their  inner  walls  rupture,  allowing  a  large  part 
of  their  contents  to  escape  into  the  intestinal  lumen.  Being  still  in 
possession  of  its  nucleus,  the  partially  emptied  cell  forms  new  material 
and  closes  the  defect  in  its  wall.  Many  of  these  cells,  however,  go 
to  pieces,  their  places  being  taken  by  cells  hitherto  dormant.  The 
material  which  is  in  this  way  extruded  into  the  intestinal  canal  con- 
tains large  amounts  of  mucin,  the  purpose  of  which  is  to  lubricate  the 
mucosa.  This  is  of  especial  value  in  the  large  intestine  in  which  the 
fecal  material  becomes  partially  hardened  on  account  of  an  absorption 
of  a  considerable  portion  of  its  water.  In  this  particular  segment  of 
the  alimentary  canal,  the  ordinary  goblet  cells  are  augmented  by  the 
modified  cells  of  the  crypts  of  Lieberkiihn.  It  will  be  pointed  out 
later  on  that  these  crypts  possess  a  true  secretory  power  only  in 
the  small  intestine  and  become  ordinary  mucous  glands  in  the  large 
intestine. 


CHAPTER  LXXVIII 

THE  DIGESTIVE  SECRETIONS 

A.  SALIVA 

The  Salivary  Glands. — Heidenhain  recognized  two  types  of  glands, 
namely,  the  mucous  and  the  albuminous  or  serous.  Strictly  speaking, 
this  classification  is  not  quite  correct,  because  even  the  simple  mucous 
glands  of  the  oral  mucosa  furnish  at  least  some  albuminous  material, 
while  traces  of  mucin  are  also  found  in  the  albuminous  salivary  glands. 
The  first  of  the  digestive  secretions  is  the  saliva.  It  is  supplied  by  the 
so-called  salivary  glands  of  which  there  are  six  in  all,  namely,  two 
parotid,  two  submaxillary  and  two  sublingual  glands.  Since  these 
organs  are  paired,  it  suffices  to  state  that  the  first  lies  above  the  ramus 
of  the  lower  maxillary  bone,  while  the  last  two  occupy  positions  upon 
the  floor  of  the  mouth  in  close  proximity  to  the  angle  of  the  jaw.  It  is 
true,  however,  that  the  arrangement  of  these  glands  differs  somewhat 
in  different  animals.  In  the  dog  and  cat,  for  example,  the  sublingual 
is  wanting  entirely,  its  function  being  transferred  to  the  so-called  retro- 
lingual  gland  which  is  situated  somewhat  nearer  the  angle  of  the  jaw. 
In  the  pig,  all  three  basal  glands  are  present,  i.e.,  the  submaxillary, 
retro-lingual  and  sublingual.  Traces  of  the  second  are  sometimes 
found  in  man,  in  addition  to  the  three  just  enumerated. 


THE    DIGESTIV^E    SECRETIONS  909 

Those  analomical  variations  aw  associated  with  very  striking 
histologieal  (Ufferences  as  well  as  with  tliffei-enees  in  the  character  of 
the  secretion.  Naturally,  the  saliva  obtained  from  the  mouth  is 
a  mixed  secretion,  because  it  is  derived  from  three  sources,  namely: 
(a)  from  Stenson's  duct  which  drains  the  parotid  gland  and  opens  upon 
the  inner  surface  of  the  cheek  opposite  the  se(^ond  molar  tooth,  (b) 
from  Wharton's  duct  which  conveys  the  submaxillary  secretion  into 
the  groove  next  to  the  frenulum  of  the  tongue,  and  (c)  from  the  ducts 
of  Rivinus  which  drain  the  sublingual  gland.  The  latter  are  multiple 
and  may  form  as  many  as  twenty  different  tubules.  In  the  dog,  one 
of  them  most  generally  attains  a  considerable  caliber  and  pursues  a 
course  parallel  to  Wharton's  duct.  It  is  known  as  the  duct  of  Bartho- 
lin. While  the  chemical  characteristics  of  saliva  will  be  dealt  with  in 
a  later  chapter,  it  may  be  stated  at  this  time  that  the  parotid  secretion 
is  clear  serous  in  character,  while  that  of  the  sublingual  gland  is  very 
viscous  and  stringy.  The  submaxillary  furnishes  a  secretion  which 
displays  intermediate  qualities. 

The  Histological  Character  of  the  Salivary  Glands.^ — Each  gland 
is  made  up  of  lobes  and  lobules,  and  each  lobule  in  turn  of  numerous 
groups  of  tubulo-saccular  alveoli  or  acini.  Each  acinus  consists  of 
a  number  of  large  and  rather  square  cells  which  surround  the  inner 
extremity  of  every  small  duct.  The  appearance  of  these  so-called 
chief  cells  varies  with  the  character  of  the  secretion.  In  the  fresh 
state,  those  forming  the  mucous  glands,  such  as  the  subhngual,  con- 
tain large  granules  of  mucinogen  which  is  the  precursor  of  mucin. 
In  the  fixed  state,  on  the  other  hand,  these  cells  appear  swollen,  the 
center  of  their  clear  cytoplasm  being  occupied  by  a  well  differentiated 
rounded  nucleus.  In  many  of  these  mucous  glands,  such  as  the  sub- 
maxillary of  the  dog  and  cat,  the  different  alveoli  of  chief  cells  are  in- 
vested by  crescentic  groups  of  marginal  cells  which  stain  deeply  and 
contain  no  mucinogen.  These  formations  are  the  demilune  cells  or 
crescents  of  Gianuzzi.  Other  glands  present  a  mixed  character  and 
embrace  acini  composed  of  mucous  cells  right  beside  those  made  up 
of  albuminous  cells.  This  is  true  not  only  of  the  submaxillary  gland 
of  man  in  which  the  serous  cells  predominate,  but  also  of  the  sublingual 
gland,  in  which  the  mucous  cells  are  more  numerous.  In  the  rabbit, 
the  submaxillary  presents  the  characteristics  of  a  se'rous  gland  and  the 
sublingual  those  of  a  mucous  gland.  It  need  scarcely  be  mentioned 
that  these  structural  peculiarities  are  associated  with  corresponding 
differences  in  the  character  of  the  saliva. 

Such  glands  as  the  parotid,  and  in  part  also  the  submaxillary, 
furnish  a  watery  and  non-viscid  secretion.  Their  chief  cells  are  filled 
with  small  granules  of  an  albuminous  type  which  constitute  the  mother- 
substance  of  the  active  principle  of  the  saliva,  called  ptyalin.  Upon 
it  depends  the  digestive  power  of  this  secretion.  Wliile  resting  in 
the  cells  these  granules  are  designated  as  zymogen  granules,  or  ptyalin- 
^  R.  Metzner,  in  Nagel's  Handb.  der  Physiol.,  Braunschweig,  1907. 


910 


THE    EXTERNAL    SECRETIONS 


ogen.     They  remain  inactive  until  discharged  into  the  ducts,  when 
they  are  immediately  converted  into  the  active  enzyme  ptyalin. 

Histological  Changes  During  Activity. — A  most  interesting  feature 
of  the  activity  of  glands  is  that  they  undergo  certain  very  characteris- 
tic changes  in  their  structure.  While  this  is  true  of  the  lacrimal, 
gastric  and  pancreatic  glands,  none  exhibit  them  in  a  more  striking 
manner  than  the  salivary  glands.  They  were  first  studied  by  Heiden- 
hain^  in  fixed  and  stained  preparations  of  the  parotid  and  submaxillary 
glands  of  the  rabbit,  but  have  also  been  observed  by  Langley^  and  others 
in  fresh  preparations.  When  resting  these  cells  are  large  and  faintly 
outlined  against  one  another  by  delicate  cell  walls.  Their  cytoplasm 
is  evenly  packed  with  granules  which  stain  deeply  with  the  ordinary 
dyes.  Near  the  basement  membrane  are  found  their  somewhat 
irrgular  and  dark  nuclei.  Contrary  to  this  picture,  a  cell  which  has 
been  made  to  secrete  for  a  considerable  length  of  time,  is  smaller,  more 


Fig.  490. — Acini  of  the  Submaxillary  Gland  During  Rest  (R)  and  Activity  (A). 
The  Dabk  Outer  Cells  Represent  the  Demilune  Cells. 


translucent,  and  contains  a  rounded  nucleus  which  occupies  a  position 
near  its  center.  Many  of  these  cells,  in  fact,  appear  merely  as  a  nar- 
row frame  of  cytoplasm,  investing  a  very  prominent  rounded  nucleus. 
The  granular  material  has  disappeared  from  the  entire  inner  part  of  the 
cell  and  is  now  arranged  in  the  form  of  a  narrow  zone  along  its  margin 
next  to  the  duct. 

These  changes  clearly  prove  that  these  cells  lose  a  certain  part  of 
their  substance  in"  the  course  of  their  activity;  in  fact,  Heidenhain 
states  that  many  of  them  disappear  altogether,  but  reform  their  con- 
tents during  the  subsequent  period  of  rest.  Of  special  interest  is 
the  fact  that  the  active  cell  gradually  discharges  its  zymogen  granules 
which,  as  has  been  mentioned  above,  give  rise  to  the  enzyme  ptyahn. 
Upon  the  cessation  of  this  stimulation,  the  stage  of  dissimilation  is 
followed  immediately  by  a  stage  of  assimilation  during  which  the 
material  lost  is  again  replenished.  A  clear  non-granular  material 
is  then  seen  to  invade  the  basal  segment  of  the  cell  which  is  gradually 

1  Noll,  Ergebn.  der  Physiol.,  iv,  1905. 

2  Jour,  of  Physiol.,  x,  1889,  433. 


THE    DIGESTIVE    SECRETIONS  911 

converted  into  the  granular  sul)stan(;o  so  clearly  betrayed  by  the  resting 
cell.  In  the  nmeous  cells  it  has  been  observed  that  their  large;  granules 
swell  up  antl  disappear,  probably  in  consequence  of  an  inhibition  of 
water  which  causes  the  mucinogen  to  be  converted  into  mucin.  The 
fact  that  salivary  secretion  is  associated  with  such  pronounced  histolog- 
ical changes  cannot  sur])rise  us,  if  it  is  renunnbered  that  the  submaxil- 
lary gland  of  the  tlog  seci-etes  its  own  weight  as  saliva  in  the  course;  of 
five  minutes  and  is  able  to  continue  this  process  for  many  hours. 

The  Paralytic  Secretion  of  Saliva. — It  has  been  found  by  CI. 
Bernard  (18(34)  that  the  division  of  the  chorda  tympani  innervating 
the  submaxillary  gland,  gives  rise  to  a  continuous  secnstion  of  saliva 
which  begins  about  two  days  after  the  division  and  persists  for  a  period 
of  about  two  or  three  weeks.  At  the  end  of  this  time  the  gland  is 
much  smaller  than  the  one  on  the  opposite  side  and  exhibits  a  charac- 
teristic picture  of  degeneration.^  The  cells  are  small  and  their  nuclei 
irregular,  fragmented  and  deeply  colored.  These  changes  may  be 
rendered  more  conspicuous  by  the  simultaneous  division  of  the  sympa- 
thetic fibers.  Obviously,  we  are  dealing  here  with  a  trophic  disturb- 
ance in  this  gland  which  finally  leads  to  itscxhaustion.  In  other  words, 
in  the  absence  of  its  normal  innervation,  the  local  nervous  elements 
are  quite  unable  to  effect  an  anabolism  sufficient  to  compensate  for 
the  catabolism  resulting  in  consequence  of  some  endogenous  stimulus. 
The  processes  of  dissimilation  finally  gain  the  upper  hand  and  cease 
only  after  the  secretory  material  has  been  completely  exhausted. 

The  Innervation  of  the  Salivary  Glands. — The  secretion  of  saliva 
is  a  reflex  act  made  possible  by  the  existence  of  definite  reflex  circuits. 
The  center  controlling  this  act  is  situated  in  the  medulla  oblongata, 
but  its  boundaries  have  not  been  established  with  any  degree  of  defi- 
niteness.  It  is  safe  to  assume,  however,  that  a  part  of  it  is  formed 
by  the  deep  origins  of  those  nerves  which  participate  in  the  innerva- 
tion of  the  salivary  glands,  namely  by  the  nuclei  of  the  facial  and 
glossopharyngeal  nerves.  Salivation  is  a  function  apportioned  to  the 
autonomic  system.  In  last  analysis,  therefore,  the  peripheral  nerves 
controlling  this  process  are  autonomic  in  their  character,  although 
they  select  typical  cerebrospinal  paths  in  gaining  access  to  the  center. 

On  the  efferent  or  motor  side,  the  salivary  center  is  connected  with 
the  different  glands  by  means  of  two  separate  sets  of  fibers,  constituting 
the  so-called  cerebral  and  sympathetic  paths.  The  former  reach  the 
glands  by  way  of  one  or  the  other  of  the  cranial  nerves,  while  the  latter 
first  enter  the  thoracic  sympathetic  system  and  then  ascend  in  the 
cervical  sympathetic  nerve.  Having  attained  the  superior  cervical 
ganglion,  they  follow  in  the  course  of  the  different  arteries  to  their 
respective  glands. 

This  arrangement  may  be  studied  most  conveniently  in  the  dog, 
in  which  animal  the  cerebral  nerve  supply  of  the  parotid  is  derived 

*  Maximow,  Archiv  fiir  mikr.  Anat.,  Iviii,  1901,  1,  and  Gerhardt  and  Burton- 
Opitz,  Pfluger's  Archiv,  xcvii,  1903,  317. 


912 


THE    EXTERNAL    SECRETIONS 


from  the  system  of  the  glossopharyngeal  nerve,  and  that  of  the  sub- 
maxillary from  the  system  of  the  facial  nerve.  In  the  first  instance, 
these  fibers  become  recognizable  in  the  tympanic  branch  of  the  glos- 
sopharyngeus  which  is  known  as  the  nerve  of  Jacobson.     From  here 


InfemrT^axil/an 
BrancAofdW- 


6anglxoru 

FiG.  491. — Schematic   Representation  of  the  Course  of  the  Cerebral  Fibers  to  the 

Parotid    Gland.     {Howell.) 

they  reach  the  otic  ganglion  by  way  of  the  small  superficial  petrosal 
nerve.  Upon  their  emergence  from  this  autonomic  outpost,  they 
attain  the  parotid  gland  by  following  the  highway  of  the  auriculo- 


TnferiofTnaxUlari/ 


.Branches 

Fig.  492. — Schematic  Representation  of  the  Course  of  the  Chorda  Titvipani  Ner\-e 
to  the  Subalaxillahy  Gland.     (Howell.) 


temporal  branch  of  the  inferior  maxillary  division  of  the  fifth  cranial 
nerve  (Fig.  491).  The  cerebral  fibers  of  the  submaxillary  gland  leave 
the  facial  system  in  the  form  of  a  small  nerve,  known  as  the  chorda 
tympani.     After  their  emergence  from  the  tympanic  cavity  through 


THE    DIGESTIVE    SECRETIONS  913 

the  Glaserian  fissure,  they  attach  themselves  to  the  lingual  branch  of 
the  fifth  cranial  nerve.  Having  followed  this  liiginvay  for  a  short 
distance,  the}-  again  pursue  a  separate  course  along  Wharton's  duct  to 
the  hilum  of  this  gland.  A  small  gangHon,  known  as  the  submaxillary 
ganglion,  marks  the  point  where  these  fibers  diverge  from  the  lingual 
nerve  (Fig.  402).  Langlev,  however,  believes  that  the  fibers  destined 
for  the  submaxillary  glanrl  do  not  form  synapses  here,  but  merely 
skirt  its  border,  while  those  fibers  which  innervate  the  sublingual 
gland  actually  terminate  in  this  structure  to  be  continued  as  secondary 
filx^rs.  This  ganglion,  therefore,  should  really  be  called  the  sublingual 
ganglion. 

Those  fibers,  which  first  enter  the  sympathetic  system,  traverse  the 
thoracic  ganglia  and  become  a  part  of  the  cervical  sympathetic  nerve. 
They  form  synapses  in  the  superior  cervical  ganglion,  whence  their 
postganglionic  fibers  continue  onward  along  the  arteries  supplying 
the  different  salivary  glands. 

On  the  afferent  or  sensory  side,  the  salivary  center  is  connected 
with  a  number  of  external  as  well  as  internal  receptors.  Under  or- 
dinary conditions,  however,  the  former  are  of  greater  value,  because  a 
flow  of  saliva  may  be  evoked  by  impressions  received  from  the  retina 
and  olfactory  cells  as  well  as  by  stimuH  produced  by  the  food  as  it 
traverses  the  oral  cavity.  Thus,  it  is  a  matter  of  common  exper- 
ience that  a  flow  of  saliva  may  be  ehcited  by  the  mere  smell  and  sight 
of  food  as  well  as  by  psychic  stimuli.  The  opposite  effect,  in  the  form 
of  a  dry  mouth  and  parched  throat,  is  incited  by  fear,  embarrassment 
and  anxiety.  Consequently,  the  salivary  center  must  be  connected 
reflexly  with  the  olfactory  cells,  the  retina  and  some  of  the  higher 
association  centers.  Lastly,  this  center  must  be  in  reflex  communica- 
tion with  various  general  interoceptors,  because  the  feeling  of  nausea, 
visceral  pain,  and  other  internal  sensations  frequently  give  rise  to  a 
copious  flow  of  saliva. 

The  Mechanism  of  Salivary  Secretion. — The  secretion  of  sahva 
is  a  reflex  act  which  may  be  evoked  by  the  stimulation  of  any  one  of  the 
receptors  just  mentioned.  It  should  not  be  assumed,  however,  that 
these  stimulations  affect  the  different  glands  in  a  perfectly  uniform 
manner,  giving  rise  to  a  definite  quality  of  saliva  under  all  circum- 
stances. The  truth  seems  to  be  that  the  quality  of  the  secretion  varies 
with  the  quahty  of  the  stimulation.  Thus,  a  more  specific  excitation 
of  the  parotid  jaelds  a  serous  saliva,  and  a  more  specific  stimulation 
of  the  subungual  a  mucous  saUva.  Such  variations  are  not  at  all 
uncommon,  and  their  occurrence  may  easily  be  demonstrated  experi- 
mentally. Thus,  if  a  fistulous  communication  is  estabhshed  between 
the  duct  of  the  submaxillar^'  gland  and  the  outside,  a  copious  flow  of 
sahva  may  be  produced  by  the  introduction  into  the  mouth  of  either 
a  0.25  per  cent,  solution  of  hydrochloric  acid  or  of  powdered  meat. 
On  analysis  it  will  then  be  found  that  the  type  of  sahva  secreted  after 
the  ingestion  of  meat,  contains  approximately  twice  as  much  sohd  ma- 
ss 


914  THE  EXTERNAL  SECRETIONS 

terial  as  that  obtained  with  the  aid  of  the  acid.  What  is  true  of  the 
submaxillary  must  also  be  true  of  the  other  glands;  but  naturally,  these 
differences  cannot  be  detected  so  readily-  directly  within  the  mouth, 
because  all  three  secretions  are  poured  into  this  common  reservoir  at 
one  time.  It  is  also  of  interest  to  note  that  the  daily  amount  of  saliva 
furnished  by  each  gland  exceeds  its  weight  ten  or  twelve  times.  The 
total  production  of  these  glands,  therefore,  cannot  be  less  than  one 
liter,  this  quantity  including  the  small  portion  which  is  poured  forth 
constantly  to  moisten  the  surfaces  of  the  mouth  as  well  as  those 
extra  amounts  which  are  produced  from  time  to  time  in  response  to 
stimulations. 

The  facts  which  maj'  be  mentioned  in  explanation  of  these  funda- 
mental differences  in  the  saliva,  must  necessarily  be  of  a  verj-  general 
kind,  because  they  are  based  upon  the  still  very  obscure  microphj-sical 
and  microchemical  occurrences  in  cells.  Thus,  it  may  be  assumed  that 
the  nerves  innervating  the  salivar}'  glands  are  capable  of  conveying 
impulses  of  different  kinds  or  that  each  nerve  contains  separate  sets 
of  fibers  which  react  specifically  to  different  stimuh.^  This  assump- 
tion finds  substantiation  in  the  fact  that  the  action  of  the  cerebral 
(parasympathetic)  nerve  is  quite  different  from  that  of  the  sympa- 
thetic nerve.  To  illustrate,  if  the  chorda  tj-mpani  is  stimulated,  it 
will  be  found  that  the  submaxillar}'  gland  reddens  and  becomes 
warmer  to  the  touch,  because  its  blood-vessels  are  markedly  dilated.- 
It  may  then  also  be  observed  that  the  blood  returned  from  this 
gland  possesses  a  much  brighter  color,  and  that  the  small  vein  draining 
it  pulsates  markedly.  These  pulsations  are  due  to  the  arterial  pulse 
which  is  propagated  at  this  time  directly  through  the  dilated  and 
non-resistant  capillaries.  Contrariwise,  the  excitation  of  the  cervical 
sympathetic  nerve  causes  this  gland  to  become  pale,  to  decrease  in 
volume,  and  to  become  distincth'  cooler  to  the  touch.  These  changes 
unmistakably  point  to  alterations  in  its  blood-supply,  the  exci  ation 
of  the  chorda  tympani  giving  rise  to  vaso-dilatation  and  the  stimula- 
tion of  the  sympathetic  fibers  to  vaso-constriction.^ 

Curiously  enough,  these  changes  in  the  vascularitj^  of  this  gland 
are  associated  with  verj^  decided  changes  in  the  c^uantity  and  quahty 
of  the  saliva.  •*  Very  soon  after  the  beginning  of  the  stimulation  of 
the  chorda  tympani,  Wharton's  duct  becomes  highly  distended  and 
discharges  a  quantity  of  saliva  four  or  five  times  larger  than  normal. 
The  secretion  itself  is  very  water}'  and  possesses  only  a  slight  \Tiscidity. 
It  contains  no  more  than  1  or  2  per  cent,  of  total  sohds.  If  a  suffi- 
ciently long  interval  is  allowed  to  separate  the  successive  stimulations, 

1  Pawlow,  Ergebn.  der  Physiol.,  iii,  1905. 

-  CI.  Bernard,  Compt.  rend.,  1858. 

^  These  differences  may  also  be  recognized  by  means  of  the  stromuhr  or  current 
measurer.     See:  Burton-Opitz,  Jour,  of  Phj'sioL,  xxx,  1903,  132. 

^  First  observed  by  Ludwig,  Arbeiten  aus  dem  physiol.  Institut  zu  Leipzig, 
1851. 


THE    DIGESTIVE    SECRETIONS  915 

this  experiment  may  1m'  rcjx'iiled  foi  in;iiiy  hours  without  any  apparent 
decrease  in  the  intensity  of  the  reaction.  Conlniry  to  this  result,  the 
excitation  of  the  cervical  synii)athetic  nerve  j'ields  only  a,  few  drops  of 
saliva  which  is  characterized  by  its  turl)idity  and  richness  in  total 
solids  (G  per  cent.).  On  the  one  hand,  therefore,  wo  obtain  a  vaso- 
dilatation and  copious  flow  of  a  very  watery  saliva  and,  on  the  other, 
a  vaso-constriction  and  a  scanty  flow  of  a  very  viscous  saliva.  Very 
similar  changes  may  be  evoked  in  the  parotid  gland;  in  this  case, 
however,  the  excitation  of  the  sympathetic  nerve  does  not  yield  an 
appreciable  quantity  of  secretion,  although  it  produces  marked  his- 
tological changes  in  the  secretory  cells. 

Regarding  the  intracellular  changes  little  can  be  said  unless  we 
confine  this  discussion  to  the  structural  alterations  during  rest  and 
activity.  Secretion  is  essentially  a  transudation  of  water  from  the 
blood-vessels  into  the  excretory  ducts,  controlled,  of  course,  by  the 
constituents  of  the  cell.  It  is  conceivable  that  the  agents  most 
actively  concerned  in  this  process  are  those  granules  of  the  cWoplasm 
which  take  up  water,  swell  and  discharge  their  contents  into  the  ducts. 
How  this  osmotic  play  may  be  influenced  by  impulses  brought  to 
these  cells  by  way  of  the  secretory  fibers,  is  largely  a  matter  of  specula- 
tion into  which  we  cannot  enter  at  this  time.  It  is  certain,  however, 
that  the  cell  is  not  merely  a  pumping  mechanism  for  the  flow  of  water, 
but  also  serves  as  a  generator  of  organic  material  which  is  later  on 
transferred  into  the  watery  medium.^  Obviously,  the  waves  of  excita- 
tion derived  from  the  chorda  t\anpani,  must  increase  this  transudation 
as  well  as  rupture  the  granules,  but  it  is  also  conceivable  that  the 
aforesaid  secretory  nerves  may  innervate  different  elements  of  the 
gland.  While  it  has  been  showm  that  they  terminate  around  the  vari- 
ous alveoli,  forming  here  delicate  arborizations  below  the  basement 
membrane,  certain  evidence  has  also  been  presented  to  prove  that  the 
cerebral  autonomic  fibers  are  apportioned  to  the  chief  cells  and  the 
sympathetic  fibers  to  the  cells  of  the  crescents  of  Gianuzzi.  At  least, 
this  arrangement  seems  to  prevail  in  the  submaxillar}'  gland  of  the  dog. 
Upon  the  basis  of  Mliller's  Law  of  the  specific  nerve  energy  we  might 
then  assume  that  these  mechanisms  react  differently  to  different  kinds 
of  stimulations  enacted  by  the  food.  In  one  case,  we  would  obtain  a 
typical  chorda-saHva,  and  in  another,  a  typical  sympathetic-saliva, 
or  even  a  mixture  of  the  two. 

Barcroft  and  Piper^  have  sought  to  obtain  a  measure  of  the  energy 
evolved  by  a  secreting  gland  bj^  ascertaining  its  respiratory  exchange 
when  resting  and  when  active.  Thus,  it  has  been  found  that  the  sub- 
maxillary gland  of  the  dog  consumes  0.25  c.c.  of  oxygen  in  a  minute  and 
liberates  0.17  c.c.  of  carbon  dioxid.  During  this  time  6  grams  of 
gland-tissue  furnish  about  1.1  calorie  of  heat.     The  active  organ,  on 

1  MacuUum  introduces  the  factor  of  differences  in  surface-tension,  Ergebn.  der 
Physiol.,  xi,  1911. 

2  Jour,  of  Physiol.,  xliv,  1912,  359. 


916  THE    EXTERNAL    SECRETIONS 

the  Other  hand,  i-cquires  0.86  c.c.  of  ox^-gen  per  minute  and  ^nelds 
6.39  c.c.  of  carbon  dioxid. 

It  has  also  been  noted  that  the  activity  of  the  sahvary  glands  is  ac- 
companied by  changes  in  their  electrical  potential  which  originate  in  the 
formation  of  electrolytes  and  their  movements  through  animal  mem- 
branes. These  differences  are  similar  to  those  observed  in  active 
muscle  and  nerve,  and  may  be  detected  by  applying  the  poles  of  a  gal- 
vanometer to  the  surface  and  the  hilum  of  the  gland.  The  surface  is 
then  galvanometrically  positive.  In  the  case  of  the  submaxillary 
gland,  the  stimulation  of  the  chorda  tympani  first  increases  and  then 
decreases  this  positivity,  which  fact  signifies  that  this  current  pos- 
sesses a  diphasic  character.  The  one  evoked  by  the  stimulation  of  the 
sympathetic  nerve,  on  the  other  hand,  presents  itself  merely  as  a 
negative  variation  of  the  current  of  rest. 

The  Action  of  Drugs  upon  the  Secretion  of  Saliva. — If  atropin  is 
administered  intravenously  or  is  injected  into  the  duct  of  the  sub- 
maxillary gland,  the  stimulation  of  the  chorda  tympani  soon  ceases  to 
produce  its  characteristic  secretory  effect.  Meanwhile,  however,  the 
excitation  of  the  sympathetic  nerve  remains  effective  and  much  larger 
doses  of  this  alkaloid  are  required  to  abolish  the  flow  of  this  type  of 
saHva.  The  vaso-dilator  action  of  the  chorda  also  persists  until 
additional  doses  have  been  administered.  This  peculiar  result  sug- 
gests that  atropin  paralyzes  the  endings  of  the  cerebral  autonomic 
fibers,  but  does  not  affect  the  secreting  cells  themselves.  Secondly, 
it  points  toward  a  definite  chemical  difference  between  the  nervous 
elements  constituting  the  cerebral  or  parasj-mpathetic  system  and 
those  forming  the  sympathetic  system  proper.  Pilocarpin  evokes 
a  copious  flow  of  saHva  which  is  accompanied  by  vaso-dilatation. 
This  agent,  therefore,  possesses  an  antagonistic  action  to  the  preceding 
one  and  stimulates  the  endings  of  the  cerebral  nerve.  Ergotoxin  para- 
lyzes the  sympathetic  mechanism,  but  does  not  affect  the  one 
controlled  by  the  chorda  tympani.  This  fact,  again,  speaks  for  the 
previous  contention  that  the  cerebral  and  sympathetic  autonomic  fibers 
differ  from  one  another  in  their  chemical  constitution.  Adrenalin 
evokes  a  constriction  of  the  blood-vessels  which,  in  some  animals,  is 
soon  followed  by  a  vaso-dilatation  and  a  considerable  flow  of  saliva. 

Nicotin  may  be  used  to  abolish  the  action  of  the  secretory  nerves, 
but  since  it  does  not  affect  the  secreting  cells  nor  the  nerve  terminals, 
it  must  produce  this  effect  in  an  indirect  way.  It  is  a  well-known 
fact  that  it  destroys  the  synapses  and  hence,  may  be  employed  to  cause 
a  functional  discontinuity  between  the  preganglionic  and  postgan- 
glionic paths.  Thus,  if  the  submaxillary  (sublingual)  ganglion  is 
moistened  with  a  solution  of  this  alkaloid,  the  stimulation  of  the  chorda 
tympani  centrally"  to  this  ganglion  ceases  to  evoke  a  secretion  from  the 
sublingual  gland,  because  the  fibers  destined  for  this  organ  are  relayed 
at  this  point. ^  Moreover,  inasmuch  as  this  procedure  does  not  block 
^  Langley,  Proc.  R.  Soc.  London,  1S89. 


THE    DIGESTIVE    SECRETIONS  917 

the  impulses  apportioned  to  the  submaxillary  ^liind  it  may  rightly  be 
concluded  that  the  fibers  innervatinjz;  this  organ  pa^s  directly  through 
the  aforesaid  ganglion  without  forming  new  connections. 

Facts  Disproving  the  Filtration  Theory. — While  U  cannot  be  denied 
that  filtration  plays  an  important  jjart  in  the  secretion  of  saliva,  we  are 
not  warranted  in  believing  that  it  is  the  only  factor  mediating  this 
process.  It  has  previously  been  noted  that  the  excitation  of  the  chorda 
tympani  gives  rise  to  a  vaso-dilatation  and  a  copious  flow  of  a  very 
watery  tj-pe  of  saliva,  while  the  stimulation  of  tiie  cervical  sympathetic 
nerve  evokes  a  vaso-constriction  and  a  scanty  flow  of  a  very  viscous 
saliva.  While  these  changes  may  at  first  be  thought  to  favor  filtration, 
they  cannot  bo  interpreted  in  this  way  if  contrasted  with  such  facts 
as  the  following: 

(a)  We  have  noted  above  that  the  formation  of  saliva  is  not  wholly 
dependent  upon  the  blood-supply,  but  is  more  closely  related  to  the 
influences  of  the  nervous  system. 

(6)  It  has  also  been  pointed  out  that  this  secretion  may  be  either 
increased  or  decreased  by  drugs  without  altering  the  pressure  existing 
in  the    capillaries  of  the  gland  from  which  the  material  is  taken.  ^ 

(c)  Inasmuch  as  the  saliva  contains  bodies,  such  as  mucin  and  ptya- 
lin,  which  are  not  present  in  the  body-fluids,  the  secreting  cells  must 
possess  the  specific  power  of  forming  them.  Carlson  states  that  saliva 
also  contains  a  diastase  which  is  present  here  in  smaller  amounts  than 
in  the  blood. 

(d)  It  has  been  shown  that  saliva  may  also  be  secreted  by  the  sub- 
maxillary glands  after  its  artery  has  been  ligated,  and  that 

(e)  The  normal  gland  may  be  made  to  secrete  against  a  higher  pres- 
sure than  the  capillary  pressure. 

Under  ordinary  conditions,  the  sahvary  cells  derive  their  secre- 
tory material  from  the  blood-capillaries  in  which  the  pressure  does  not 
rise  above  40  to  60  mm.  Hg.  They  then  discharge  it  into  the  salivary 
duct  in  which  the  pressure  approximates  zero.  This  arrangement 
favors  filtration.  It  can  be  shown,  however,  that  these  cells  are  also 
able  to  secrete  against  a  pressure  which  not  only  exceeds  the  capillary 
pressure,  but  also  that  prevailing  in  the  carotid  artery.  Thus,  if 
Wharton's  duct  is  connected  with  a  mercury  manometer,  and  the 
chorda  tympani  is  stimulated  repeatedly  at  intervals,  it  will  be  found 
that  the  mercury  continues  to  rise  until  it  eventually  indicates  a  pres- 
sure at  least  twice  as  high  as  that  existing  in  the  capillaries  of  the  sub- 
maxillary gland.  In  fact,  Hill  and  Flack^  have  succeeded  in  obtaining  a 
salivary  pressure  of  240  mm.  Hg  against  a  blood-pressure  of  1 30  mm.  Hg. 
Now%  if  filtration  were  the  only  factor  concerned  in  the  formation  of 
saliva,  a  relationship  of  this  kind  could  not  be  successfully  established. 
The  same  conclusion  may  be  derived  from  the  fact  that  even  the 

1  Sarmus,  Zeitschr.  fiir  Biologie,  Iviii,  1912,  185. 

2  Proc.  R.  Soc.  London,  Ixxxv,  1912. 


918  THE  EXTERNAL  SECRETIONS 

bloodless  gland  is  able  to  secrete  saliva,  but  since  this  organ  is  unaWc 
to  acquire  new  material,  the  secretion  will  be  scanty  in  amount. 

The  General  Character  of  Saliva. — When  collected  directly  from 
the  mouth,  saliva  is  a  transparent,  slightly  opalescent  and  shmy 
liquid,  possessing  a  moderate  viscosity  and  a  specific  gravity  of  1.002 
to  1.006.^  On  stanchng  it  becomes  cloudy,  this  change  being  due  to  the 
deposition  of  calcium  carbonate  in  consequence  of  the  escape  of  car- 
bonic acid  which  formerly  retained  this  salt  in  the  form  of  its  bicarbon- 
ate. The  reaction  of  saliva  is  sUghtly  alkaline,  but  may  become 
moderately  sour  during  the  night  and  during  fevers  and  digestive 
disorders.  The  reason  for  this  is  the  diminution  in  its  quantity 
which  favors  the  bacterial  decomposition  of  its  organic  constituents. 
Its  active  principle,  ptyalin,  ceases  to  act  in  a  markedly  alkaline  or 
shghth^  acid  medium;  in  fact,  free  hydrochloric  acid  in  an  amount 
equalling  a  0.003  per  cent,  solution  suffices  to  stop  its  action  entirely. 
Temperatures  of  0°  C.  and  65°  to  70°  C.  have  a  similar  effect. 

The  quantity  of  saliva  secreted  in  a  day  has  been  estimated  in  man  at  1  to  2 
liters,  in  horses  at  40  liters,  and  in  the  large  ruminating  animals  at  60  liters.  It 
contains  0.5  per  cent,  of  solids,  which  may  be  classified  as  follows: 

Organic :  Mucin,  which  gives  to  it  its  ropy,  mucilaginous  character. 
Ptyalin,  an  amylolytic  enzyme. 
Protein,  of  the  nature  of  a  globulin. 
Potassium  sulphocyanide. 
Inorganic:  Sodium  chlorid,  sodium  carbonate. 

Calcium  phosphate  and  carbonate,  magnesium  phosphate  and  potas- 
sium chlorid. 

Suspended  in  the  saUva  are  desquamated  epithelial  cells,  disintegrating  leukocytes, 
the  so-called  "salivary  corpuscles."  gland  cells  and  clumps  of  mucin.  Among  the 
living  organisms  might  be  mentioned  a  number  of  saprophytes,  such  as  leptothrix 
buccalis,  and  pathogenic  bacteria. 


CHAPTER  LXXIX 

THE  DIGESTIVE  SECRETIONS  (CONTINUED) 

B.  THE  GASTRIC  AND  PANCREATIC  SECRETIONS 

The  Gastric  Glands. — The  cavity  of  the  stomach  is  divided  into 
a  cardiac,  fundic  and  pyloric  portion.  It  is  fined  throughout  by  a  soft 
and  thick  mucosa  which  presents  a  honeycomb  appearance  owing  to 
the  presence  of  numerous  shallow  polygonal  depressions.  Its  unusual 
thickness  is  due  veiy  largely  to  the  fact  that  it  is  made  up  of  an  almost 
infinite  number  of  closely  packed,  long  tubular  glands  which  are  held 

1  Burton-Opitz,  Biochem.  Bull.,  1919;  Xeilson  and  Terry,  Am.  Jour,  of  Physiol., 
XV,  1906,  406;  Tezas,  Maly,  xxv,  1905. 


THE    DIGESTIVE    SECRETIONS 


919 


together  by  slight  amounts  of  reticular  tissue.  In  between  these 
glands  are  found  columnar  goblet  cells  which  secrete  mucus.  The 
former  consist  of  a  basement  membrane  which  is  covered  externally 
with  epith(>liuni.  Toward  the  gastric  surface;  the  enlarged  outer 
portions  of  tlu^sc  tubuh^s  narrow  into  a  duct  which  is  lined  by  short 

columnar  cells.  In  many  cases  the  latter 
5^ttfiyl  ai'c  mucus-secreting,  the  same  as  those 
situated  directly  upon  the  innei-  surface  of 
tlie  mu(!Osa.  The  epithelium  of  the  outer 
jwrtions  of  these  tubules  differs  somewhat 


Fig.  493.  Fiu. 

Fig.  493. — Diagrammatic  Representation  of 


494. 

\.  FuNDic  Gland. 


C,  Chief  cells;  P,  parietal  cells;  D,  duct  of  gland;  N,-  neck  of  gland. 

Fig.  494. — Part  of  Tubule  of  a  Fundus  Gland,  with  the  Lumen  and  Secretory 
Canaliculi  Stained  Black;  the  Gland-cells  are  al.so  Shown. 

C,  Chief  or  central  cells;  p,  parietal  or  oxyntic  cells;  Z,  lumen  of  tubule  prolonged 
into  arborescent  canaliculi  which  penetrate  to  the  parietal  cells.     {Zimmermann.) 

in  different  parts  of  the  stomach,  so  that  we  are  able  to  recognize 
three  distinct  types  of  gastric  glands,  namely: 

(a)  The  glands  of  the  cardiac  end,  which  are  simple  tubular  or  tubulo-racemose 
in  character  and  are  lined  by  short  columnar  cells  containing  much  granular  mate- 
rial. They  are  few  in  number  and  are  found  principally  in  the  immediate  vicinitj^ 
of  the  esophageal-gastric  junction. 

(6)  The  glands  of  thefundtis,  which  are  distributed  throughout  the  remaining 
portion  of  the  cardia  and  the  entire  fundus.  They  consist  as  a  rule  of  three 
or  four  long  tubular  glands  which  unite  into  a  short  duct.  The  low  columnar 
cells  lining  these  ducts  gradually  pass  over  into  the  true  secretory'  cells  which  are 
somewhat  polyhedral  in  shape  and  are  partly  filled  with  granules  occupying  a  posi- 


920  THE    EXTERNAL    SECRETIONS 

tion  next  to  the  lumen  of  the  duct.  These  cells  line  the  entire  secretory  portion  of 
these  glands  and  are  known  as  central  or  chief  cells.  Wedged  in  between  these 
and  the  basement  membrane  are  a  number  of  isolated  cells  which  present  a 
spheroidal  or  ovoid  shape,  and  are  connected  with  the  main  duct  by  a  network 
of  minute  channels  situated  in  between  the  chief  cells.  Nearer  the  duct,  these  cells 
are  more  abundant  and  occupy  a  position  in  between  the  chief  cells  and  close  to 
the  lumen  (Bensley).  These  cells  are  known  as  the  parietal  or  oxynlic  (acid)  cells. 
(c)  The  glands  of  the  pyloric  end,  which  are  scattered  throughout  the  pyloric 
canal,  are  much  longer  than  those  of  the  fundus  and  are  made  up  wholly  of  chief 
cells.  The  latter  boar  a  close  resemblance  to  those  composing  the  fundic  glands, 
but  are  not  quite  so  granular.  Directly  at  the  pylorus  they  increase  in  size,  and 
become  more  convoluted  and  more  deeply  seated.  They  are  thus  gradually 
transformed  into  the  glands  of  Brunner  of  the  submucous  layer  of  the  duodenum. 

Histological  Changes  in  the  Gastric  Glands  on  Secretion. — Accord- 
ing to  Heidenhain,  the  chief  cells  of  the  inactive  glands  are  large  and 
clear,  save  for  a  certain  amount  of  granular  material  which  is  collected 
very  largely  near  the  duct.  During  secretion,  these  granules  are  dis- 
charged into  the  duct,  leaving  the  outer  zones  of  the  cells  perfectly 
clear.  ^  The  parietal  cells  undergo  a  similar  diminution  in  their  size, 
but  do  not  exhibit  so  distinct  a  clearing  of  their  cytoplasm.  Thus,  we 
are  again  confronted  by  the  fact  that  these  cells  do  not  merely  form  a 
pumping  mechanism  for  water,  but  actively  concentrate  the  original 
liquid  by  preformed  material. 

The  Origin  of  the  Active  Principles  of  Gastric  Juice. — Heidenhain ^ 
conceived  the  idea  of  isolating  a  certain  portion  of  the  stomach  and 
giving  it  an  artificial  fistulous  opening  to  the  outside  through  which 
gastric  juice  could  be  obtained  separately  from  its  different  segments. 
This  operative  procedure  has  been  improved  upon  by  Pawlow^  in 
such  a  way  that  these  gastric  pockets  need  not  be  deprived  of  their 
normal  blood  and  nerve  supply.  Upon  analysis  of  these  different 
samples  of  gastric  juice  it  was  found  that  the  secretion  from  the  pyloric 
end  is  free  from  hydrochloric  acid,  but  not  from  pepsin,  while  that 
from  a  cul-de-sac  of  the  fundus  is  strongly  acid  in  reaction  and  contains 
much  pepsin.  Inasmuch  as  the  pyloric  glands  are  made  up  of  chief 
cells,  while  the  fundic  glands  also  embrace  border  cells,  it  was  then 
concluded  that  the  pepsin  is  furnished  by  the  chief  cells,  and  the 
hydrochloric  acid  by  the  parietal  cells. 

In  support  of  this  hypothesis  it  has  been  shown  that  the  esophagus 
of  the  frog  is  beset  with  glands  which  are  made  up  of  chief  cells  and 
secrete  only  pepsin,  while  the  glands  of  the  fundus  of  the  stomach  are 
composed  of  ovoidal  cells  which  produce  large  quantities  of  acid  but 
little  pepsin.  Further  light  is  thrown  upon  this  topic  by  the  fact 
that  the  secretion  taken  from  the  pyloric  cul-de-sac,  does  not  digest 
protein  material  nor  curdle  milk  unless  it  is  acidified  by  the  addition  of 
dilute  hydrochloric  acid.  Thus,  while  these  glands  secrete  pepsin, 
this  agent  remains  impotent  as  long  as  it  is  permitted  to  remain  in  an 

1  Langley,  Jour,  of  Physiol,  iii,  1880,  269. 

2  Hermann's  Handl).  der  Physiol.,  1883. 

3  Die  Arbeit  der  Verdauungsdriisen,  Wiesbaden,  1898. 


THE    DIGESTIVE    SECRETIONS  921 

alkaline  medium.  Curiously  enousH,  therefore,  w(^  are  confronted  here 
by  the  peculiar  functional  arran{j;(Mnent  that  the  alkaline^  i)roduct  of  the 
chief  cells  is  acidified  almost  immediately  by  the  secn^tion  of  the  parietal 
cells,  and  that  the  alkaline  juice  of  the  pyloric  pai't  of  Ihe  stomach 
must  first  be  mixed  with  the  fundic  acid  l)efore  it  can  exert  its  charac- 
teristic action. 

The  genesis  of  hydrochloric  acid  has  also  received  attention  from 
the  chemists.  Thus,  it  has  been  suggested  that  it  is  derivcid  fiom  the 
chlorids  of  the  blood,  but  the  natun^  of  this  decomposition  is  not  known. 
The  contrary  view  is  that  it  orginates  from  the  sodium  chlorid  of  the 
food  upon  the  surface  of  the  gastric  mucosa.  The  latter  view,  however, 
could  be  criticized  upon  the  ground  that  a  copious  secretion  of  gastric 
juice  containing  an  abundant  quantity  of  hydrochloric  acid,  may  also 
be  evoked  without  the  introduction  of  food  into  the  stomach ;  for  ex- 
ample, by  the  process  of  sham-feeding,  or  by  allowing  an  animal  to  see 
or  to  smell  food.  More  recently,  the  preceding  hypothesis  pertaining 
to  the  origin  of  the  hydrochloric  acid  in  the  parietal  cells  has  received 
additional  support  in  the  results  of  the  microchemical  tests  of  Fitz- 
gerald^ and  Hammett.2  On  injecting  a  ferrocyanid  and  a  ferric 
salt  into  the  circulation  of  animals,  a  deposition  of  Prussian  blue  was 
noted  not  only  in  the  lumina  of  the  gastric  glands  bu :  also  in  the  cannal- 
iculi  of  the  parietal  cells  and  even  within  the  cytoplasm  of  the  latter. 
Since  this  characteristic  precipitate  was  not  found  in  the  chief  cells 
and  results  only  in  the  presence  of  free  acid,  it  was  concluded  that  the 
hydrochloric  acid  orginates  in  the  border  cells,  Harvey  and  Bensley^ 
are  at  issue  with  this  view,  because  they  state  that  the  parietal  cells  are 
alkaline  in  their  reaction  and  believe  that  a  deposition  of  this  coloring 
material  takes  place  only  upon  the  mucosa  of  the  stomach  and  in  the 
orifices  of  the  ducts  of  the  different  glands.  Without  entering  in 
detail  into  the  technique  of  the  microchemical  tests  of  Hammett,  it 
may  be  stated  that  these  later  experiments  fully  confirm  the  conten- 
tion of  Heidenhain  that  the  parietal  cells  secrete  the  hydrochloric  acid. 

The  gastric  glands,  therefore,  present  the  same  functional  picture 
as  the  salivary  glands.  They  are  not  merely  passive  filters  but  living 
laboratories  in  which  the  contents  of  the  blood  and  lymph  are  drawm 
upon  to  yield  new  and  very  characteristic  vital  products.  This  can 
easily  be  proven  by  comparing  the  composition  of  the  gastric  secre- 
tion with  that  of  the  body-fluids.  Thus,  we  obtain  in  the  former  such 
characteristic  bodies  as  mucin,  pepsin,  hydrochloric  acid,  and  rennin. 

Methods  Employed  to  Obtain  Gastric  Juice. — The  experiments  of 
the  older  observers  (Spallanzani,  1729-1799)  were  carried  out  with 
various  foods  which  were  sewed  in  linen  bags  or  enclosed  in  perforated 
capsules  of  wood.  Clean  sponges  attached  to  strings  have  also  been 
used,  the  sponges  being  removed  later  on  and  their  contents  squeezed 

'  Proc.  R.  Soc,  London,  1910. 

2  Anat.  Record,  ix,  1915,  21. 

3  Biolog.  Bull.,  xxiii,  1912,  225. 


922  THE    EXTERNAL    SECRETIONS 

out.  These  procedures  have  been  displaced  in  more  recent  years  by 
the  method  of  aspirating  or  siphoning  the  gastric  juice  by  means  of  a 
long  tube  of  rubber  inserted  through  the  esophagus.  A  number  of 
cases  have  also  been  reported  in  recent  years  of  persons  in  whom  it 
became  necessary  to  establish  a  free  communication  between  the 
gastric  cavity  and  the  outside.  The  first  of  these  has  been  recorded  by 
the  American  frontier  physician  Beaumont,^  the  subject  beir^  the 
Canadian  hunter  Alexis  St.  Martin,  whose  abdominal  and  gastric  walls 
had  been  extensively  lacerated  by  the  premature  discharge  of  a  gun, 
so  that  even  the  lung  protruded  from  the  wound.  In  healing,  a  fis- 
tulous communication  was  formed  between  the  outside  and  the  cavity 
of  the  stomach,  but  the  escape  of  the  gastric  contents  was  prevented  by 
a  flap  of  mucous  membrane  which  acted  as  a  valve  and  did  not  allow 
of  an  unobstructed  view  of  the  interior  of  this  organ.  Beaumont 
determined  the  time  it  took  to  digest  meals  and  found  that  pork  re- 
quired a  longer  period  for  its  digestion  than  beef.  He  also  noted  the 
character  of  the  gastric  mucosa  in  health  and  disease,  and  obtained 
sufficient  quantities  of  pure  gastric  juice  for  analysis.  The  results  of 
these  studies  are  accepted  even  to-day  as  wholly  accurate.  Further- 
more, he  introduced  various  foods  through  this  fistulous  opening  and 
withdrew  them  again  later  on  to  see  what  changes  had  taken  place  in 
them. 

Since  the  time  of  Beaumont  gastric  fistulas  have  been  established 
in  a  number  of  persons  suffering  from  occlusion  of  the  esophagus  in 
consequence  of  erosion  by  corrosive  alkali.  Cases  of  this  kind  have 
been  reported  by  Richet,  Sommerfeld  and  Roder,-  Bickel,^  Umber, ^ 
Kaznelson,^  and  Carlson.^  The  subject  of  the  most  recent  report 
was  operated  upon  16  years  ago  and  has  since  led  a  normal  life, 
offering  himself  repeatedly  for  physiological  observation.  This  same 
condition  may  be  produced  in  animals  by  operative  means,  the  fis- 
tulous opening  in  the  abdominal  wall  being  permanently  closed  by  a 
silver  cannula.  The  outside  cover  of  the  latter  is  made  so  that  it 
can  be  removed  at  any  time  for  the  purpose  of  procuring  gastric 
juice.  In  this  catagory  also  belong  the  procedures  of  Heidenhain 
and  Pawlow  which  permit  of  the  resection  and  isolation  of  a  particular 
portion  of  the  stomach  and  the  separate  study  of  its  secretion. 

Artificial  gastric  juice  may  be  prepared  by  extracting  macerated 
gastric  mucosa  with  dilute  hydrochloric  acid.  This  liquid  is  filtered 
and  warmed  to  the  temperature  of  the  body  whenever  required  for  use. 
For  coagulated  albumin  it  should  have  a  strength  of  0.16  per  cent. 
Pepsin  may  be  obtained  by  placing  the  washed  mucosa  in  alcohol 

1  The  Physiology  of  Digestion,  1833. 

2  Archiv  fur  Physiol.,  1905. 

2  Deutsch.  med.  Wochenschr.,  1906. 
*  Berliner  klin  Wochenschr.,  1905. 
^  Pfliiger's  Archiv,  xcviii,  1907,  327. 
^  Am.  Jour,  of  Pliysiol.,  xxxi,  1912,  151. 


THE    DIGESTIVE    SECRETIONS  923 

for  24  hours,  drying  it,  pulverizing  it  and  extracting  it  in  glycerin  for 
()  or  7  (lays.  On  addition  of  alcohol  to  th(!  filtrat(\  tlu;  pepsin  is 
preci[)itati'd,  which  may  then  be  added  to  dilute  hydrochloric  acid. 
The  Characteristics  of  Gastric  Juice. — When  obtained  from  a 
fasting  animal,  gastric  juice  is  (juite  clear,  odorless,  acid  in  reaction, 
and  sour  to  the  taste.  Its  specific  gravity  varies  between  1.002  and 
1.006  and  its  depression  of  the  freezing  point  between  0.47°  and 
0.65°  C.^  Its  quantity  may  be  considerable,  large  dogs  yielding 
as  much  as  1  liter  in  the  course  of  3  hours.  Human  subjects  secrete 
700  c.c.  during  a  moderate  meal  and  an  average  total  per  day  of  1500 
e.e.  As  Carlson-  has  pointed  out,  the  gastric  glands  of  a  healthy 
person  are  never  wholly  dormant,  but  secrete  continuously  in  amounts 
varying  b(>tween  2  and  50  c.c.  in  an  hour;  the  higher  figures,  however, 
are  exceptional.  Gastric  juice  contains  only  0.3  to  0.6  per  cent,  of 
total  solids,  as  follows: 

Acid 0 .  46-0 .  58  per  cent. 

Chlorin 0.49-0.62  per  cent. 

Total  solids 0.43-0.60  per  cent. 

Ash 0.06-0. 16  per  cent. 

If  gastric  juice  is  cooled  and  is  allowed  to  stand,  it  becomes  cloudy  and  gives  rise 
to  a  deposit  of  finely  granular  and  highly  refracting  material  which  appears  to 
consist  of  the  active  principle  pepsin.  This  agent  unfolds  its  action  only  in  an  acid 
medium  which  is  supplied  to  it  by  the  hydrochloric  acid  (Prout,  1824).  Since  the 
latter  is  present  in  amounts  varying,  in  dogs,  between  0.45  and  0.58  per  cent,  and, 
in  man,  between  0.25  and  0.35  per  cent.,  about  3  grams  of  hydrochloric  acid 
must  be  produced  at  each  meal.  In  some  persons,  however,  there  maj'  be  an 
achlorhydria  or  absence  of  hydrochloric  acid,  although  some  peptic  digestion  may 
still  be  present.  A  condition  of  this  kind  constitutes  a  diagnostic  sign  of  consider- 
able value.  It  commonly  develops  in  the  course  of  carcinoma  of  the  stomach. 
The  reverse  condition  is  hyperchlorhydria,  which  is  usually  associated  with  a 
hyperpeptic  activity  and  a  deficiency  in  mucus.  The  cause  of  this  excess  in  acid 
usually  lies  in  a  hj'perirritability  of  the  nervous  system,  as  well  as  in  lesions  produc- 
ing a  constant  stimulation  of  the  gastric  mucosa,  such  as  ulcers  and  growths  else- 
where in  the  abdominal  cavity. 

The  acidity  of  the  gastric  juice  is  usually  ascertained  by  means  of  a  test  break- 
fast. \Mien  only  a  light  evening  meal  is  taken,  the  stomach  should  be  empty 
in  the  morning,  i.e.,  after  a  period  of  rest  of  about  12  hours.  The  breakfast  should 
consist  of  a  roll  or  five  crackers  or  bi.scuits  and  a  cup  of  weak  tea.  A  sample  of 
gastric  juice  is  obtained  45  minutes  later  by  means  of  the  stomach  tube.  While 
the  analytical  procedures  to  be  followed  in  this  case  cannot  be  described  in  detail 
in  a  book  of  this  kind,  it  might  be  mentioned  that  the  unfiltered  juice  may  be  ti- 
trated with  X/10  NaOH.  using  phenolphthalein  as  an  indicator.  Although  the 
determination  of  the  free  hydrochloric  acid  may  be  made  with  Glinzberg's  or  Toper's 
reagent,^  the  most  accurate  procedure  is  to  ascertain  the  number  of  hydrogen  ions 
in  the  juice  in  accordance  with  the  gas-chain  method.'*     The  former  reagent  con- 

1  Rosemann,  Pfliiger's  Archiv,  cxviii,  1907.  467,  and  Sommerfeld,  Archiv  fur 
Physiol,  1905,  455. 

2  Am.  Jour,  of  Physiol.,  xxxvii,  1915,  50. 

3  Zeitschr.  fur  physiol.  Chemie,  xix,  1894,  104;  also:  Christiansen,  Bioch. 
Zeitschr.,  xlvi,  1912,  24. 

*  Panton  and  Tidy,  Analysis  of  Gastric  Contents,  Quart.  Jour,  of  Medicine,  iv, 
1910-1911. 


924  THE    EXTERNAL    SECRETIONS 

sists  of  a  mixture  of  phloroglucin  and  vanillin  dissolved  in  absolute  alcohol,  and 
the  latter  of  dimothylamino-azo-benzene. 

The  first  amount  of  hydrochloric  acid  secreted  usually  gives  a  negative  reaction 
with  these  reagents,  because  it  is  bound  by  the  albuminous  bodies  to  form  acid 
albuminates.  Furthermore,  while  pure  gastric  juice  contains  no  lactic  acid,  this 
acid  is  always  present  in  the  gastric  contents  composed  of  the  pure  juice  and  a 
mixture  of  partly  digested  food.  It  arises  in  consequence  of  the  fermentation  of 
carbohydrates  which  are  attacked  by  the  bacillus  lactici  ingested  with  the  food, 
and  are  converted  into  sugar  and  lactic  acid.  Under  ordinary  conditions,  however, 
the  action  of  this  bacillus  is  cut  short  by  the  hydrochloric  acid,  because  even  an 
acidity  of  only  0.07  to  0.08  per  cent.  HCl  absolutely  prevents  the  formation  of 
lactic  acid  from  dextrose.  Consequently,  lactic  acid  must  be  formed  chiefly  during 
the  early  stages  of  gastric  digestion  or  when  there  is  a  deficiency  in  hydrochloric 
acid,  as  during  carcinomatous  affections  of  the  stomach.  But  naturally,  the  acidity 
of  normal  gastric  juice  is  not  due  to  lactic  acid,  as  may  be  proved  by  taking  this 
acid  up  with  ether  and  applying  Uffelmann's  test|_^to  the  extract. 

Pepsin  (Th.  Schwann,  1836)  is  not  present  in  the  cells  of  the  gastric  glands  as 
such,  but  in  its  inactive  form,  known  as  stored  pepsin  or  pepsinogen. i  The  latter, 
therefore,  may  be  regarded  as  the  precursor  or  mother-substance  of  this  ferment 
which  assumes  its  active  condition  only  after  its  escape  from  the  cells  and  in  the 
presence  of  hydrochloric  acid.  This  is  proved  by  the  fact  that  the  riiucous  mem- 
brane of  the  dog  or  pig,  which  is  alkaline  or  neutral  in  reaction,  may  be  extracted 
with  water  and  mixed  with  hydrochloric  or  some  other  acid  (0.3  percent.)  to  form 
a  powerful  digestive  medium.  Contrariwise,  gastric  mucosa  extracted  under 
glycerin  may  be  kept  for  some  time  without  any  indication  of  self-digestion  or 
autolysis.  This  process,  however,  sets  in  immediately  if  an  acid  is  added  to  this 
extract.  Furthermore,  Langley^  has  shown  that  pepsin  is  very  sensitive  to 
alkalies,  because  when  neutralized  with  sodium  hydrate  and  again  acidified,  it  loses 
much  of  its  former  potency.  An  extract  of  the  mucosa,  however,  may  be  made 
slightly  alkaline  for  a  short  time  without  losing  its  activity  on  acidification,  while 
an  acid  extract  cannot  be  made  alkaline  without  permanently  destroying  its  power. 
Another  means  of  showing  that  the  substance  contained  in  the  gastric  cells  is 
different  from  actual  pepsin,  is  furnished  by  the  fact  that  carbonic  anhydrid 
gas  destroys  the  action  of  the  pepsinogen  contained  in  a  neutral  aqueous  extract 
of  frog's  esophagus.  Contrariwise,  if  this  extract  is  first  acidified  and  then 
neutralized,  the  passage  of  carbonic  anhydrid  through  it  does  not  nullify  its 
power. 

Pepsin  is  a  colloidal  substance.  As  such  it  is  not  dialyzed  through  animal 
membranes  or  parchment  paper.  Regarding  its  chemical  nature  we  know  very 
little.  Pekelharing2  and  Nencki  and  Lieber*  classify  it  as  a  protein  or  protein- 
like body  of  the  elementary  composition:  C,  51.26  per  cent.,  H,  6.74  per  cent., 
N,  14.33  per  cent.,  and  S,  1.5  per  cent.  It  should  be  remembered,  however,  that 
this  ferment  varies  in  its  composition  in  different  animals,  because  it  presents 
not  only  certain  differences  in  the  optimum  concentration  of  the  acid  required  to 
activate  it,  but  also  in  its  resistance  to  heat.  The  question  of  what  becomes  of  the 
pepsin  after  it  has  unfolded  its  ferment-action,  cannot  be  answered  with  certainty. 
The  probability  is  that  the  largest  amount  of  it  is  destroyed  in  the  intestine  by  the 
other  enzymes  or  by  the  bacteria,  but  a  small  portion  of  it  may  also  be  absorbed 
and  enter  the  blood  and  urine. 

Rennin. — The  gastric  juice  of  mammals,  as  well  as  aqueous  infusions  of  the 
gastric  mucosa,  possesses  the  property  of  curdling  milk.  This  process  is  essentially 
a  coagulation  during  which  a  soluble  protein  contained  in  milk  is  converted  into  its 

^  Hammarsten,  Zeitschr.  fiir  Physiol.  Chemie,  xcii,  1914,  121. 

2  Jour,  of  Physiol,  vii.  1886,  371. 

^  Zeitschr.  fiir  physiol.  Chemie,  xxxv,  1902,  8 

*  Ibid.,  xxxii,  1901,  261. 


THE    DIGESTIVE    SECRETIONS  925 

insoluble  form.  The  active  aRont  concerned  in  this  change  is  an  enzyme,  known  as 
rennin,  rennet  or  chyniosin.  Like  pepsin,  this  substance  its  produced  by  the  chief 
cells,  being  stored  in  them  in  its  inactive  form  as  prorennin  or  prochymosin. 
Wlien  passed  into  the  tlucts,  it  assumes  its  cliaracteristic  action  of  clotting  milk, 
but  only  in  tlie  presence  of  calcium  and  hydrochloric  acid.  Chemically,  this  process 
consists  in  a  conversion  of  the  soluble  caseinogen  of  milk  into  the  insoluble  casein. 
Together  witli  the  other  proteins,  the  latter  is  then  subjected  to  the  proteolytic 
action  of  the  pepsin. 

Rennin,  liowever,  is  not  the  only  milk-clotting  enzyme.  Similar  bodies  are 
present  in  the  pancreatic  juice,  the  intestinal  juice,  the  juices  of  certain  fruits,  such 
as  the  cocoanut  and  the  pineapple,  and  in  many  V)acteria.  In  fact,  since  the 
curdling  of  milk  is  a  common  phenomenon  of  proteolytic  proces.ses  anywhere  in 
nature,  some  authors  l)elieve  that  it  is  not  caused  by  a  specific  enzyme  but  by  the 
proteolytic  ferment  itself.  Opposed  to  this  view  is  the  less  probable  one  that  a 
special  non-proteolytic  coagulating  substance  is  almost  universally  present  in 
nature.' 

This  controversy  brings  up  the  question  pertaining  to  the  possible  identity  of 
rennin  and  pepsin,  which  must  still  be  considered  as  not  definitely  settled.  To  be 
sure.  Hammarsten  has  shown  that  pepsin  in  its  pure  form  possesses  coagulating 
properties,  but  certain  facts  are  also  at  hand  to  prove  that  rennin  and  pepsin  are 
very  unlike  one  another. '  If  it  is  assumed  that  the  clotting  of  milk  is  a  general 
property  of  all  proteolytic  enzymes,  the  stomach  must  contain  two  such  agents, 
namely  pepsin  and  rennin.  The  former  is  a  product  of  the  fundic  glands  and  is 
activated  only  in  an  acid  medium.  The  latter,  on  the  other  hand,  is  chiefly  a 
product  of  the  pj^loric  glands  and  acts  in  an  acid  as  well  as  in  a  neutral  medium. 
In  this  regard,  therefore,  it  is  more  like  the  trypsin  of  the  pancreatic  juice  and  the 
erepsin  of  the  intestinal  secretion.  As  is  usual  with  many  biological  properties, 
these  enzymes  are  unequally  distributed  in  different  animals  and  undergo  changes 
in  their  potency  even  in  the  same  animal.  Thus,  we  find  that  rennin  is  especially 
abundant  in  the  stomachs  of  suckling  animals,  and  that  its  amount  or  potency  gradu- 
ally diminishes  in  later  years  and  particularly  in  the  carnivora.  Its  place  is  then 
taken  by  the  pepsin  which  acts  in  an  acid  medium  at  a  time  when  the  adult  stomach 
has  acquired  a  much  greater  resistance  than  it  possesses  shortly  after  birth. 

In  addition,  gastric  juice  contains  a  fat-splitting  ferment  or  lipase  which  pos- 
sesses the  property  of  splitting  emulsified  neutral  fats  into  glycerin  and  fatty  acids.^ 
Such  fats  are  present  in  milk.  The  non-emulsified  fat,  on  the  other  hand,  it  allows 
to  traverse  the  stomach  practically  unchanged.  This  lipase  exists  in  the  mucosa 
in  the  form  of  a  mother-substance.  The  fact  that  it  is  of  much  greater  importance 
in  the  suckling  than  in  the  adult  is  in  accordance  with  the  character  of  the  food 
of  the  young,  which  consists  largely  of  emulsified  fat. 

The  Resistance  of  the  Stomach  to  the  Gastric  Ferments. — Since 
the  proteolytic  ferment  pepsin  acts  in  an  acid  medium,  it  may  seem 
strange  that  the  gastric  wall  is  normally  exempt  from  its  digestive 
power,  while  a  stomach  which  has  been  rendered  abnormal  by  inter- 
fering with  its  blood-supply,  rapidly  undergoes  autolytic  changes. 
This  is  also  true  of  the  excised  organ  when  immersed  in  its  own  juice. 
A  number  of  theories  have  been  advanced  in  explanation  of  the.se  facts, 
all  of  which  embody  the  belief  that  the  lining  cells  of  the  stomach  are 
normally  resistant  against  the  gastric  juice.  Thus,  it  has  been  stated 
that   the  surface  of  the  stomach  is  always  covered  with  a  layer  of 

1  Schmidt-Xielson,  Zeitschr.  fiir  physiol.  Chemie,  xlviii,  1906,  92;  Fuld,  Ergebn. 
der  Phvsiol.,  i,  1902;  and  Pawlow  and  Pavutschuk,  Zeitschr.  flir  phj'sik.  Chemie, 
xlii,  1904,  41.5. 

2  Volhard,  Zeitschr.  fiir  klin.  Med.,  xlii,  1900,  414. 


926  THE    EXTERNAL    SECRETIONS 

mucus  which  acts  as  a  protection  for  the  underlying  cells.  In  prac- 
tically all  cases  of  hyperchlorhydria,  however,  the  secretion  of  mucus 
is  greatly  diminished,  without  thus  creating  an  especially  favorable 
condition  for  the  formation  of  ulcers.  Contrariwise,  mucus  may  be 
secreted  in  excessive  amounts  in  the  presence  of  formidable  ulcers. 
Another  theory  holds  that  the  aforesaid  resistance  of  the  gastric  wall 
is  due  to  the  alkalinity  of  its  constituent  cells  which  tends  to  neutralize 
the  gastric  juice  anointing  them.  Going  a  step  farther  in  this  direc- 
tion, we  might  say  that  the  cause  of  the  resistance  of  the  gastric 
mucosa  against  digestion  lies  in  the  normality  of  its  life  processes.  The 
latter  consist  in  oxidations,  and  hence,  it  is  evident  that  the  pepsin 
immediately  exposed  to  them  must  be  rendered  inert  by  being  oxidized. 
In  this  connection  it  is  of  interest  to  note  that  the  cells  of  the  gastric 
mucosa  possess  an  intense  power  of  oxidation.  This  observation 
of  Lillie^  is  in  accord  with  that  of  Burge,^  proving  that  pepsin  is  easily 
destroyed  by  oxidation.  Under  normal  conditions,  therefore,  a 
balance  is  established  between  the  intracellular  oxidations  and  the 
digestive  action  of  the  neighboring  pepsin.  Whenever  this  balance 
is  destroyed,  the  cells  are  digested  with  the  formation  of  erosions  of 
varying  size. 

These  oxidative  processes  may  be  disturbed  in  different  ways; 
for  example,  by  cutting  off  the  blood  supply  of  a  particular  area  of 
the  stomach  or  by  depressing  the  circulatory  efficiency  of  the  animal 
as  a  whole.  Thus,  a  local  anemia  may  be  established  in  consequence 
of  tumors,  wounds,  stricture  of  the  pylorus  and  thrombosis;  and  a 
general  circulatory  deficiency  in  consequence  of  hemorrhage,  anemia, 
poisons  and  toxins. 

The  Regulation  of  the  Secretion  of  Gastric  Juice  by  Hormones 
and  Vitamines. — In  general,  it  may  be  said  that  glands  may  be  made 
to  secrete  in  two  ways,  namely,  indirectly  by  means  of  chemical  agents 
contained  in  the  blood,  and  directly  by  the  stunulation  of  the  nerve 
fibers  innervating  the  different  cells.  Eventually,  of  course,  both  types 
of  stimuli  are  conveyed  to  the  cells,  exciting  their  cytoplasm  at  first 
hand.  Agents  which  possess  this  stmiulating  action,  most  generally 
arise  elsewhere  in  the  body  and  are  brought  to  the  gland  in  the  blood- 
stream. Thus,  it  has  been  found  that  the  pituitary  body  gives  rise 
to  an  internal  secretion  which  increases  the  flow  of  milk  from  the 
mammary  gland,  and  that  the  lining  of  the  duodenum  produces  an 
agent  which  initiates  the  flow  of  pancreatic  juice.  As  far  as  the  stom- 
ach is  concerned,  Edkins^  has  shown  that  the  injection  into  the  blood- 
stream of  broth,  dextrin,  peptone  or  acid  does  not  augment  the  flow 
of  gastric  juice,  while  an  extract  of  the  mucous  membrane  of  the 
pylorus  invariably  acts  as  a  potent  secretogogue.  It  is  evident,  there- 
fore,  that  the  mucosa  of  the  stomach  produces  a  hormone,  known 

1  Am.  Jour,  of  Physiol.,  vii,  1902,  413. 

2ibid.,xxxvii.  1915.  462. 

3  Jour,  of  Physiol,  xxxiv,  1906,  133. 


THE    DIGESTIVE    SECRETIONS  927 

as  (jastric  secretin,  or  (idslrin,  which  is  HbcralcMl  (hnin^  llic  process 
of  Kii-"'tJ"ic  (hfi;('stion  and  serves  as  a  sthuiilus  to  the  local  glands. 
Secondly,  it  cannot  be  doubted  that  food  itself  contains  certain 
stimulating  substances  which  upon  their  absorption  exert  a  definite 
synthetic  or  constructive  influence  upon  all  cellular  processes.  These 
accessory  bodies  are  known  as  ritannnes.  Practically  nothing  is 
known  regarding  their  chemical  nature/  but  we  divide  them  as  a  rule 
into  two  groups,  viz. :  those  soluble  in  fat  which  are  abundant  in  but- 
ter,^ and  those  soluble  in  water  and  alcohol  which  are  present  in  wheat, 
maize,  cabbage,  and  in  many  foods  of  animal  origin. 

It  must  seem  strange  that  an  animal  fed  upon  a  mixture  of  pure  proteins, 
fats,  carbohydrates,  salts  and  water,  will  not  thrive,  but  ceases  to  develop  and  pres- 
ently exhibits  a  complex  of  symptoms  indicative  of  malnutrition.  But  if  this 
artificial  diet  is  augmented  by  some  natural  food,  such  as  vegetables  or  milk,  the 
animal  immediately  begins  to  develop  normally.  Hopkins^  divided  a  large  number 
of  young  rats  into  two  groups,  one  of  which  received  a  diet  of  caseinogen,  fats, 
carbohydrates  and  salts,  and  the  other  the  same  food  plus  a  small  ration  of  fresh 
milk.  Although  the  consumption  of  material  was  practically  the  same  in  both 
groups  of  animals,  the  former  soon  ceased  growing,  while  the  latter  developed 
normally.  Even  man  may  suffer  from  these  "deficiency-diseases,"  chief  among 
which  are  scurvy,  beri-beri,  pellagra  and  rickets.  Scurvy,  for  example,  used  to  be 
prevalent  upon  sailing  vessels  when  fresh  meat,  vegetables  and  fruits  were  unob- 
tainable, and  when  fish  formed  the  almost  constant  diet.  As  a  means  of  preventing 
this  disease,  lime  or  lemon  juice  was  generally  given,  it  being  believed  that  citric 
acid  and  traces  of  malic  acid  are  essential  constituents  of  food.  Scurvy  may  also 
develop  in  infants  fed  exclusively  on  pasteurized  milk.  All  the  alarming  symptoms 
of  this  disease  may  be  made  to  disappear  in  the  course  of  a  day  or  two  by  the  use 
of  fresh  milk  or  by  the  addition  of  orange  juice  and  the  white  of  egg  to  the  former. 

Very  similar  disturbances  of  nutrition  may  be  incited  by  the  exclusive  use 
of  polished  rice.  Thus,  it  has  been  noted  in  Japan  that  Kak-Ka  (beri-beri)  has 
greatly  increased  since  the  primitive  mill-stones  have  been  displaced  by  the 
modern  steel-rollers.  In  Bengal,  on  the  other  hand,  where  the  old  methods  of 
milling  are  still  in  use,  this  disease  is  practically  unknown,  although  rice  forms  one 
of  the  chief  foods  of  this  country.  A  similar  disease  may  be  evoked  in  birds  by 
feeding  them  only  polished  rice.  This  puzzling  situation  has  been  cleared  up  in  a 
large  measure  by  Funk,''  who  has  extracted  from  the  polishings,  i.e.,  from  the 
outer  coats  of  the  rice  kernel,  a  basic  principle  which  he  calls  vitamine.  Further- 
more, it  has  been  found  that  if  these  polishings,  or  their  alcoholic  extract,  are  added 
to  the  rice  prepared  in  the  modern  way,  this  food  does  not  produce  the  aforesaid 
disease.  After  its  development,  the  latter  may  be  quickly  remedied  by  the  in- 
•  gestion  of  unpolished  rice  or  by  eating  potatoes,  fresh  vegetables,  fruit,  milk,  meat 
and  eggs.  Yeast  is  said  to  contain  vitamines  in  considerable  amovmts  and  it  is 
assumed  that  the  nutritive  value  of  fermented  beverages,  such  as  beer,  is  in  large 
part  due  to  these  bodies.  Quite  similarly,  it  is  assumed  that  the  value  of  whole- 
meal bread  does  not  depend  upon  its  extra  amount  of  protein  but  probably  upon 
its  content  in  vitamines. 

It  must  be  concluded,  therefore,  that  the  different  foods  taken  into 
the  stomach  contain  certain  substances  which  in  themselves  cannot 
be  regarded  as  foods  nor  as  condiments,   but  which  are  absolutely 

1  McCoUum,  Simmonds  and  Fitz,  Am.  Jour,  of  Physiol.,  Ixi,  1916,   361. 

2  Osborne  and  Mendel,  Jour,  of  Biol.  Chem.,  xxiv,  1916,  37. 

3  Jour,  of  Physiol.,  xliv,  1912,  425. 

4  Ergebn.  der  Physiol.,  1913,  124. 


928  THE    EXTERNAL    SECRETIONS 

essential  for  the  maintenance  of  healtii  and  growth.  While  as  yet 
chemically  unrecognized,  their  presence  has  been  proved  by  physiolog- 
ical means.  They  play  the  part  of  "building  stones"  in  the  syntheses 
of  the  developing  animal.  As  such,  they  act  upon  the  secretory  proc- 
esses as  well  as  upon  the  processes  of  assimilation  and  dissimilation. 
Consequently,  they  must  unfold  their  function  as  secretogogues  shortly 
after  their  entrance  into  the  digestive  tract,  and  must  also  exert  a 
certain  influence  upon  the  activity  of  the  gastric  glands.  This  end 
they  accomplish  (a)  by  stimulating  the  cells  of  the  gastric  glands 
directly,  (6)  by  entering  the  blood  and  influencing  the  secretory  ac- 
tivity of  these  glands  in  an  indirect  way,  and  (c)  by  causing  a  liberation 
of  gastric  secretin  which  in  turn  affects  the  glandular  elements. 

The  Nervous  Control  of  the  Secretion  of  Gastric  Juice. — Like 
saliva,  gastric  juice  is  secreted  continuously,  but  only  in  amounts  suf- 
ficient to  lubricate  the  mucous  surfaces.  At  various  times,  however, 
a  more  copious  flow  is  initiated  which  finds  its  origin  in  stimuli  of  an 
occasional  character.  The  latter  embrace  (a)  chemical  agents  which 
reach  the  gastric  cells  either  directly  from  the  cavity  of  the  stomach  or 
indirectly  by  the  blood,  and  (6)  stimuli  which  act  reflexly  through 
particular  reflex  circuits.  It  must  be  evident,  however,  that  these 
reflex  arcs  need  not  be  situated  in  the  stomach,  at  least  not  their 
afferent  path,  or  analyzer,  because  a  secretion  of  gastric  juice  results 
not  only  in  consequence  of  the  entrance  of  food  into  the  stomach,  but 
also  upon  its  being  taken  into  the  mouth;  in  fact,  even  the  mere  sight 
and  smell  of  nutritive  substances  may  serve  as  an  efficient  stimulus. 
The  act  of  chewing,  however,  does  not  serve  as  a  stimulant,  nor  does 
the  intake  of  an  indifferent  substance  not  related  to  food.  Conse- 
quently, we  may  say  that  the  secretion  of  gastric  juice  is  controlled 
by  nerve  impulses  of  intragastric  and  extragastric  origin  produced  by 
palatable  substances. 

This  statement  implies  that  the  afferent  side  of  the  reflex  circuit 
concerned  in  gastric  secretion  is  diversified,  while  the  efferent  side  is 
not.  Relative  to  the  latter,  it  has  been  proved  that  it  is  contained  in 
the  vagus  system,  because  the  division  of  the  ventral  and  dorsal  vagi 
below  the  origins  of  their  pulmonary  and  cardiac  branches  abolishes 
this  reflex,  while  the  stimulation  of  the  distal  end  of  either  nerve 
is  followed  by  a  secretion.  In  addition,  it  has  been  stated  that  these 
nerves  contain  musculomotor  fibers  for  the  stomach.^  The  splanchnic 
nerves  do  not  seem  to  be  involved  in  this  secretory  reaction,  because 
their  division  and  stimulation  remains  without  effect.  We  know, 
however;  that  these  nerves  embrace  vasomotor  fibers  for  the  stomach 
which  traverse  the  ganglia  of  the  solar  plexus  and  reach  this  organ  by 
following  the  highways  of  the  different  gastric  arteries.  Consequently, 
since  their  stimulation  must  lead  to  a  constriction  of  the  gastric  blood- 
vessels, they  must  limit  the  quantity  of  the  gastric  juice,  but  in  an  in- 
direct way  and  not  as  secretory  nerves.     Now,  since  their  action  is 

1  Burton-Opitz,  Pfliiger's  Archiv,  cxxxv,  1910,  205. 


THE    DIGESTrV'E    SECRETIONS  929 

not  inhibito-socrctory  in  its  nature,  they  cannot  be  considered  as 
forming  a  part  of  an  inliibitor  mechanism  which  acts  antagonistically 
to  the  vagi  nerves.  The  latter  are  secretomotors,.  It  seems,  therefore, 
that  the  vagi  nerves  arc  capable  of  stimulating  as  well  as  of  inhibiting 
the  flow  of  the  gastric  juice,  and  hence,  they  must  form  the  chief 
efferent  secretory  path  Ix'twc'cn  the  central  nervous  system  and  the 
stomach. 

In  considering  the  effects  of  the  intragastric  stimuli,  we  are  con- 
fronted by  the  statement  that  the  mechanical  stimulation  of  the  gastric 
m«cosa  produces  only  a  discharge  of  mucus  and  not  of  gastric  juice. 
Even  water  and  meat,  when  introduced  through  a  fistula,  give  rise 
to  only  a  slight  flow.  The  same  is  true  of  bread  and  coagulated  white 
of  egg,  and  especially  if  these  substances  are  introduced  while  the 
animal  is  sleeping.  Of  particular  interest  is  the  long  latent  period  then 
intervening  between  the  moment  of  feeding  and  the  time  when  the 
first  drop  of  gastric  juice  is  obtained.  Even  in  the  case  of  raw  meat, 
15  to  45  minutes  may  elapse  before  the  secretion  actually  tegins,  but  a 
somewhat  quicker  reaction  may  be  evoked  by  giving  these  substances 
in  a  semi-digested  condition,  because  the  purely  nervous  excitation 
is  then  augmented  by  the  liberation  of  chemical  bodies  in  the  form  of 
vitamines  and  hormones  which  stimulate  the  gastric  glands  either 
directly  or  through  the  blood. 

A  slight  secretion  of  gastric  juice  is  also  obtained  after  the  stomach 
has  been  isolated  from  the  central  nervous  system  by  the  division 
of  all  of  its  nerves,  namely,  the  vagi  and  splanchnic  nerves  and  the  com- 
municating rami  of  the  latter.  Consequently,  this  organ  must  be  in 
possession  of  a  local  reflex  mechanism  which  under  ordinary  conditions 
is  controlled  directly  by  the  central  nervous  system.  In  other  words, 
inasmuch  as  the  stomach  is  a  typical  autonomic  organ,  the  higher 
centers  merely  alter  its  activity  in  accordance  with  the  functional 
requirements  of  other  parts  of  the  body.  Impulses  are  relayed  to  it 
which  either  increase  or  decrease  the  flow  of  gastric  juice. 

These  data  tend  to  show  that  the  direct  stimulation  of  the  gastric 
receptors  is  not  a  very  efficient  means  of  evoking  a  secretion  of  gastric 
juice.  Much  better  results  may  be  obtained  by  influencing  the  local 
mechanism  through  a  more  general  mechanism  which  is  capable  of 
introducing  what  is  termed  the  psychical  element,  or  appetite.  As 
long  ago  as  1852,  Bidder  and  Schmidt  observed  that  a  copious  secre- 
tion of  gastric  juice  may  be  evoked  in  a  dog  with  a  gastric  fistula  by 
simply  allowing  him  to  obtain  a  visual  impression  of  the  food.  Some 
years  later  Richet  obtained  the  same  results  in  a  boy  whose  esophagus 
had  been  completely  closed  by  a  cicatrix  formed  in  consequence  of 
an  erosion  by  a  strong  alkali.  Since  that  time  this  observation  has 
been  repeated  a  large  number  of  times  both  upon  human  beings  with 
gastric  fistulas  as  well  as  upon  different  mammals  with  diverticulated 
stomachs.     Another  procedure  which  has  led  to  valuable  results  is 

59 


930  THE    EXTERNAL    SECRETIONS 

the  method  of  sham-feeding.^  Having  established  a  gastric  fistula, 
the  esophagus  is  divided  in  the  neck  and  its  two  cut  ends  securely- 
fastened  to  the  edgas  of  the  wound.  The  animals  so  changed  soon 
accommodate  themselves  to  their  new  conditions  and  can  then  be  sub- 
jected to: 

(a)  Actual  feeding  through  the  distal  orifice  of  esophagus. 

(b)  Sham-feeding,  by  allowing  them  to  masticate  the  food  in  the 
usual  way,  although  it  again  reaches  the  outside  through  the  opening 
in  the  neck. 

(c)  Psychical  feeding,  in  which  the  animal  is  merely  allowed 
to  see  or  to  smell  the  food  without  actually  ingesting  it. 

The  importance  of  the  psychical  element  in  the  formation  of  gas- 
tric juice  may  be  proved  in  various  ways.^  Thus,  it  suffices  to  allow 
the  hungry  animal  to  see  the  food;  moreover,  the  secretion  then  ob- 
tained is  usually  more  copious  than  if  secreted  without  the  help  of 
psychic  impressions.  For  example,  if  two  dogs  are  fed  weighed  amounts 
of  meat  through  fistulas,  without  their  knowledge,  a  certain  quantity 
of  gastric  juice  will  be  secreted  by  each,  but  if  one  of  these  animals  is 
now  given  a  sham  meal  of  meat,  the  amount  of  protein  digested  by  it 
in  a  given  period  of  time  will  be  five  times  greater  than  that  digested 
by  the  other  animal  not  psychically  stimulated.  Those  investigators 
who  have  studied  the  effects  of  gastric  fistulae  in  human  beings,  have 
made  similar  observations  and  maintain  that  the  seeing,  smelling  and 
thinking  of  palatable  food,  as  well  as  the  leisurely  mastication  of  sapid 
substances,  give  rise  to  a  copious  flow  of  gastric  juice.  Appetite 
is  a  potent  factor  in  this  process  and  so  is  the  quality  of  the  food.  Food 
and  condiments  which  the  individual  liked  especially,  were  more 
effective  than,  say,  butter,  bread  and  meat.  This  fact  may  serve  as 
a  reason  for  the  ingestion  of  a  palatable  dessert,  salad,  or  fruit  at  the 
end  of  a  meal.  The  purpose  of  these  "appetizers"  is  to  augment  and 
to  prolong  the  appetite  secretion  of  gastric  juice. ^ 

The  fact  to  be  deduced  from  these  experiments  is  that  the  different 
kinds  of  food  possess  an  almost  specific  stimulating  power  which  en- 
ables them  to  vary  not  only  the  quantity  of  the  gastric  juice,  but  also 
the  length  of  the  period  intervening  between  their  ingestion  and  the 
appearance  of  the  secretion.  In  the  case  of  saliva  it  is  easily  observed 
that  this  latent  period  is  short,  a  fact  which  is  in  keeping  with  func- 
tional requirements.  Evidently,  since  the  food  enters  the  mouth 
quickly  and  remains  here  for  only  a  relatively  short  period,  it  is 
essential  that  this  secretion  be  produced  in  the  shortest  possible 
time.  In  the  case  of  gastric  juice  an  urgency  of  this  kind  does  not 
exist  and  hence,   the  latent  period  may  be  appreciably  prolonged. 

1  Pawlow  and  Schumowa-Simanowskaja,  Zentralbl.  fiir  Physiol.,  iii,  1889. 

^  Bogen,  Pfliiger's  Archiv,  cxvii,  1907. 

'  Rabinowitch,  Dissertation,  Giessen,  1907  (spices);  Pinkussohn,  Miinch.  med. 
Wochenschr.,  1906  (coffee  and  cocoa) ;  Kast,  Archiv  fiir  Verdauungskr.,  xii  (alcohol) ; 
Bickel,  Berliner  klin.  Wochenschr.,  1906  (mineral  waters). 


THE    DIGESTIVE    SECRETIONS  931 

Thus,  a  moat  diot  does  not  givo  a  maximum  rato  of  secretion  until  the 
end  of  the  first  or  second  hour,  while  a  bread  diet  produces  its  secretory- 
climax  during  the  first  hour,  and  a  milk  diet  during  the  second  and  third 
hours.  Quite  similarly,  larf^e  (luantities  of  oil  diminish  the  secre- 
tion considerably,  while  starch,  fat,  and  white  of  egg  are  practically 
inert.  It  has  also  been  observed  that  meat-juice  is  a  more  efficient 
stimulus  than  bread-juice,  while  milk-juice  occupies  in  this  regard  an 
intermediate  position.  Contrariwise,  bread-juice  contains  a  more 
abundant  quantity  of  ferment  than  meat-juice.  Among  the  influences 
which  depress  the  secretion  of  gastric  juice  might  be  mentioned  un- 
pleasant emotions,  such  as  anger,  and  fear.  Thus,  it  has  been  noted 
that  dogs  with  gastric  fistulas  cease  secreting  when  confronted  by  a 
cat,  and  we  are  all  well  aware  of  the  fact  that  a  clear  conscience 
and  untroubled  mind  are  essential  prerequisites  for  an  efficient  gastric 
digestion. 

While  it  is  difficult  to  combine  these  facts  into  a  brief  story  of 
events,  it  may  be  stated  that  the  normal  secretion  of  gastric  juice  is 
dependent  upon  two  factors,  namely,  upon  an  immediate  nervous  and 
a  latent  chemical  stimulus.  The  former  finds  its  origin  in  the  exci- 
tation of  the  receptors  of  the  oral  cavity  as  well  as  of  certain  extero- 
ceptors,  such  as  the  retinae  and  the  olfactory  cells,  and  its  purpose  is 
to  produce  a  flow  of  gastric  juice  in  as  short  a  time  as  possible  after  the 
ingestion  of  the  food.  This  gives  rise  to  what  has  been  termed  the 
appetite  secretion.  The  purpose  of  the  second  factor  is  to  maintain 
this  secretion  after  it  has  been  initiated.  In  the  latter  instance,  the 
stimulus  is  of  intragastric  origin,  and  is  evoked  by  the  vitamines  of  the 
food  and  the  specific  hormone,  gastrin.  The  most  important  reaction 
is  the  first,  or  appetite  secretion,  because  it  serves  to  establish  a  diges- 
tive medium  for  those  food  stuffs  which  in  themselves  are  very  inef- 
ficient gastric  stimulants.  In  accordance  with  this  sequence  of  events, 
it  may  be  said  that  the  gastric  juice  which  is  secreted  in  the  course  of  a 
meal,  consists  of  two  portions,  namely,  (a)  an  initial  amount  which 
is  poured  forth  within  5  minutes  after  the  ingestion  of  the  food  and 
which  is  due  to  a  reflex  stimulation,  and  (6)  a  latent  amount,  the  secre- 
tion of  which  follows  the  chemical  stimulation  by  the  food  after  it  has 
entered  the  stomach. 

The  Duodenal  Juice. — Beginning  at  the  pylorus,  the  gastric 
glands  gradually  pass  over  into  the  glands  of  Brunner.  The  latter  are 
imbedded  in  the  submucous  coat,  and  appear  as  branched  and  con- 
voluted tubes,  the  ducts  of  which  open  free  upon  the  mucous  surface. 
In  the  carnivora,  they  occupy  an  area  extending  about  3  to  5  cm. 
below  the  pylorus,  while  in  the  herbivora  they  reach  to  a  line  about 
15  cm.  below  this  point.  The  secretion  furnished  by  them  is  known 
as  the  duodenal  juice.  It  is  alkaline  in  reaction,  owing  to  its  content 
in  carbonates,  and  effervesces  strongly  when  brought  in  contact  with 
an  acid.  Its  action  as  a  digestive  juice  is  not  important,  although  it 
contains    some  invertin  which  inverts  cane-sugar,   as  well  as  some 


932 


THE    EXTERNAL    SECRETIONS 


erepsin.  Its  importance  lies  rather  in  the  fact  that  it  gives  lodgment 
to  a  substance,  known  as  enter okinase,^  which  possesses  the  power  of 
greatly  augmenting  the  action  of  the  pancreatic  juice  on  proteins.  In 
the  absence  of  this  secretion,  following,  for  example,  the  resection 
of  extensive  segments  of  the  duodenum,  serious  digestive  disturbances 
result;  in  fact,  it  is  commonly  stated  that  this  operation  is  fatal  for 
reasons  not  fully  understood.  It  is  supposed,  however, that  it  converts 
the  inactive  trypsinogen  into  the  powerful  proteolytic  agent  trypsin 
A  similar  activating  enzyme  has  been  abstracted  from  the  spleen 
(Mendel),  but  it  has  not  been  proved  that  this  organ  exerts  this  par- 
ticular function  under  normal  conditions. 

The  Pancreas. — This  gland  is  tubulo-racemose  in  its  character, 
the  individual  acini  being  separated  from  one  another  by  a  loose  net- 


FiG.  495. — DiAGR,\]vi  TO  Show  the  Position  of  the  Ducts  of  the  Pancreas. 
D,  Duodenum ;P,  pancreas;  DC,  ductus  choledochus;  DW ,  ductus  Wirsungianus; 
DS,  ductus  Santorini. 


work  of  connective  tissue  in  which  are  imbedded  small  groups  of 
spindle-shaped  cells  forming  the  so-called  islets  of  Langerhans.  It 
will  be  brought  out  later  on  that  these  cells  furnish  an  internal  secre- 
tion which  has  to  do  with  the  metabolism  of  the  carbohydrates.  For 
the  present  we  are  concerned  solely  with  the  true  secretory  cells  of  this 
organ,  forming  the  typical  tubular  acini  and  producing  the  "external" 
secretion  known  as  the  pancreatic  juice.  These  cells  are  polyhedral 
in  shape  and  exhibit  two  zones,  namely,  a  clear  outer  and  a  granular 
inner.  Their  strongly  basophile  nuclei  occupy  a  central  position 
within  their  cytoplasm. 

It  will  be  remembered  that  this  organ  forms  a  narrow  band  of  tissue,  the  central 
portion  of  which  partially  envelops  the  duodenum,  while  its  caput  and  cauda  extend 
for  some  distance  into  the  mesentery.  Its  principal  excretory  channel  is  the  pan- 
creatic duct  or  duct  of  Wirsung,  which  opens  into  the  duodenum  about  10  to  12  cm. 
below  the  sphincter  of  the  pylorus.  A  smaller  duct  may  also  be  present,  which  is 
known  as  the  duet  of  Santorini  and  drains  the  head-region  of  this  organ,  entering 

^  Chepowalnikow,  Dissertation,  St.  Petersburgh,  1899. 


THE    DIGESTIVE    SECRETIONS 


933 


the  duodenum  separately  at  a  distance  of  2  to  3  cm.  above  the  former.*  In  some 
animals  the  duct  of  Wirsung  unites  with  the  common  bile  duct  shortly  before  its 
entrance  into  the  duodenum.  This  accounts  for  the  fact  that  tumors,  afTectinj^ 
the  head  and  body  of  the  pancreas,  very  frequently  give  rise  to  a  stagnation  of  the 
bile.  Thus,  a  slowly  developing  jaundice,  which  is  a.ssociated  with  a  loss  of  appetite 
and  indigestion,  but  no  pain,  almost  always  indicates  a  carcinoma  of  the  pancreas. 
In  the  dog,  the  blood-supply  of  the  pancreas  is  derived  from  the  mesenteric, 
pancreatico<luodenal  and  splenic  arteries.  The  first  supplies  its  head-region, 
the  second  its  body,  and  the  third  its  tail.  The  venous  return  is  effected  by  three 
channels  of  which  the  vena  pancreatica  is  the  largest.  The  latter  joins  the  portal 
vein  a  short  distance  below  thehilum  of  the  liver.  A  small  portion  of  its  blood  is 
returned  by  way  of  the  splenic  and  mesenteric  veins,  but  this  also  enters  the  portal 
vein.  The  nerve-fibers  innervating  this  organ  arise  in  the  mesenteric  and  celiac 
ganglia  of  the  solar  plexus  and  follow  the  highways  of  the  aforesaid  arteries.  Pre- 
ganglionically,  connection  is  made  with  the  central  nervous  system  by  way  of 
the  vagi  and  splanchnic  nerves. 

Histological  Changes  in  the  Cells  of  the  Pancreas  During  Secre- 
tion.— In  1856  CI.  Bernard  observed  in  fresh  preparations  of  the  pan- 


FiG.  496. — A  Terminal  Lobule  of  the  Pancre,\s  of  the  Rabbit.     (Kuhne  and  Sheridan 

Lea.) 
A,  in  resting  condition;  B,  after  active  secretion. 

creas  of  the  rabbit  that  two-thirds  of  the  inner  zone  of  its  cells  are 
taken  up  by  a  dense  granular  material  which  he  believed  to  be  the 
mother-substance  of  the  active  principles  of  the  pancreatic  juice. 
Later  on  Kiihne  and  Lea^  succeeded  in  showing  that  the  activity  of 
this  gland  is  associated  with  a  loss  of  at  least  a  part  of  this  material. 
The  cells  become  smaller  in  size  and  eventually  exhibit  a  perfectly 
clear  basal  zone.  While  these  changes  may  be  rendered  more  con- 
spicuous by  the  use  of  pilocarpui  and  secretin,  their  complete  develop- 
ment frequently  necessitates  several  injections  of  these  drugs  until 
the  flow  of  pancreatic  juice  has  almost  ceased,  owing  to  an  exhaustion 
of  the  secretory  material.  While  the  normal  gland  possesses  a  yellow- 
ish-white color,  it  then  becomes  transparent,  soft,  and  pink  in  color. 
Methods  Employed  to  Procure  Pancreatic  Juice. — The  best  way 
in  which  pancreatic  juice  may  be  obtained,  is  to  establish  a  fistula 

1  Opie,  Diseases  of  the  Pancreas,  London,  1903,  and  Gegenbaur,  Anatomic  des 
Menschen,  Leipzig,  1899. 

2  Unters.  aus  dem  physiol.  Inst.  zu.  Heidelberg,  1882. 


934 


THE    EXTERNAL    SECRETIONS 


between  the  duct  of  Wirsung  and  the  outside.  CI.  Bernard  advocated 
the  use  of  a  lead  or  silver  cannula  which  he  inserted  in  the  orifice  of  this 
duct  and  secured  in  the  sides  of  the  abdominal  wound.  A  more  con- 
venient and  permanent  method  has  been  devised  by  Heidenhain  and 
modified  by  Pawlow.     It  makes  use  of  the  fact  that  in  the  dog  the 


Fig.  497. 


-Alveoli  of  Dog's  Pancreas,  Cells  Loaded:  Osmic  Preparation. 
Rvbasckin,  and  Ssawitsch.) 


(Babkin, 


lower  duct  is  larger  than  the  upper  and  has  a  well-defined  orifice. 
A  quadrilateral  piece  of  the  intestinal  wall  unmediately  surrounding 
this  orifice  is  resected  and  is  fastened  in  the  sides  of  the  abdominal 
wound.     The  integrity  of  the  duodenum  must  of  course  be  reestab- 


FiG.  498. — Alveoli  of  Dog's  Pancreas  after  a  Period  of  Activity  Produced  by 
Application  of  Acid  to  Mucous  Membrane  of  Duodenum.  (Babkin,  Rubasckin,  and 
iSsawitsch.) 


lished  before  the  latter  is  completely  closed.  Inasmuch  as  the  pan- 
creatic secretion  possesses  strong  proteolytic  properties,  the  external 
wound  must  be  kept  dry  and  clean,  otherwise  erosions  and  infection 
will  result.  Furthermore,  since  the  establishment  of  this  fistula 
prevents  a  large  portion  of  the  pancreatic  juice  from  entering  the 


THE    DIGESTIVE    SECRETIONS  935 

intestine,  an  animal  of  this  kind  frequently  suffers  from  indigestion 
and  metabolic  disturbances  leading  to  a  loss  of  weight  and  severe 
general  symptoms.  But  since  this  disarrangement  involves  chiefly 
the  digestion  of  the  proteins,  it  may  be  ol)viate(l  in  a  measure  by  the 
feeding  of  abundant  (juantities  of  milk  to  which  sodium  bicarbonate 
has  been  added. 

The  Character  of  the  Pancreatic  Juice. — It  is  a  clear,  watery  and 
slightly  opalescent  fluid,  i)oss(>ssing  a  specific  gravity  of  from  1.007  to 
1.009.  Moreover,  since  it  contains  considerable  amounts  of  phos- 
phates and  carbonates,  and  especially  those  of  sodium,  its  reaction  is 
strongly  alkaline.  When  its  flow  is  stimulated  by  means  of  secretin, 
about  30  to  50  c.c.  of  it  may  be  obtained  in  the  course  of  an  hour  and 
from  300  to  500  c.c.  in  a  day.     Its  composition'  is  as  follows : 

Total  solids 1 .  G  -1 .  56  per  cent. 

Total  protein 0.5    per  cent. 

Ash 1.0  -0 .  96  per  cent. 

Chlorids 0 .  28-0 .  29  per  cent. 

Total  nitrogen 0 .  73  per  cent. 

The  organic  substances  contained  in  it  are  enzymes,  a  small  amount  of 
protein  material,  and  traces  of  leucine,  tyrosine,  xanthine,  and  soaps. 
Pancreatic  juice  contains  four  enzymes  namely: 

(a)  Trypsin,  proteolytic  or  proteoclastic  in  its  nature  (Purkinje  and  Pappenheim, 
1836).  Enterokinase  converts  trypsinogen  into  trypsin.  Erepsin  is  present  some- 
times. 

(6)  Amylase;  amylopsin,  amylolytic  in  its  nature  (Valentin,  1844). 

(c)  Lipase;  steapsin,  fat-splitting,  lipolytic  or  lipoclastic  in  its  nature  (CI. 
Bernard,  1846),   and  a 

(d)  Milk-curdling  substance. 

The  Regulation  of  the  Secretion  of  Pancreatic  Juice. — It  is  com- 

mooily  held  that  the  pancreas  of  the  carnivora  secretes  intermittently, 
the  immediate  cause  of  the  secretion  being  either  nervous  or  chemical 
in  its  nature.  In  the  herbivora,  on  the  other  hand,  the  secretion  is 
constant,  a  condition  which  is  in  accord  with  the  rather  continuous 
character  of  their  digestion.  If  brought  about  in  a  reflex  way,  the 
stimuli  arise  in  the  forepart  of  the  alimentary  canal  and  are  relayed 
to  the  pancreas  by  way  of  the  vagus  nerve  which  contains  secretory 
fibers  for  this  organ.  The  fact  that  a  reflex  circuit  of  this  kind  exists 
seems  proven,  because  the  stmiulation  of  the  medulla  oblongata  is 
usually  followed  by  a  copious  flow  of  pancreatic  juice.  A  similar 
effect  may  be  obtained  by  psychic  stimuli  as  well  as  by  the  stimulation 
of  the  central  end  of  the  divided  lingual  nerve. ^  But  the  early  attempts 
of  Heidenhain  to  localize  the  secretory  fibers  of  the  pancreas  in  the 
vagus  failed  completely,  because  the  stimulation  of  this  nerve  gives 
rise  to  cardio-inhibition  and  a  fall  in  blood-pressure  which  cause  the 

1  DeZilwa,  Jour,  of  Physiol.,  xxxi,  1904,  230,  and  Wolgemuth,  Bioch.  Zeitschr., 
xxxix,  1912,  321. 

2  Pfluger's  Archiv,  x,  1875,  606. 


936  THE    EXTERNAL    SECRETIONS 

extremely  sensitive  epithelium  of  this  organ  to  cease  secreting.  Later 
on  Pawlow  conceived  the  idea  of  permitting  the  cardiac  fibers  of  the 
vagus  to  degenerate  before  attempting  to  test  the  power  of  this  nerve 
upon  the  pancreas.  In  all  these  cases,  the  stimulation  of  the  distal  end 
of  this  nerve,  3  or  4  days  after  its  division,  evoked  a  copious  flow  of 
pancreatic  juice,  but  in  spite  of  the  fact  that  the  existence  of  these 
reflex  paths  has  been  thoroughly  established,  no  definite  statements 
can  be  made  at  this  time  regarding  the  relative  importance  of  the 
nervous  and  chemical  stimuli.  At  all  events,  the  impulses  from  the 
mouth  as  well  as  those  of  psychic  origin  seem  to  play  a  less  important 
part  in  the  secretion  of  pancreatic  juice  than  in  that  of  gastric  juice. 

Inasmuch  as  a  formation  of  pancreatic  juice  also  takes  place 
after  the  pancreas  has  been  completely  isolated  from  the  central 
nervous  system,  Popielski^  came  to  the  conclusion  that  this  organ  em- 
braces a  local  nervous  mechanism  which  is  sufficient  for  its  activity. 
The  claim  was  then  made  by  Dolinsky^  and  Pawlow  that  the  active 
factor  involved  in  this  secretion  is  the  acid  of  the  gastric  juice  which 
exerts  its  peculiar  action  as  soon  as  the  chyme  is  discharged  into  the 
duodenum.  In  substantiation  of  this  contention  Popielski  proved 
later  on  that  the  injection  of  an  acid  into  a  segment  of  the  duodenum 
gives  rise  to  a  copious  flow  of  pancreatic  juice  even  after  both  vagi 
nerves  and  the  ramifications  of  the  solar  plexus  have  been  cut.  This 
fact  immediately  disposed  of  the  contention  that  the  acid  stimulates 
the  duodenal  mucosa  and  thereby  sets  up  certain  afferent  impulses 
which  are  finally  relayed  to  the  pancreas  by  way  of  the  corresponding 
fibers  of  the  vagus  system.  On  repeating  these  experiments,  Bayliss 
and  Starling^  discovered  that  a  secretion  of  pancreatic  juice  also  results 
if  the  acid  is  introduced  into  a  loop  of  duodenum  which  had  previously 
been  isolated  from  the  rest  of  the  body  by  dividing  all  its  nervous 
connections.  This  result  showed  very  clearly  that  a  chemical  stimulus 
must  be  at  work  which  affects  the  pancreatic  cells  through  the  blood 
stream.  In  further  substantiation  of  this  view  these  authors  found 
that  an  acid,  when  injected  into  the  portal  vein,  remains  without  effect, 
while  an  acid  infusion  of  the  mucous  membrane  of  the  duodenum,  when 
neutralized  and  injected  into  the  same  channel,  gives  rise  to  a  copious 
flow  of  pancreatic  juice.  These  tests  were  then  controlled  by  the  use 
of  similar  extracts  of  other  organs,  but  none  of  these  yielded  positive 
results. 

The  conclusion  to  be  derived  from  these  data  is  that  the  activity 
of  the  pancreas  is  also  under  the  control  of  a  hormone  which  originates 
in  the  mucosa  of  the  duodenum  and  upper  small  intestine.  This  agent 
is  called  secretin.  It  should  be  noted,  however,  that  it  is  not  present 
as  such  in  these  cells,  but  is  held  in  them  in  an  inactive  form  to  which 
the   name   of   pro-secretin  has  been  given.     In  consequence  of  the 

1  Centralbl.  fiir  Physiol,  x,  1896,  405,  and  xix,  1906,  801. 

2  Dissertation,  St.  Petersburgh,  1894. 
'  Jour,  of  Physiol.,  xxviii,  1902,  325. 


THE    DIGESTIVE    SECRETIONS  937 

discharge  of  the  acid  gastric  contents,  this  precursor  is  changed  into 
the  active  secretin,  which  is  then  conveyed  to  the  pancreas  in  the  blood- 
stream. This  organ  reacts  to  it  by  furnishing  an  alkaline  secretion 
which  in  turn  neutralizes  the  acid  cliynie,  thereby  setting  a  limit  to 
the  formation  of  secretin.  The  succeeding  discharge  of  chyme  gives 
rise  to  another  stimulation  by  secretin,  and  so  on  until  the  stomach  is 
empty.  The  latter  point  has  been  proved  by  Enriquez  and  Hallion^ 
in  this  way.  An  anastomosis  was  formed  between  the  arteries  and 
veins  of  two  dogs.  Canmdas  having  been  inserted  in  the  pancreatic 
ducts  of  both  animals,  one  of  them  then  received  an  inj(!ction  of  a  di- 
lute acid  into  the  duodenum.  Peculiarly  enough,  a  copious  secretion 
of  pancreatic  juice  resulted  in  both  animals.  This  experiment  proves 
very  clearly  that  secretin  is  a  true  chemical  messenger  and  is  actively 
engaged  in  the  formation  of  normal  pancreatic  juice. 

Inasmuch  as  it  has  been  noted  that  secretin  produces  at  first  a 
very  copious  flow,  which,  however,  is  soon  greatly  diminished,  and  that 
a  second  dose  of  this  agent  does  not  evoke  so  pronounced  an  effect  as 
the  first,  it  may  be  conjectured  that  this  hormone  possesses  the  func- 
tion of  exciting  the  pancreatic  secretion  in  the  shortest  possible  time. 
Accordingly,  it  may  then  be  assumed  that  it  is  the  purpose  of  the  nerv- 
ous mechanism  to  sustain  this  secretion  as  long  as  required.  This 
view  finds  support  in  the  fact  that  the  secretion  obtained  upon  stimula- 
tion of  the  vagus  nerve  is  characterized  by  a  long  latent  period,  and 
that  the  vagus-juice  is  less  watery  but  contains  a  larger  amount  of 
organic  matter  than  the  secre tin-juice.  In  analogy  with  salivary 
and  gastric  secretion,  these  differences  may  be  explained  by  assuming 
that  the  nervous  and  chemical  factors  just  mentioned  affect  different 
constituents  of  the  pancreatic  acini,  one  of  them,  possibly,  stimulating 
the  cells  of  the  acini  proper,  and  the  other  the  cells  nearer  the  excretory 
duct. 

The  chemical  nature  of  secretin  is  still  unknown.  It  is  not  a  fer- 
ment and  may  be  prepared  in  the  following  manner:  The  mucous 
membrane  of  the  duodenum  is  ground  up  with  sand  and  boiled  with 
0.4  per  cent,  hydrochloric  acid.  The  filtrate  contains  the  secretin. 
It  is  rendered  neutral  under  addition  of  sodium  hydrate.  Dale  and 
Laidlaw^  harden  the  mucosa  in  HgCl2,  boil  it,  reject  the  filtrate  and 
extract  the  residue  with  a  2  per  cent,  solution  of  acetic  acid,  containing 
1  per  cent,  of  HgCl2.  The  filtrate  is  precipitated  by  the  addition  of 
NaOH  to  the  neutral  point.  Secretin  is  stable  in  acid  solutions,  but  is 
rapidly  oxidized  in  alkaline,  and  neutral  solutions.  Its  action  is  not 
destroj'-ed  by  atropin,  although  this  agent  paralyzes  the  secretory 
mechanism  of  the  vagus.  In  this  connection,  brief  reference  should 
also  be  made  to  the  fact  that  a  flow  of  pancreatic  juice  may  be  excited 
by  means  of   pilocarpin,   Witte's  peptone,  and  curarin  (Popielski). 

1  Compt.  rend.,  Iv,  1903,  233. 

2  Proc.  Physiol.  Soc,  Jour,  of  Physiol.,  xliv,  1912. 


938 


THE    EXTERNAL    SECRETIONS 


CHAPTER  LXXX 

THE  DIGESTIVE  SECRETIONS   (CONTINUED) 
C.  BILE  AND  INTESTINAL  JUICE 

The  Liver. — The  liver  is  the  largest  gland  in  the  body,  and  is  in 
origin  a  tubular  gland  which,  in  the  course  of  its  development,  has  lost 
much  of  its  original  character.  It  is  made  up  of  rounded  masses  or 
lobules  which  measure  about  1.0  mm.  in  diameter  and  arc  composed  of 
columns  of  cells  radiating  from  a  common  center.  These  cells  possess 
a  spheroidal  shape  but  have  in  many  cases  become  polygonal  on  ac- 


FiG.  499. — Diagrammatic  Representation  of  the  Blood  Supply  of  the  Liver  Acini. 
P,  Portal  terminal;  JV,  interlobubar  veins;  CV,  central  veins  which  are  eventually 
collected  in  the  hepatic  vein;  HA,  hepatic  arteriole,  the  interlobular  capillaries  of  which 
empty  into  the  portal  terminals;  B,  biliary  capillary  which  begins  as  biliary  space  be- 
tween the  hepatic  cells, 

count  of  their  being  packed  so  closely  together.  Their  cytoplasm 
contains  a  rounded  and  centrally  placed  nucleus,  as  well  as  fatty 
particles,  and  variable  amounts  of  glycogen. 

The  blood  supply  of  this  organ  is  derived  from  two  sources,  namely  from  the 
hepatic  artery  and  the  portal  vein.  The  former  supplies  its  reticular  network, 
i.e.,  the  tissue  of  the  extra-  and  interlobular  spaces,  while  the  latter  nourishes  the 


THE    DIGESTIVE    SECRETIONS 


939 


hepatic  cells  themselves.  Evontually  the  capillaries  of  the  hepatic  artery  unite 
into  ciiaiinels  wliicli  empty  directly  into  the  terminals  of  the  portal  vein  at  the 
periphery  of  each  U)l)vile.  So  united  they  form  the  central  or  intralobular  veins, 
and  these  in  turn  the  hepatic  veins.  This  anastomosis  between  tlie  hej)atic  arterial 
and  portal  systems  accounts  for  the  fact  that  the  secretory  power  of  this  organ 
cannot  be  destroyed  by  the  ligation  of  the  aforesaid  vein,  lender  these  circum- 
stances, the  arterial  blood  finds  its  way  in  greater  quantity  into  the  portal  channels, 
thereby  compensating  in  part  for  the  loss  of  the  portal  blood.' 

The  nerve  sui)ply  of  the  liver  is  derived  from  the  celiac  ganglion  of  the  solar 
plexus.  The  individual  postganglionic  fibers  ascend  along  the  hepatic  artery 
around  which  they  form  an  intricate  i)lexus.  At  tlie  hilum  of  this  organ  they 
ramify  extensively,  foririing  here  the  so-called  hepatic  plexus.  Distally  to  this 
point  they  follow  the  br.anches  of  the  hejiatic  artery 
in  order  to  gain  the  interior  of  the  different  lobes  of 
this  organ. 

Of  special  interest  to  us  at  this  time  is 
the  fact  that  the  hepatic  cells  lie  in  direct 
contact  with  these  intralobular  capillaries, 
and  furthermore,  since  the  lining  of  these 
vessels  is  in  many  places  deficient,  the  blood 
is  brought  into  direct  communication  with 
the  contents  of  these  cells.  These  deficiencies 
account  for  the  fact  that  perfectly  intact 
red  corpuscles  may  be  found  inside  their 
cytoplasm.  Here  and  there  along  these 
vessels  we  also  note  the  so-called  stellate  cells 
of  Kupffer  which  are  large  phagocytic  bodies 
capable  of  ingesting  red  cells  and  other  solid 
particles  contained  in  the  blood.  Hence,  it 
cannot  surprise  us  to  find  that  coloring  fluids 
injected  through  the  portal  vein  may  be 
traced  directly  into  the  interior  of  these  cells 
where  they  produce  delicate  canaliculi  or 
sinusoids.  In  this  organ,  therefore,  the 
lymph  does  not  play  the  part  of  a  middle- 
man between  the  blood  and  the  cells. 

On  the  other  side  of  these  radial  rows  of  secretory  cells  are  the 
biliary  spaces  and  capillaries  which  convey  their  characteristic  se- 
cretion, the  bile,  into  the  larger  collecting  channels.  While  many  his- 
tologists  state  that  these  delicate  tubules  arise  in  secreting  vacu- 
oles within  the  cytoplasm  of  these  cells,  others  claim  that  they  begin 
as  blind  spaces  between  two  adjoining  rows  of  cells.  Farther  outward 
they  acquire  a  lining  of  columnar  epithelium  as  well  as  a  basement- 
membrane  and  fibrous  and  smooth  muscle  tissue.  In  many  animals, 
the  larger  biliary  ducts  empty  into  a  special  reservoir  which  is  known 
as  the  gall-bladder.  The  liver  is  also  plentifully  supplied  with  lym- 
phatics which  accompany  the  capillaries  of  the  portal  vein  as  well 
as  those   of  the   hepatic   artery.     These   two  systems  communicate 

1  Burton-Opitz,  Quart.  Jour,  of  Exp.  Physiol.,  iv,  1911,  93. 


Fig.  500. — Diagraai  to 
Illustrate  the  Relation  of 
THE  Portal  Terminals  (P) 
TO  the  Biliary  Capillaries 
(B).  The  Arrows  Iistdicate 
THE  Direction  of  the  Flow. 


940 


THE    EXTERNAL    SECRETIONS 


with  one  another  at  tho  periphery  of  the  lobule  as  well  as  near  the 
hilum. 

The  Function  of  the  Liver. — While  we  are  chiefly  concerned  at 
this  time  with  the  external  secretion  of  the  liver,  known  as  the  bile, 
it  should  not  be  forgotten  that  this  organ  performs  several  other  im- 
portant functions  which  may  be  briefly  summarized  as  follows: 

(a)  It  furnishes  an  internal  secretion  which  is  concerned  with  the  metabolism 
of  the  carbohydrates.  Sugar  is  deposited  in  the  hepatic  cells  in  the  form  of  gly- 
cogen, which  is  later  on  reconverted  into  sugar. 

(b)  It  forms  those  bodies  which  are  subsequently  abstracted  by  the  cells  of  the 
kidney  and  appear  in  the  urine  in  the  shape  of  urea  and  allied  substances. 

(c)  It  is  the  principal  organ  in  which  the  red  ]>lood-corpuscles  are  destroyed. 

(d)  It  plays  an  important  part  in  the  coagulation  of  the  blood,  because  it  gives 
rise  to  anti-coagulating  substances. 


Fig.  501. — LrvT:R  (  ili.^ 


CiLYi(x;EN.      (Bar/i/rth.) 


(e)  While  its  external  secretion,  the  bile,  possesses  an  important  digestive 
action  upon  the  fats,  it  is  also  a  natural  anti.septic.  an  excretory  medium,  and  a 
stimulant  of  peristaltic  activity. 

(/)   It  is  the  chief  heat-conserving  organ  in  our  body,  and  probably  also 

{g)  The  principal  formant  of  lymph. 

The  Characteristics  of  Bile. — The  quantity  of  bile  which  is  se- 
creted by  an  adult  of  medium  weight  in  a  day,  has  been  estimated  at 
500  to  1000  c.c.  It  is  not  difficult  to  obtain  it,  because  the  establish- 
ment of  a  fistula  of  the  common  duct  or  of  the  fundus  of  the  gall- 
bladder is  frequently  undertaken  to-day  for  the  relief  of  the  S5rmptoms 
following  the  obstruction  of  these  passages  by  calculi  or  by  malignant 
growths  affecting  the  pancreas  and  neighboring  orifices  of  the  duct  of 
Wirsung  and  common  bile  duct.  Bile  may  also  be  obtained  from  the 
gall-bladder  after  death,  but  if  removed  days  later,  it  may  have  lost  its 
normal  characteristics  altogether.  In  the  dog,  Pawlow  advises  to 
establish  a  biliary  fistula  by  excising  the  entire  segment  of  duodenum 
in  the  immediate  vicinity  of  the  orifice  of  the  common  duct,  and  fasten- 
ing it  to  the  edges  of  the  wound  in  the  abdominal  wall. 


THE    DIGESTrV'E    SECRETIONS  941 

Fresh  human  bile,  as  well  as  that  of  the  carnivora,  is  golden  red  in  color,  but 
changes  into  dark  green  on  exposure.  Evidently,  it  must  contain  a  number  of 
pigments  which  are  rather  unstable  and  are  altered  by  oxidation.  The  bile  of  the 
herbivora  is  greenish  in  color.  When  fresh,  it  is  very  bitter,  and  has  a  .slimy  con- 
sistency, due  to  its  content  in  mucin.  The  latter  peculiarity,  however,  is  imparted 
to  it  not  by  the  hepatic  cells  but  during  its  pa.ssage  into  the  gall-bladder.  This 
fact,  that  bile  withdrawn  from  the  hepatic  duct  and  its  tributaries  is  normally 
clear,  is  of  some  functional  importance,  Ijccause  if  it  were  not,  its  flow  might  be 
greatly  retarded.  Thus,  we  find  that  in  extreme  cases  of  biliary  catarrh  the 
larger  bile  ducts  are  frequently  blocked  by  mucous  plugs,  this  stagnation  of  the 
bile  giving  rise  to  an  absorption  of  its  pigments  and  the  complex  of  sj'^mptoms  con- 
stituting jaimdice  or  icterus.  The  viscosity  of  bile  is  1.8  times  as  great  as  that  of 
distilled  water  at37°C.'^  It  isusually  neutral  or  faintly  alkaline  to  litmus.  Per- 
fectly clear  bile  possesses  a  specific  gravity  of  1.008  to  1.010,  while  that  collected 
directly  from  the  gall-bladder  may  present  a  value  of  1.0-30  and  over. 

The  bile  of  all  animals  contains  pigments,  salts  and  cholesterol.  In  accord- 
ance with  Hammarsten.-  human  bile  obtained  from  a  fistula  of  the  hepatic  duct 
possesses  the  following  composition: 

Water 97 .  48 

Solids 2.52 

Bile  salts 0 .  93 

Taurocholate 0 .  30 

Glycocholate 0 .  63 

Fatty  acids 0 .  12 

Mucin  and  pigments 0 ,53 

Cholesterol 0  06 

Lecithin  and  fat 0  02 

Soluble  salts 0 .  SI 

Insoluble  salts 0 .  02 

The  bile  collected  directly  from  the  gall-bladder  is  more  concentrated  than 
that  withdrawn  from  the  hepatic  duct.  This  difference  is  usually  said  to  be  due  to 
an  absorption  of  its  w^ater,  but  is  caused  in  reality  by  an  ingo  of  material  from  the 
cells  lining  the  outer  biliary  passage.  In  this  way  mucin,  phosphoprotein  and  some 
cholesterol  are  added  to  the  hepatic  bile.  It  has  been  shown,  however,  that  the 
mucin  of  the  bile  of  the  ox.  dog  and  sheep  is  not  a  true  mucin,  because  it  does  not 
yield  a  carbohydrate  group  on  being  boiled  with  dilute  acid,  and  is  rather  rich  in 
phosphorus.  It  is  in  reality  a  representative  of  the  phosphoproteins  and  seems 
to  have  no  other  function  than  that  of  anointing  the  surfaces  of  the  biliarj'  chan- 
nels and  intestines.     The  mucinoid  material  in  human  bile  is  true  mucin. 

The  amount  of  bile  secreted  in  a  day  is  estimated  at  525  cc,  but  since  this  value 
has  been  obtained  from  cases  of  biliary  fistula,  it  cannot  ser\'e  as  anything  more 
than  a  general  guide. ^  Bile  is  secreted  continuously,  but  not  at  a  perfectly  uniform 
rate,  because  it  is  produced  in  smaller  amounts  during  the  early  morning  hours 
and  in  greatest  quantity  after  the  noon-day  meal. 

The  Storage  of  Bile. — In  the  majority  of  animals  the  bile  is  col- 
lected by  the  hepatic  duct  which  is  then  united  with  the  cystic  duct  to 
form  the  common  duct,  or  ductus  choledochus.  In  man,  the  latter 
opens  into  the  duodenum  about  10  to  12  cm.  below  the  pylorus,  where 
it  meets  the  pancreatic  duct  or  duct  of  Wirsung  to  form  a  papillary 
prominence.     Obviously,  this  arrangement  allows  of  a  thorough  mix- 

1  Burton-Opitz,  Bioch.  Bull.,  iii.  1914,  35. 

2  Ergebn.  der  Physiol.,  iv,  1905. 

3  Pfaff  and  Balch,  Jour,  of  Exp.  Med.,  ii,  1897,  49. 


942  THE    EXTERNAL    SECRETIONS 

ing  of  these  secretions.  The  cystic  duct  is  enlarged  peripherally  into 
a  vesicular  receptacle,  known  as  the  gall-bladder,  but  this  diverticu- 
lum is  not  present  in  all  animals,  its  place  being  taken  by  the  biliary 
ducts  themselves  which  are  then  distended  into  tubular  pouches.  A 
similar  enlargement  of  these  ducts  results  in  those  human  beings  who 
have  had  their  gall-bladder  removed  for  the  relief  of  malignant  and 
other  affections  of  this  organ.  Moreover,  it  should  be  noted  that 
those  animals  which  are  not  in  possession  of  this  storehouse  for  bile 
(horse),  show  a  rather  continuous  digestive  activity  and  require,  there- 
fore, a  more  constant  supply  of  bile. 

This  is  not  the  case  in  the  carnivora,  and  hence,  the  bile  is  stored  in 
these  animals  during  the  periods  intervening  between  the  successive 
periods  of  digestion.  Thus,  while  the  hepatic  cells  furnish  a  constant 
supply  of  bile,  the  latter  is  not  conveyed  directly  into  the  duodenum, 
but  is  diverted  through  the  cystic  duct  into  the  gall-bladder.  Its 
storage  is  made  possible  by  the  fact  that  the  orifice  of  the  common  duct 
is  guarded  by  a  transverse  band  of  smooth  muscle  tissue  which  acts 
as  a  sphincter  and  prevents  its  constant  escape.  Naturally,  the  con- 
tinuous influx  of  bile  from  the  hepatic  duct  gives  rise  to  a  gradual  disten- 
tion of  the  gall-bladder  until  a  stimulation  results  which  relaxes  this 
sphincter  and  relieves  this  organ  of  its  contents.  Thus,  we  are  really 
in  possession  of  two  separate  mechanisms,  one  for  the  secretion  and 
one  for  the  storage  and  expulsion  of  the  bile. 

According  to  Burton-Opitz,^  the  gall-bladder  is  innervated  by 
fibers  derived  from  the  celiac  ganglion  of  the  solar  plexus  which  ascend 
along  the  small  artery,  supplying  this  organ  and  neighboring  region 
of  the  liver.  Their  function  becomes  evident  if  it  is  remembered  that 
the  wall  of  this  receptacle  is  made  up  in  part  of  smooth  muscle  tissue 
which  on  contraction  lessens  its  lumen  and  subjects  its  contents  to 
a  moderate  pressure.  The  latter,  however,  rarely  exceeds  5.0  mm. 
Hg,  but  evidently,  a  greater  expelling  force  is  not  called  for,  owing 
to  the  fact  that  practically  no  resistance  need  be  overcome.  The 
pressure  at  the  orifice  of  the  common  duct  is  about  zero,  unless  raised 
momentarily  by  peristalsis,  so  that  the  only  other  prerequisite  for  a 
free  discharge  of  the  bile  is  the  relaxation  of  the  sphincter.  It  may 
rightly  be  concluded  that  the  contraction  of  the  gall-bladder  coincides 
with  the  relaxation  of  the  latter,  although  it  is  not  definitely  known 
how  this  simultaneous  action  is  brought  about.  It  has  been  estab- 
lished, however,  that  it  takes  place  shortly  after  the  entrance  of 
chyme  into  the  duodenum,  i.e.,  generally  during  the  third  hour  after 
a  meal,  but  no  clear  picture  can  be  drawn  of  the  mechanism  involved 
in  this  process.  For  the  present,  therefore,  it  must  be  regarded  as  a 
reflex  evoked  in  the  duodenum,  the  local  nerve  paths  of  which  are 
contained  in  the  plexus  celiacus,  plexus  hepaticus  and  plexus  gastro- 
duodenahs.     Preganglionically,  the  motor  fibers  of  the  gall-bladder 

1  Am.  Jour,  of  Physiol.,  xlv,  1917,  62. 


THE    DIGESTIVE    SECRETIONS  943 

have  been  dotected  in  the  vagus  and  greater  splanchnic  nerves,  but 
no  very  convincing  data  have  been  obtained.^ 

The  Formation  of  Bile. — It  has  been  stated  above  that  the  bile 
is  secreted  continuously  but  not  at  a  uniform  rate.  Naturally,  this 
variation  is  dependent  upon  intermittent  stimuli,  such  as  result 
whenever  the  stomach  ejects  its  contents  into  the  duodenum.  This 
fact  suffices  to  show  that  the  hepatic  cells  are  under  the  control  of  a 
mechanism  which  regulates  their  activity.  The  latter  may  be  either 
nervous  or  chemical  in  its  nature.  Thus,  it  may  be  assumed  that  the 
liver  is  in  possession  of  secretory  fibers  which  arise  in  the  celiac 
ganglion  and  reach  this  organ  by  wa}^  of  the  hepatic  plexus.  But 
since  a  reflex  contraction  of  the  gall-bladder  and  a  more  copious 
flow  of  bile  may  also  be  evoked  by  the  introduction  of  an  acid  into  the 
duodenum,  and  since  these  effects  may  also  be  obtained  after  the  liver 
has  been  isolated  from  the  central  nervous  system  by  the  division  of 
its  nerves,  it  has  been  concluded  that  the  secretion  of  bile  is  also  regu- 
lated by  a  specific  hormone.  Starling  recognizes  in  this  chemical 
stimulant  the  secretin  of  the  duodenal  mucosa,  his  claim  being  based 
upon  the  fact  that  the  injection  of  this  agent  into  the  blood  stream 
evokes  a  copious  flow  of  bile.  We  shall  see  later  on  that  secretin 
also  excites  a  secretion  of  intestinal  juice,  and  hence,  it  may  be  held 
that  it  serves  as  the  initial  stimulus  for  three  of  the  principal  digestive 
fluids. 

Inasmuch  as  the  hepatic  cells  derive  the  material  from  which  they 
form  the  bile  from  the  portal  vein,  their  activities  must  be  adjusted 
to  a  very  low  secretory  pressure.  It  has  been  shown  by  Burton-Opitz^ 
that  the  blood  arrives  in  the  tributaries  of  the  portal  system  of  the 
dog  under  a  pressure  of  about  12  mm.  Hg  and  enters  the  hilum  of  the 
liver  under  a  pressure  of  9  mm.  Hg.  In  the  cat,  the  pressure  encoun- 
tered at  this  point  amounts  to  only  7  mm.  Hg.  Now,  since  the  pres- 
sure in  the  inferior  vena  cava  opposite  the  orifices  of  the  hepatic  veins 
is  practically  zero,  a  pressure  of  about  9  mm.  Hg  must  suffice  to  drive 
the  blood  through  the  portal  terminals.  This  is  the  pressure  under 
which  the  hepatic  cells  perform  their  secretory  function.  The  blood 
of  the  hepatic  artery,  on  the  other  hand,  arrives  at  the  liver,  say, 
under  a  pressure  of  100  mm.  Hg,  which  is  used  up  very  largely  in  its 
task  of  overcoming  the  resistance  in  the  interstitial  capillaries.  Both 
types  of  blood  then  traverse  the  intralobular  veins,  that  of  the  portal 
vein  furnishing  the  secretory  material,  and  that  of  the  hepatic  artery 
the  oxygen. 

If  the  general  blood  pressure  is  reduced,  the  quantity  of  bile  se- 
creted is  diminished,  while  its  percentage  of  solids  is  increased.  This 
same  effect  may  be  produced  by  the  excitation  of  the  vasoconstrictor 
fibers  of  the  liver  or  by  the  ligation  of  several  branches  of  the  portal 

1  Bainbridge  and  Dale,  Jour,  of  Physiol.,  xxxiii,  1905,  138;  Doyon.  Archives  de 
Physiol.,  1891,  and  Free.se,  Bull.  Johns  Hopkins  Univ.  Hosp.,  xvi,  1905. 
^  Quart.  Jour,  of  Exp.  Physiol.,  vii,  1913,  57. 


944  THE    EXTERNAL    SECRETIONS 

vein.  These  facts  clearly  show  that  the  secretion  of  bile  is  closely 
dependent  upon  a  proper  secretory  pressure.  It  should  be  noted, 
however,  that  the  formation  of  bile  takes  place  in  accordance  with 
the  same  principles  as  the  formation  of  other  secretions;  i.e.,  it  is  not 
due  to  filtration  alone  but  also  to  osmosis,  diffusion,  and  a  certain 
vital  activity  on  the  part  of  the  hepatic  cells.  To  prove  this  point, 
it  may  be  shown  that  these  cells  are  able  to  secrete  against  a  higher 
pressure  than  the  portal  blood  pressure.  Thus,  if  a  cannula  is  inserted 
in  the  common  duct  which  in  turn  is  connected  with  a  narrow  vertical 
glass  tube,  the  bile  will  rise  in  this  tube  until  its  height  equals  a  pres- 
sure considerably  above  that  prevailing  in  the  portal  vein  at  the  hilum 
of  the  Hver.  How  rapidly  this  level  will  be  reached  differs  with  the 
general  condition  of  the  animal.  In  a  I'obust  cat  under  ether,  prob- 
ably 30  to  60  minutes  will  be  required  before  the  pressure  in  the  com- 
mon duct  will  have  risen  to  15  mm.  Hg,  which  equals  twice  the  pres- 
sure ordinarily  encountered  in  the  portal  vein  of  this  animal.  In  the 
dog,  a  pressure  of  15  to  20  mm.  Hg  may  be  established  before  the 
secretion  of  bile  ceases.  Clearly,  since  the  hepatic  cells  are  capable 
of  secreting  against  a  pressure  higher  than  that  under  which  they 
obtain  their  material,  filtration  cannot  be  the  onh'  factor  concerned 
in  this  process. 

A  very  good  proof  of  the  secretory  power  of  the  hepatic  cells  is 
also  furnished  by  the  factthat  the  constituents  of  the  bile  are  not  brought 
to  the  hver  in  their  complete  form  but  are  formed  here  from  their 
precursors.  Lastly,  it  is  possible  to  vary  the  secretion  of  bile  by  chem- 
ical agents  which  act  in  the  manner  of  secretogogues,  and  stimulate 
the  cells  direct^.  These  bile-driving  substances  are  known  as  chola- 
gogues.  "Wliile  aloes,  calomel,  peptone  and  salic^'lates  may  be  used 
for  this  purpose,  the  most  powerful  agent  is  the  bile  itself.  Scliiff, 
however,  has  shown  that  if  the  bile  is  administered  by  the  mouth  or 
through  an  intestinal  fistula,  a  considerable  portion  of  it  is  absorbed. 
Thus,  at  least  a  part  of  the  cholagogic  action  of  the  constituents  of  bile 
may  be  due  to  the  fact  that  the  material  absorbed  is  again  made  use 
of  in  the  formation  of  new  bile.  To  prove  this  point  Wertheimer^ 
injected  sheep's  bile  into  the  mesenteric  vein  of  a  dog  and  was  able  to 
demonstrate  the  presence  of  cholohematin  in  the  bile  of  this  animal. 
This  body  occurs  normally  onh-  in  the  bile  of  the  sheep. 

Icterus.  Cholemia.  Resorption  of  Bile: — While  it  cannot  be 
doubted  that  the  hepatic  cells  are  capable  of  secreting  against  a  higher 
pressure  than  that  prevaihng  in  the  portal  vein,  this  process  cannot 
be  continued  indefinitely.  The  upper  limit  having  been  reached, 
the  secretion  ceases  and  some  of  the  constituents  of  the  stagnated 
bile  pass  over  into  the  circulation.  This  resorption  gives  rise  to  the 
condition  of  icterus  or  jaundice,  which  is  characterized  by  a  deposition 
of  the  biliary  pigments  in  the  tissues  of  the  bod}',  causing  a   j'ellow 

1  Archive  de  physiol.  norm,  et  path.,  1892,  577;  Stadehnan,  Zeitschr.  fiir  Biol., 
xvi,  1897,  1;  Whipple  and  Hooper,  Am.  Jour,  of  Physiol.,  xl,  1916,  349. 


THE    DIGESTIVE    SECRETIONS  945 

discoloration  of  the  sclera,  conjunctiva  and  mucous  surfaces.  This 
pignu'iitous  material  also  appeai.s  in  the  urine  and  finally  gives  rise 
to  a  reduction  in  the  frequency  of  the  heart  and  respiration  and  a 
general  bodily  and  mental  fatigue. 

A  condition  of  this  kind  may  arise  in  consequence  of  a  catarrhal  inflammation 
of  the  larger  biliary  passages  and  the  formation  of  mucous  plugs,  or  in  consequence 
of  the  escape  of  a  calculus  from  the  gall-bladder  which  later  on  becomes  firmly 
wedged  in  between  this  organ  and  the  duodenum.  Under  these  circumstances 
the  feces  assume  a  grayish  color  and  the  consistency  of  clay,  owing  to  the  absence 
of  bile  and  the  residtant  accumulation  of  much  undigested  fat.  Defecation  be- 
comes infrequent  and  labored,  owing  to  the  loss  of  the  tonicity  of  the  intestinal 
musculature  and  the  solidity  of  the  fecal  material.  Jaimdice  may  also  be 
incited  by  the  administration  of  poisons  which,  however,  do  not  produce  an  actual 
obstruction  of  the  larger  biliary  passages.  The  cause  of  this  non-obstructive  type 
of  icterus  is  more  difficult  to  explain,  unless  it  is  held  that  the  poison  gives  rise  to 
an  erosion  and  obliteration  of  the  intralobular  channels.  This  result  is  quite  com- 
mon in  all  conditions  producing  an  excessiv^e  destruction  of  red  cells.  It  is  generally 
believed  that  this  resorption  of  bile  takes  place  through  the  lymphatics  and  not 
through  the  blood-capillaries,^  because  the  ligation  of  the  common  duct  does  not 
give  rise  to  jaundice  if  the  thoracic  duct  is  obstructed  at  the  same  time. 

Extirpation  of  the  Liver. — It  has  previously  been  shown  that  the 
secretion  of  bile  is  dependent  upon  filtration,  diffusion  and  osmosis, 
and  a  vital  activity  of  the  cells.  Attention  has  also  been  called  to  the 
fact  that  bile  is  secreted  continuously  but  not  at  a  uniform  rate,  be- 
cause different  stimulations  result  from  time  to  time  which  vary  its 
formation.  Chief  among  these  is  the  chyme  which,  upon  its  ejection 
into  the  duodenum,  evokes  a  local  reflex  and  liberates  the  hormone 
secretin.  By  this  means  the  increased  activity  of  the  hepatic  cells  is 
made  to  coincide  precisely  with  the  evacuation  of  the  gall-bladder,  so 
that  both  processes  occur  at  about  the  third  hour  of  digestion  and 
synchronously  with  the  outpouring  of  the  pancreatic  juice.  In  this 
connection  it  is  of  interest  to  note  that  the  digestive  products  of  the 
proteins  and  fats  evoke  a  much  more  copious  flow  of  bile  than  the 
carbohydrates.  It  may  also  be  increased  by  a  large  intake  of  water, 
and  diminished  by  hunger  and  emotions. 

The  hgation  of  the  portal  vein  does  not  stop  this  secretion  alto- 
gether, because  the  hepatic  artery  is  able  for  a  time  to  compensate 
for  the  loss  of  the  portal  blood.  But  this  compensation  soon  proves 
wholly  inadequate  to  sustain  life  and  the  animal  succumbs  to  a  vas- 
cular depression  brought  about  by  the  engorgement  of  the  portal 
circuit.  2  Much  better  results  may  be  obtained  if  an  artificial  com- 
munication is  first  established  between  the  portal  vein  and  the  inferior 

1  Mendel  and  Underbill,  Am.  Jour,  of  Physiol.,  xiv,  1905,  252,  and  Eppinger, 
Ziegler's  Beitr.,  xxxi,  1903,  230. 

2  The  ligation  of  the  portal  vein  distally  to  the  orifice  of  the  pancreatic  vein 
does  not  prove  fatal,  because  the  blood  of  the  mesenteric  veins  then  flows  into  the 
splenic  vein,  whence  it  reaches  the  gastric  veins  and  the  hilum  of  the  liver  by  way 
of  the  pancreatic  veins.  This  reversal  of  the  splenic  blood  stream  is  made  possible 
by  the  enlargement  of  the  small  veins  upon  the  pylorus,  ordinarily  connecting  the 
pancreatic  vein  with  the  gastric  veins. 

60 


946  THE    EXTERNAL    SECRETIONS 

vena  cava  (Eck  fistula)  by  uniting  the  edges  of  a  longitudinal  incision 
in  the  wall  of  the  former  blood-vessel  with  those  of  a  similar  opening 
in  the  latter.^  In  birds,  a  communication  of  this  kind  is  normally- 
present  in  the  form  of  a  small  channel  which  connects  the  capillary 
expanse  of  the  renal-portal  system  with  the  portal  vein.  Consequently, 
the  portal  vein  of  these  animals  may  be  ligated  without  causing 
serious  disturbances.  The  total  removal  of  the  liver,  however,  even- 
tually proves  fatal,  on  account  of  the  loss  of  the  necessary  amounts  of 
bile  and  other  products  of  the  hepatic  cells,  such  as  the  precursors 
of  uric  acid,  salts  and  pigments.  The  latter  are  even  more  important 
than  the  former  in  spite  of  the  fact  that  the  loss  of  bile  gives  rise  to 
serious  digestive  disturbances.  The  method  of  partial  and  total  ex- 
tirpation of  the  liver  has  been  made  use  of  more  particularly  as  a 
means  of  showing  that  the  special  constituents  of  the  bile  are  actually 
synthetized  in  this  organ  and  are  not  brought  to  it  in  their  complete 
form.  Naturally,  the  raw  material  from  which  these  substances  ai'e 
derived  is  the  blood  pigment,  hemoglobin.  This  can  be  proved  either 
by  injecting  this  substance  into  the  blood  stream  or  by  inciting  a  greater 
destruction  of  the  red  cells  by  means  of  hemolytic  agents.  It  will  be 
found  that  the  amount  of  the  corresponding  constituents  of  bile  is 
directly  proportional  to  the  destruction  of  these  cells.  A  similar 
reduction  of  the  hemoglobin  takes  place  in  those  tissues  which  have 
been  the  seat  of  an  extravasation.  As  the  hematin  of  these  extra- 
vasates  is  slowly  converted  into  bodies  similar  to  the  bile-pigments, 
the  tissues  so  affected  assume  different  shades  of  purple,  blue  and 
yellow. 

It  has  already  been  pointed  out  that  the  life  of  the  red  blood  cor- 
puscles is  limited  and  that  the  "senile"  ones  are  gradually  removed 
from  the  circulation  while  they  traverse  the  capillaries  of  the  liver  and 
spleen.  But  their  destruction  cannot  be  accompanied  by  a  discharge 
of  their  hemoglobin  into  the  blood  stream,  because  this  substance  is 
taken  up  by  the  different  phagocytic  cells,  such  as  the  cells  of  Kupffer 
lining  the  intrahepatic  spaces.  These  cells  also  possess  the  power  of 
engulfing  and  destroying  the  red  cells  in  their  entirety,  a  process  which 
may  be  more  directly  studied  in  the  amphibia,  because  the  red  cells 
of  these  animals  contain  a  sharply  differentiated  nucleus.  In  these 
animals,  any  excessive  destruction  of  their  red  cells  is  invariably 
followed  by  an  accumulation  of  a  bright  green  pigment  within 
these  phagocytes,  which  presents  all  the  characteristics  of  biliverdin. 
A  similar  deposition  of  this  material  takes  place  in  the  neighboring 
endothelial  lining  cells  as  well  as  in  the  hepatic  cells  themselves.  These 
accumulations  of  pigment  may  be  rendered  more  conspicuous  by 
staining  them  with  potassium  ferrocyanid  which  colors  them  blue, 

1  Nencki,  Pawlow  and  Zaleski,  Archiv  fiir  Exp.  Path.,  xxxvii,  1896,  26;  Carrel 
and  Guthrie,  Compt.  rend.,  1906,  and  Bernheim  and  Voegtlin,  Jour,  of  Pharm. 
and  Exp.  Ther.,  i,  1909,  463. 


THE    DIGESTIVE    SECRETIONS  947 

or  with  ammonium   sulpiiid  wliicii,  owing  to  their  content   in  iron, 
colors  them  dark  brown. 

Special  Constituents  of  Bile. — The  bile  contains  the  sodium 
salts  of  complex  aniino-acids,  such  as  glycocholic,  taurocholic,  glyco- 
choleic  and  taurocholeic.  The  relative  proportion  of  these  salts  differs 
in  different  animals,  glycocholic  acid  being  more  al)undant  in  the  bile 
of  man  and  herbivora,  and  taurocholic  acid  in  that  of  the  carnivora. 
They  are  formed  as  soon  as  the  liver  attains  its  full  functional  develop- 
ment and  do  not  arise  elsewhere  in  the  body.  Their  detection  is 
made  possible  by  means  of  Pettenkofer's  reaction,  which  consists  in 
adding  a  few  drops  of  a  10  per  cent,  solution  of  cane-sugar  and  con- 
centrated sulphuric  acid  to  the  suspected  liquid.  If  the  latter  con- 
tains bile  salts,  a  violet  ring  develops  at  its  point  of  contact  with  the 
reagent.  This  coloration  is  due  to  the  formation  of  an  aldehyde-like 
furfurol  by  the  acid  from  the  sugar,  and  the  condensation  of  this  prod- 
uct with  the  bile  salts. 

The  bile  salts  may  be  prepared  by  mixing  fresh  bile  with  about  1  per  cent,  by 
weight  of  animal  charcoal.  This  liquid  is  evaporated  to  dryness  on  the  water  bath, 
and  the  residue  powdered  and  extracted  with  water  and  filtered.  The  filtrate  is 
acidified,  but  contains,  in  addition  to  the  bile  salts,  also  some  cholesterol,  mucin, 
phosphatides  and  inorganic  salts.  Crystallized  bile'  is  prepared  in  the  same  way, 
excepting  that  the  dried  mixture  of  charcoal  and  bile  is  extracted  with  boiling  ab- 
solute alcohol.  Since  the  bile  salts  are  very  soluble  in  alcohol,  they  are  separated 
out  immediately,  leaving  the  other  constituents  behind.  The  alcohol  is  filtered 
and  mixed  with  absolute  etheruntil  a  precipitate  isformed.  On  cooling,  the  bile 
salts  crystallize  out,  but  since  they  absorb  water  very  readily,  they  should  be  kept 
in  a  desiccator.  The  glycocholic  acid  may  be  hydrolyzed  by  dilute  acids  and  alkalies 
and  split  into  glycerin  or  amino-acetic  acid  and  cholic  acid. 

C26H43NO6  +  H.O  =  CH2(NH,)COOH  +  C24H40O8 

(Glycocholic  acid)  (Glycine)  (Cholic  acid) 

In  the  same  way  taurocholic  acid  may  be  split  into  taurine,  or  amino-ethyl-sul- 
phonic  acid  and  cholic  acid. 

C,6H45N07S  +  H2O  =  CH3CH(NH2)S020H  +  C.24H40O5 

(Taurocholic  acid)  (Taurine)  (Cholic  acid) 

It  will  be  shown  later  on  that  the  bile  salts  stimulate  peristalsis  and  serve  as 
a  vehicle  for  the  digestion  of  the  fats.  Their  function  having  been  completed,  a 
portion  of  them  is  destroyed  through  the  influence  of  the  intestinal  microorganisms, 
while  another  portion  is  again  absorbed  and  returned  to  the  liver  bj^  way  of  the 
portal  blood  stream.  The  hepatic  cells  rebuild  this  material  into  new  bile  salts, 
thereby  greatly  reducing  their  work  in  synthetizing  these  salts.  A  similar  "cir- 
culation of  the  bile"  between  the  intestine  and  the  liver  is  had  in  the  case  of  some 
of  the  derivatives  of  the  pigmentous  material  of  the  bile. 

Cholic  or  cholalic  acid  is  a  white,  crystalline  and  very  bitter  substance  which 
is  almost  insoluble  in  water,  but  soluble  in  alcohol.  On  addition  of  water  it  crys- 
tallizes from  the  latter  in  rhombic  pyramids  and  tetrahedrons.  It  is  closely  allied 
to  cholesterol  and  may  be  derived  from  this  substance. 

Cholesterol  has  been  found  in  the  bile  of  almost  all  animals,  but  is  not  present  in 
considerable  amounts  in  himian  bile  (1.6  in  1000  parts).  Since  it  is  insoluble  in 
water  and  solutions  of  salts,  it  must  seem  peculiar  that  it  is  dissolved  by  the  bile 
and  may  be  present  here  in  even  greater  amounts  than  normal.  This  excessive 
solvent  action  of  bile  is  due  to  its  content  in  bile  salts  and  more  particularly  to  the 

1  Platner,  Ann.  der  Chemie  und  Pharmazie,  li,  1844,  105. 


948  THE  EXTERNAL  SECRETIONS 

cholic  acid  radicle  of  the  latter,  which  unites  in  some  way  with  the  cholesterol  and 
keeps  it  in  solution.  Little  is  known  regarding  the  origin  of  this  substance.  It 
may  be  derived  from  the  food  or  from  the  cholesterol  of  the  destroyed  red  blood 
corpuscles.  Regarding  its  i)lace  of  origin,  Naunyn  makes  the  assertion  that  it  is 
eliminated  chiefly  by  the  lining  cells  of  the  gall-bladder,  this  statement  being  based 
upon  the  fact  that  the  bileof  the  latter  contains  a  larger  amount  of  cholesterolthan 
that  of  the  hepatic  duct.  But  since  the  relative  richness  of  the  bladder-bile  in 
this  substance  may  be  due  to  the  fact  that  the  cholesterol  here  secreted  is  not  so 
easily  converted  into  bile  salts,  the  preceding  deduction  may  not  be  correct.  A 
disturbance  of  tliese  oxidations  in  consequence  of  traumatism  and  inflammation 
of  the  wall  of  the  bladder,  or  in  consequence  of  general  metabolic  disorders  (meno- 
pause), frequently  leads  to  the  formation  of  gall-stones  which  may  at  times  occupy 
every  recess  of  the  bladder  and  also  find  their  way  into  the  large  biliary  channels. 
The  constant  irritation  set  up  by  these  concretions  tends  to  excite  contractions 
of  the  bladder  which  in  the  course  of  time  mold  these  masses  into  many-sided 
fragments  possessing  sharp  points  and  sides.  As  has  just  been  stated,  the  chief 
constituent  of  these  concretions  is  cholesterol  (20  to  90  per  cent.)  to  which  some 
desquamated  epithelium  has  been  added. ^ 

The  phosphoUpijts  of  bile  present  themselves  principally  in  the  form  of  lecithin. 
Practically  nothing  is  known  regarding  their  origin  and  function.  In  human  bile 
the  lecithin,  obtained  from  the  alcohol-soluble  material,  amounts  to  1.7  per  cent., 
but  varies  considerably  in  accordance  with  the  character  of  the  food  ingested. 
This  fact  might  lead  us  to  suspect  that  it  is  derived  from  the  constituents  of  the 
diet,  but  it  may  also  be  true  that  it  originates  from  the  destroyed  red  blood  cor- 
puscles. 

The  peculiar  color  of  the  bile  of  the  carnivora  is  due  to  certain  pigments  of  which 
bilirubin  is  the  most  important.  This  substance  is  unstable  and  is  easily  oxidized 
into  a  green  pigment,  known  as  biliverdin,  which  in  turn  gives  rise  to  a  whole  series 
of  bodies,  such  as  the  blue  biUcyanin.  On  further  reduction  it  is  converted  into 
urobilin,  one  of  the  coloring  materials  of  urine.  In  the  herbivora  the  chief  pigment 
is  biliverdin,  but  it  seems  that  the  aforesaid  pigments  are  interchangeable.  Bili- 
rubin (CsjHsoXoOs)  is  an  iron-free  compound  and  is  derived  from  the  hemoglobin 
of  the  red  corpuscles.  Consequently,  its  formation  must  be  dependent  upon  the 
rate  of  destruction  of  these  cells.  Since  the  bile  contains  only  a  trace  of  iron,  it  may 
be  surmised  that  this  element  is  stored  in  the  liver  cells  to  be  made  use  of  sub- 
sequently in  the  formation  of  new  hemoglobin.  Bilirubin  is  prepared  from 
powdered  red  gall-stones  by  dissolving  the  chalk  with  hydrochloric  acid  and  extract- 
ing the  residue  successively  with  chloroform.  The  pigment  crystalhzes  from  this 
solution  in  beautiful  rhombic  tables  or  prisms.  Biliverdin  (C32HsfiN408)  is  an 
amorphous  iron-free  body.  It  may  be  formed  from  bilirubin  by  oxidation  and  may 
be  reconverted  into  this  pigment  by  putrefaction  or  by  the  addition  of  ammonium 
sulphid.  By  reduction  with  sodium  amalgam  it  is  changed  into  hydrobilirubin, 
a  substance  identical  with  stereobilin.  Similar  reductions  go  on  when  the  bile 
pigments  reach  the  intestine,  so  that  they  are  not  recognizable  as  such  in  the  feces 
or  urine.  The  most  important  derivative  of  bilirubin  is  sterconibin  or  urobiUn. 
To  this  body  is  due  the  brown  color  of  the  feces.  In  urine  it  appears  as  urobiligen, 
a  colorless  substance  which  is  changed  into  urobilin  under  the  influence  of  the  oxy- 
gen of  the  air.  ^\Tien  the  bile  is  prevented  from  entering  the  intestine,  the  urine 
does  not  contain  this  substance. 

The  Intestinal  Glands. — The  mucous  membrane  of  the  small 
intestine  contains  numerous  goblet  cells,  similar  in  structure  to  those 
previously  noted  in  the  mucosa  of  the  stomach.  Their  function  is  to 
discharge  mucus  which  serves  to  lubricate  the  surfaces  of  the  intestine 

1  Kramer,  Jour,  of  Exp.  Med.,  ix,  1907;  Lichtwitz,  Arch.  klin.  Med.,  xcii,1907, 
100,  and  Bacmeister,  Miinch.  med.  Wochenschr.,1908. 


THE    DIGESTIVE    SECRETIONS 


949 


and  to  render  the  feces  more  slippery.  In  between  the  different  viUi, 
however,  the  mucous  membrane  is  pervaded  by  simple  tubular  glands 
which  arc  known  as  the  crypts  of  Lieberkiihn.  The  latter  are  hned 
throughout  by  a  single  row  of  columnar  epithelium,  among  which  are 
found  a  few  goblet  cells.  In  the  crypts  of  the  large  intestine,  on  the 
other  hand,  these  mucous  cells  increase  in  number  and  finally  displace 
the  secretory  cells  altogether.  This  structural  change  is  in  complete 
harmony  with  the  fact  that  the  crypts  of  the  large  intestine  form  only 
mucus  for  purposes  of  lulirication. 

The  Secretion  of  the  Intestinal  Juice  or  Succus  Entericus. — Un- 
adulterated intestinal  juice  may  be  obtained  by  means  of  a  fistula. 
The  method  of  Thiery  (18(>4)  consists 
in  isolating  a  loop  of  intestine  by  two 
transverse  cuts  made  at  some  distance 
from  one  another.^  The  intervening 
segment  is  left  in  connection  with  its 
normal  blood  and  nerve  supply  and 
is  brought  close  to  the  abdominal 
wall.  Its  upper  end  is  then  closed 
by  sutures,  while  its  lower  end  is 
anchored  to  the  sides  of  the  wound 
in  the  abdominal  wall.  The  contin- 
uity of  the  intestine  from  which  this 
loop  has  been  obtained  is  restored 
by  an  end-to-end  anastomosis.     Vella 

of  the 

of   the 


advises  to  fasten  both  ends 
isolated  loop  to  the  edges 
wound  in  the  abdominal  wall. 


Fig.  502. — Diagram  to  Illustrate 
THE  Relation  Between-  the  Villi  and 
THE  Crypts  of  Lieberkuhn. 

V,  Villus;  G,  goblet  cells  secreting 
mucus;  C,  crypt  of  Lieberkuhn;  L, 
lacteal. 


The  juice  obtained  from  such  isolated 
segments  of  the  small  intestine  is  light  yellow 
in  color,  opalescent,  very  watery  and  strongly 
alkaline  in  reaction.  It  possesses  a  specific 
gravity  of  1.010,  and  contains  1.07  per  cent, 
of  solids,  of  which  0.2  per  cent,  are  appor- 
tioned to  Xa-jCOs  and  0.58  per  cent,  to 
NaCl.     Its  small  content  in  proteins  is  made 

up  of  serum  albumin  and  serum  globulin.  Its  quantity  is  considerable,  a  short 
segment  of  intestine  furnishing  as  much  as  200  c.c.  of  juice  in  the  course  of  a 
day.  2  One  of  the  commonest  means  used  to  excite  its  flow  is  to  introduce  a  rubber 
tube  through  the  fistulous  opening,  but  Pawlow  states  that  the  character  of  the 
juice  is  then  somewhat  different  from  that  obtained  without  this  mechanical 
stimulation,  one  of  the  points  of  difference  being  that  it  contains  no  enterokinase. 
Its  flow  may  also  be  increased  by  dividing  the  mesenteric  plexus,'  or  by  produc- 
ing hydremic  plethora. 

In  the  former  case,  a  copious  secretion  sets  in  very  shortly  after  the  section  of 
these  nerve  fibers  and  continues  for  about  24  hours.  Clear  at  first,  the  fluid  soon 
becomes  cloudy  and  milky  until  it  assumes  the  consistency  of  a  thick  broth.     WTiile 

1  Pawlow,    Chirurgie  des   Verdauungskanals,  Ergebn.  der  Physiol.,  i,  1902. 

2  Frouin,  Compt.  rend.,  Ivi,  1904,  461. 

3  Mendel,  Pfliiger's  Archiv,  Ixiii,  1896,  425. 


950  THE    EXTERNAL    SECRETIONS 

we  might  regard  this  liquid  as  a  true  secretory  j^roduct  of  the  glands  of  Lieberkiihn, 
it  should  not  be  forgotten  that  a  considerable  portion  of  it  may  be  produced  by 
transudation  following  the  relaxation  of  the  intestinal  blood-vessels.  In  general, 
this  pnenomenon  may  be  compared  to  the  paral^^tic  secretion  of  saliva. 

The  intestinal  juice  contains  several  ferments,  two  of  which  are  proteolytic  in 
their  action.  Of  these  enferokinase  has  already  been  mentioned  in  connection  with 
the  activities  of  Brunner's  glands.  The  other,  which  is  known  as  erepsin,  is  present 
in  this  juice  as  well  as  in  almost  all  tissues  of  the  body.  Among  the  ferments 
affecting  the  carbohydrates,  may  be  mentioned  invertase  which  transforms  sugar 
into  glucose  and  levulose  or  fructose,  and  maltase  which  changes  maltose  into 
glucose.  1  Excepting  enterokinase,  these  ferments  have  also  been  regarded  as  intra- 
cellular agents  and  not  as  constituents  of  the  juice  itself.  In  this  form,  they  should 
exert  their  action  upon  the  different  foodstuffs  while  the  latter  traverse  the  epithe- 
lial cells  on  their  way  to  the  channels  of  absorption.  This  contention  is  founded 
upon  the  fact  that  the  liquid  obtained  by  extracting  the  intestinal  mucosa  forms 
a  more  powerful  digestive  medium  than  the  intestinal  juice  itself.  In  all  previous 
instances,  we  have  observed  that  a  simple  extract  of  the  mucosa  is  inactive,  but  may 
be  activated  very  readily  by  giving  to  it  the  reaction  which  it  necessitates.  Entero- 
kinase, on  the  otiisr  hand,  is  not  contained  as  such  in  the  epithelial  lining  cells  but 
only  in  the  form  of  a  precursor  which  assumes  its  activity  immediately  after  its 
discharge  into  the  general  juice  of  the  intestine. 

The  regulation  of  this  secretion  is  effected  by  a  nervous  as  well 
as  a  chemical  factor.  The  former  is  mediated  by  the  peripheral 
expanse  of  the  autonomic  system  of  this  particular  region  of  the  body, 
which  presents  itself  in  the  form  of  the  plexuses  of  ]\Ieissner  and  Auer- 
bach.  These  networks  of  sympathetic  fibers  are  situated  beneath  the 
submucosa.  The  fact  that  reflexes  play  a  part  in  the  secretion  of 
intestinal  juice  may  be  gathered  from  the  close  dependency  of  this 
process  upon  extraneous  stimuli. ^  Thus,  a  dog  which  had  not  been 
fed  for  a  period  of  about  24  hours  showed  a  flow  within  15  minutes 
after  the  ingestion  of  food;  moreover,  this  flow  reached  its  maximum 
in  about  3  hours,  i.e.,  at  a  time  when  the  pancreatic  juice  was  produced 
most  copiously.  But  since  the  intestinal  secretion  does  not  cease 
after  the  intestine  has  been  completely  isolated  from  the  central 
nervous  system  by  the  division  of  the  vagi  and  sympathetic  nerves, 
some  other  agent  must  be  at  work,  presumabl}^  in  the  form  of  a  se- 
cretogogue. Although  the  nature  and  place  of  origin  of  this  hormone 
have  not  been  made  out  with  any  degree  of  definiteness,  Delezenne 
and  Frouin^  have  proved  that  the  injection  of  secretin  into  the  blood 
stream  of  animals  provided  with  an  intestinal  fistula  gives  rise  to 
a  copious  flow  of  this  juice.  It  seems,  therefore,  that  this  chemical 
messenger  acts  simultaneously  upon  three  organs,  namely,  upon  the 
pancreas,  hver  and  glands  of  Lieberkiihn,  insuring  therebj'^  a  concerted 
action  of  these  secretions  upon  the  acid  gastric  ch3mie.  But  certain 
evidence  is  also  at  hand  to  show  that  some  other  chemical  agent  is 
liberated  in  the  lower  part  of  the  small  intestine,  synchronously'  with 
the  intestinal  juice.     The  nature  of  this  hormone  is  not  known. 

1  Weinland,  Zeitschr.  fiir  bid.  Chemie,  xlvii,  1905,  279. 
-  Bayliss  and  Starling,  Ergebn.  der  Physiol.,  1906. 
3  Proc.  Soc.  Biol.,  Ivi,  1906,  319. 


SECTION  XXV 
THE  INTERNAL  SECRETIONS 


CHAPTER  LXXXI 


THE  THYROID  AND  PARATHYROID  BODIES.    THE  THYMUS, 
LIVER,  AND  PANCREAS 

General  Discussion. ' — The  bcginnin^j;  of  the  scientific  studj'  of  the 
ductless  glands  dates  from  1849,  when  Berthold^  showed  that  the  tes- 
ticles produce  an  internal  agent  which  is  transferred  by  them  directly 
into  the  blood-stream.  He  proved  his  point  by  removing  these  organs 
from  cocks  and  grafting  them  upon  some  other  part  of  the  body. 
Peculiarly  enough,  these  animals  "remained  male  in  regard  to  voice, 
reproductive  instinct,  fighting  spirit,  and  growth  of  comb  and  wattles.'* 
In  1855,  Claude  Bernard^  gave  a  more  elaborate  presentation  of  this 
subject  by  stating  that  glands  may  form  a  secretion  exierne  by  with- 
drawing substances  from  the  blood,  and  also  a  secretion  interne  by 
passing  their  products  into  the  blood.  He  illustrated  this  conception 
by  referring  especially  to  the  liver  which,  in  addition  to  its  external 
secretion,  the  bile,  also  furnishes  an  internal  agent  which  is  directly 
concerned  in  the  aggregation  of  glycogen  and  the  formation  of  sugar. 
In  1889,  Brown-Sequard,  then  72  years  of  age,  announced  to  the  Societe 
de  Biologic  de  Paris  that  he  had  carried  out  upon  himself  a  series  of 
experiments  wath  extract  of  testicle,  proving  that  this  therapy  "has 
given  him  much  physical  strength,  an  invigoration  of  cerebral  function, 
and  a  good  appetite  and  digestion. "  Then  followed  a  period  of  organo- 
therapy during  which  practically  every  organ  of  the  body  was  tested 
as  to  its  remedial  qualities  in  diseases  supposedly  produced  by  a 
deficiency  of  some  internal  secretion.  Much  of  this  material,  however, 
is  absolutely  valueless,  because  aggrandized  for  purposes  of  commercial 
exploitation. 

Brown-Sequard  has  added  to  the  conception  of  Bernard  the  idea 
that  certain  glands  secrete  certain  specific  substances  into  the  blood- 
stream, tending  to  produce  a  definite  correlation  of  function  between 
different  organs.  This  interpretation  of  facts  really  forms  the  basis 
of  a  new  function.     Several  years  later  Schiff  compiled  additional 

1  For  references  see:  Biedl,  The  Internal  Secretory  Organs,  translated  by 
Williams,  Wood  &  Co..   1913. 

-  Archiv  fiir  Anat.,  Physiol,  und  wissensch.  Medizin,  1849,  42. 
3  Legons  de  physiol.  exper.,  Paris,  1855. 

951 


952  THE    INTERNAL    SECRETIONS 

data  pertaining  to  the  effects  following  the  removal  of  the  thyroid 
bodies  which  were  based  in  the  main  on  the  clinical  observations  of 
J.  L.  and  A.  Reverdin  and  Kocher  on  post-operative  myxedema. 
Somewhat  later  Glover,  Schafcr  (1895),  Cybulski  (1895),  Biedl  (1898) 
and  Dreyer  (1899)  studied  the  action  of  suprarenal  extract  upon  the 
cardio-vascular  system.  In  all  these  instances,  it  was  shown  that  our 
body  contains  certain  aggregates  of  cells  which  possess  an  altruistic 
function,  because  they  supply  the  organism  as  a  whole  with  substances 
having  to  do  with  its  general  welfare.  The  medium  through  which 
these  organs  are  able  to  exert  this  influence,  is  the  blood  or  more  par- 
ticularly the  blood  plasma. 

Classification  of  the  Internal  Secretions. — In  1902,  Bayliss  and 
Starling  showed  that  a  flow  of  pancreatic  juice  may  be  evoked  by 
means  of  some  agent  derived  from  the  mucous  membrane  of  the  duo- 
denum. To  this  substance  these  investigators  applied  the  name  of 
secretin.  At  about  the  same  time  Starling  and  Claypon  demonstrated 
the  existence  of  a  similar  stimulant  in  the  female  generative  organs 
which  induces  a  growth  of  the  mammary  glands.  Starling,  therefore, 
proposed  to  apply  to  all  these  chemical  agents  or  messengers  the  name 
of  "hormone,"  from  the  Greek  SpfJ-doi},  to  stir  up  or  excite.  But  in- 
asmuch as  some  of  these  cellular  products  may  also  retard  a  function, 
Schafer^  advises  to  include  all  of  them  under  the  general  term  of  auta- 
coid  substances,  from  the  Greek  a/cos,  a  remedy  and  avTos,  natural. 
Thus,  an  autacoid  represents  any  drug-like  principle  which  is  produced 
in  the  internal  secreting  tissues  and  organs.  In  accordance  with  their 
action,  these  substances  may  then  be  grouped  as  hormones  or  chalones 
(Greek  x^Xaco,  to  make  slack).  The  former  are  excitatory  and  the 
latter  inhibitory  in  their  nature. 

In  most  instances  these  internal  agents  are  as  yet  wholly  unknown 
to  us  chemically,  and  their  presence  can  only  be  detected  in  an  experi- 
mental way.  In  some  cases,  however,  they  have  been  isolated,  and 
have  been  dealt  with  as  definite  chemical  entities.  Carbon  dioxid  is  a 
substance  of  this  kind,  because  it  plays  the  part  of  a  hormone  in  stimu- 
lating the  respiratory  center  whenever  produced  in  excess.  Another 
one  is  adrenalin,  a  crystalline  body  obtained  from  the  adrenal  glands  by 
Takamine.2  It  constricts  the  blood-vessels  and  raises  the  blood  pres- 
sure. As  a  third  might  be  mentioned  hydrochloric  acid,  because  it 
liberates  secretin  and  as  a  fourth,  idiothyrin  which  exerts  a  peculiar 
action  upon  the  neuro-muscular  mechanism.  By  far  the  greatest 
number  of  these  autacoids,  however,  are  of  unknown  composition  and 
their  presence  can  only  be  proved  physiologically,  for  example,  by  in- 
jecting the  extracts  of  the  tissues  in  which  they  are  supposed  to  exist 
into  the  blood-stream. 

Starling  emphasizes  the  fact  that  hormones  belong  to  the  crystal- 
loids rather  than  to  the  colloids.     Consequently,  they  are  relatively 

1  Intern.  Congress  of  Med.,  1913. 

2  Therap.  Gazette,  xvi,  1901,  221. 


THE    THYROID    AND    PARATHYROID    BODIES 


953 


stable  substances  and  may  be  subjected  to  ordinary  degrees  of  heat 
without  losing  their  function,  a  fact  which  sharply  differentiates  them 
from  the  ferments  and  enzymes.  To  be  sure,  both  these  agents  are 
cellular  products,  but  while  the  autacoids  are  d(!structible  and  their 
function  is  restrictetl  to  the  domain  of  the  body,  the  enzymes  are  not 
limited  in  this  way.  Moreover,  they  are  resistant,  and  are  not  changed 
during  the  processes  evoked  by  them. 

Any  other  classification  of  the  autacoids  meets  with  the  difficulty 
that  they  act  upon  specific  groups  of  cells  and  that  the  effect  produced 
by  them  is  usually  rather  vague  in  character.  Thus,  while  the  action 
of  adrenin  is  quite  obvious,  other  internal  secretions,  for  example, 
those  of  the  thyroids  and  thjinus,  possess  a  general  metabolic  function 
which  it  is  difficult  to  analyze.  Gley,  ^  however,  suggests  the  following 
classification : 


(a)  Nutritive 


(6)  Harmozones 


IGlycose,  liver, 
Fat,  intestinal  mucosa, 
Albumins  of  blood,  intestinal  mucosa  and  blood. 

1.  Substances  effecting    f  sugar  metabolism,  pancreas, 
nutritive  changes        I  sugar  mobilization,  adrenals, 

2.  Substances  helping      ( 

to  maintain  int.  me-    \  antithrombin,  liver, 
dium  I 

testicles, 

ovaries, 


3.  Morphogenetic 


thyroid, 

hypophysis, 

thymus. 


(c)  Hormones 


(p,       •     1  /  activating  the  trypsin,  spleen, 
1  catabolic,  thyroid, 
f  secretin,  duodenum 
I  Physiological  \  adrenin,  adrenals, 

I  galactogogue,  placenta. 


,j^  -n    1  /  Carbon  dioxid,  muscles  and  glands, 

(a)  Parhormones  s  t-         i- 

I  Lrea,  liver. 

An  inspection  of  this  table  must  show  immediately  that  this  clas- 
sification is  by  no  means  sufficiently  embracing  to  include  all  of  the 
internal  secretions  in  their  proper  relation  to  one  another  and  hence, 
it  may  be  permissible  to  arrange  them  in  accordance  with  their  location 
rather  than  their  function.  In  the  first  place,  it  is  to  be  noted  that 
these  secretions  originate  in  the  so-called  endocrine  organs  (Greek  'ivdov 
within,  and  /cptvco  to  separate),  including  the  thyroids,  parathyroids, 
thymus,  duodenum,  liver,  pancreas,  adrenals,  pineal  gland,  pituitarj' 
body,  placenta,  choroid  plexus,  and  the  testes  and  ovaries.  Every  one 
of  these  glands  presents  at  least  three  of  the  characteristics  ordinarily 
assigned  to  an  internal  secretory  structure,  namely:  (a)  the  cells  com- 
posing them  are  usually  arranged  in  the  form  of  acini,  and  embrace  a 
certain  amount  of  granular  and  other  material  from  which  the  secretion 

1  The  Internal  Secretions,  translated  by  Fishberg,  Hober,  New  York,  1917. 


954 


THE    INTERNAL    SECRETIONS 


may  be  derived.  Furthermore,  while  not  in  possession  of  a  true  duct, 
they  lie  in  close  relation  with  definite  efferent  and  afferent  blood-vessels 
and  lymphatic  channels,  (6)  their  product  can  be  isolated  chemicallj^ 
from  their  venous  blood  or  lymph,  (c)  their  substance  or  the  blood 
or  lymph  returned  from  them,  may  be  shown  to  possess  a  specific 
physiological  action,  and  (d)  the  removal  of  the  organ  is  followed  by  a 
loss  of  a  definite  function  which  is  absolutely  essential  to  the  health 
and  very  existence  of  the  animal. 

A.  THE  THYROID  AND  PARATHYROID  BODIES 

Position  and  Structure  of  the  Thyroid  Gland. — In  the  cat,  dog 
and  man,  the  thyroid  gland  (Greek :  thyreos,  shield)  consists  of  a  right 
and  left  lobe  which  are  connected  with  one  another  by  a  bridge  or 
isthmus  of  the  same  tissue  extending  transversely  across  the  trachea. 
These  lobes  are  nearly  equal  in  size,  and  measure  about  5  cm.  in  length. 


Fig.  503.  Fio.  504. 

Fig.  503. — Diagram  Showing  the  Position  of  the  Thyroid  Gland. 
TC,  thyroid  cartilage;  TG,  thyroid  gland;  T,  Trachea.     The  parathyroids  are  indi- 
cated in  black. 

Fig.  504. — Diagrammatic  Representation  of  the  STRrcTURE  of  Human  Thyroid 

Their  combined  weight  amounts  to  30  or  40  grams,  but  these  figures 
are  only  approximate,  because  the  vascularity  of  this  organ  is  subject 
to  considerable  fluctuations.  It  is  generally  larger  in  females,  and 
increases  in  size  during  the  menstrual  period.  During  adult  life  it 
shows  a  proportion  to  the  weight  of  the  body  of  1:  1800  and  during 
infancy  a  proportion  of  1 :  250;  hence,  it  is  much  larger  during  the  latter 
period. 

The  thyroid  is  developed  from  an  outgrowth  of  the  primitive 
pharynx  and  is,  therefore,  of  hj^poplastic  origin.  It  is  enveloped  by  a 
layer  of  dense  areolar  tissue  which  also  subdivides  its  substance  into 
small  lobules  of  irregular  size.     Its  tissue  is  composed  of  a  large  number 


THE    THYROID    AND    PAKATHYROID    HODIES  955 

of  vesicles  which  are  hned  by  a  single  row  of  cuboidal  or  columnar  epi- 
thelium, and  contain  a  peculiar  colloid  materia  .  The  size  and  shape 
of  these  vesicles  differ  greatly ;  some  of  them  attaining  a  diameter  of 
1.0  mm.  Langendorff  states  that  these  acini  are  made  up  of  two  types 
of  cells,  because  while  some  of  them  appear  to  have  reached  adult  size 
and  to  be  actively  secreting,  others  seem  to  be  held  in  reserve  until 
called  upon  to  take  the  places  of  those  torn  away  and  discharged  in  the 
secretion. 

The  thyroid  is  a  very  vascular  organ,  receiving  560  c.c.  of  blood 
per  100  grams  of  substance  in  the  course  of  a  minute.^  Its  five  supply 
channels  are  the  right  and  left  superior  and  inferior  thyroid  arteries, 
branches  of  the  external  carotid,  and  the  thyroidea  ima,  which  ascends 
upon  the  trachea  and  is  a  branch  of  the  subclavian  arteries.  Each 
lobe  is  drained  by  three  collecting  channels,  namely  the  superior, 
middle  and  inferior  thyroid  veins.  This  gland  is  also  equipped  with 
an  intricate  system  of  lymphatics  which,  however,  do  not  communi- 
cate directly  with  the  colloid  vesicles.  Its  nerve  supply  is  derived 
from  the  superior  and  inferior  laryngeal  nerves. 

Position  and  Structure  of  the  Parathyroid  Glands. — The  parathy- 
roids- usuall}'  present  themselves  as  four  small  rounded  masses  em- 
bedded in  the  substance  of  the  thyroid.  They  are  oval  in  shape, 
measuring  about  6  mm.  in  length  and  3  to  4  mm.  in  breadth,  and  their 
combined  weight  rarely  exceeds  0.10  gram.^  One  pair  of  them  is 
usually  found  near  the  level  of  the  lower  border  of  the  cricoid  carti- 
lage, between  the  wall  of  the  esophagus  and  the  lateral  mass  of  th'e 
thyroid,  while  the  second  is  situated  as  a  rule  opposite  the  third  or 
fourth  ring  of  the  trachea  in  or  near  the  lower  pole  of  each  lobe.^ 
Accessory  parathyroids  are  encountered  at  times  along  the  trachea 
and  even  in  the  cavity  of  the  thorax. 

The  cells  composing  these  bodies  are  epithelial  in  character  and 
are  arranged  in  palisade-like  columns  which  are  connected  with  one 
another  by  unusually  vascular  connective  tissue.  In  many  cases 
this  tissue  is  so  well  developed  that  the  entire  gland  appears  to  be  sub- 
divided into  many  smaller  lobules.  Its  parenchyma  is  made  up, 
on  the  one  hand,  of  large  polygonal  chief  cells,  the  cytoplasm  of  which 
does  not  stain  well,  and,  on  the  other,  of  cells  possessing  a  delicate, 
granulated  interior  which  stains  intensely  with  eosin  and  other  acid 
dyes.  The  parathyroids  may  also  contain  follicles  which  are  filled 
with  a  colloidal  material  similar  to  that  occupying  the  vesicles  of  the 
thyroid. 

Extirpation  of  the  Thyroid  and  Parathyroids. — It  was  formerly 
believed    that  the  thyroid  regulates  the  blood-suppl}^  of  the  brain 

1  Tschuewsky,  Pfliiger's  Archiv,  xcvii,  1903,  210. 

2  Discovered  by  Sandstrom,  Upsala  Lakarefor.  Forh.,  xv,  1880,  and  described 
by  Kohn,  Archiv  fiir  mikr.  Anat.,  xlv,  1895. 

^  Thomson,  The  Thyroids  and  parathyroids  throughout  vertebrates,  Phil. 
transact.,  Roy.  Soc,  1911. 

*  Fischer,  Archiv  ftir  Anat.,  1911. 


956  THE    INTERNAL    SECRETIONS 

(Cyon),  this  view  being  based  upon  the  fact  that  it  is  placed  directly 
in  the  path  of  the  cerebral  vessels  and  contains  at  times  anastound- 
ingly  large  amount  of  blood. ^  The  latter  peculiarity,  in  particular, 
led  Tiedemann  to  assume  that  it  is  a  blood-forming  organ.  Its  real 
nature,  however,  was  not  detected  until  the  3^ear  1856,  when  Schiff^ 
proved  that  its  total  removal  induces  certain  pathological  conditions 
which  invariably  prove  fatal  in  the  course  of  three  to  four  weeks.  In 
spite  of  these  perfectly  definite  results,  the  removal  of  this  organ  was 
resorted  to  a  number  of  times  in  subsequent  years  for  the  relief  of 
those  serious  respiratory  difficulties  which  are  usually  associated 
with  goiter.  In  all  these  cases,  this  surgical  procedure  was  followed 
by  very  alarming  symptoms  which  presented  themselves  chiefly  as 
disorders  in  nutrition  and  a  general  muscular  weakness,  tremors  and 
spasms.^  In  1884,  SchilT  operated  upon  a  second  series  of  sixty  dogs 
of  which  fifty-nine  died  within  three  weeks.  This  study  drew  renewed 
attention  to  this  organ,  and  spirited  efforts  were  made  henceforth  to 
unravel  its  function.  Thus,  it  was  soon  discovered  that  the  serious 
s\anptoms  following  its  total  extirpation,  could  be  prevented  by  per- 
mitting a  portion  of,  say,  its  lower  extremity,  to  remain  in  the  body.^ 
Likewise,  it  was  shown  that  the  transplantation  of  the  thyroid  to  some 
other  part  of  the  body,  such  as  the  peritoneal  cavity,  protects  the 
animal  against  the  consequences  of  thyroidectomy.  The  healing  in  of 
these  transplanted  segments  of  the  gland  proceeds  very  quickly  in 
thyroidectomized  animals  so  that  their  vascularization  is  practically 
completed  at  the  end  of  the  third  week.  In  the  normal  animal,  on 
the  other  hand,  these  transplants  do  not  grow  well  and  do  not  attain 
this  stage  in  less  than  eight  weeks. ^  Lastly,  Vassale^  proved  that 
the  alarming  effects  of  thja-oidectomj^  may  also  be  obviated  by  the  feed- 
ing of  th3Toid  substance  or  the  injection  of  th3'roid  extract.  The 
conclusion  to  be  derived  from  experiments  of  this  kind  is  that  the 
thyroid  furnishes  an  agent  which  is  absolutely  essential  to  life. 
The  S5rmptoms  Following  Thyroidectomy. — The  effects  of  ex- 
tirpation of  the  thyroid  and  parathyroids  differ  in  different  animals, 
obviously  because  these  structures  vary  in  their  size  and  position.  In 
the  herbivora,  for  example,  the  parathyroids  generally  lie  outside 
the  substance  of  the  thj-roid,  while  other  animals  are  in  possession  of 
accessory  parathyroids  which  are  scattered  as  small  globular  masses 
along  the  trachea.  In  the  fishes,  these  bodies  are  represented  bj'  small 
patches  of  tissue  of  about  the  size  of  the  head  of  a  pin  which  are  situated 

1  Swale  Vincent,  Ergebn.  der  Phj'^siol.,  ix,  1911. 

^  Unters.  iiber  Zuckerbildung,  Wurzburg,  1S59.  Previous  to  this  time  we 
have  the  experiments  of  Astley  Cooper,  Rapp  and  Bardeleben  which,  however, 
led  to  no  definite  results. 

'  Reverdin  (Rev.  med.  de  la  Suisse  romande,  1882);  Kocher  (Archiv  fiir  klin. 
Chir.,  1883),  and  Billroth  (Wiener  med.  Presse,  1877). 

*  Eiselberg,  Wiener  klin,  Wochenschr.,  v,  1892,  81. 

5  Salzer,  ibid.,  1909. 

6  Neur.  Zentralblatt,  1891. 


THE    THYROID    AND    PARATHYROID    RODIES  957 

along;  the  aorta  aiul  along;  the  arciios  of  the  gills.  If  w(^  confino  our- 
selves, therefore,  to  the  eaiiiivora  and  include  in  this  discussion  the 
symptoms  caused  by  the  enucleation  of  the  parathyroids,  the  following 
clinical  picture  is  obtained. 

The  features  are  swollen  and  imperfectly  outlined,  owing  to  an 
edematous  condition  of  the  skin  which  in  turn  is  caused  by  an  a(!cumu- 
lation  of  mucin  in  the  subcutaneous  connective  tissue.  Later  on,  the 
bloated  appearance  of  the  skin  is  aggravated  by  a  certain  roughness 
and  dryness,  which  finds  its  origin  in  the  cessation  of  the  cutaneous 
secretions  and  eventually  gives  rise  to  a  coarseness  and  falling  out  of  the 
hairs.  This  infiltration  also  affects  the  mucous  membranes,  and 
eventually  involves  the  respiratory  passage  and  conjunctional  sacs 
(myxedema).  The  animal  loses  weight  steadily,  and  finally  enters 
a  condition  of  pronounced  malnutrition,  the  so-called  cachexia  thyreo- 
priva  (strumipriva).  But  these  purely  metabolic  disturbances  which 
prove  that  thyroidectomy  renders  the  animal  unfit  to  utilize  its  food, 
are  invariably  associated  with  others,  indicating  a  severe  intoxication  of 
the  nervous  system.  To  begin  with,  it  is  observed  that  the  muscular 
contractions  become  clonic  in  their  character,  then  tetanic  and  lastly, 
spastic.  This  leads  to  a  marked  muscular  rigidity  and  contracture, 
and  finally  to  a  weakness  as  well  as  a  motor  and  sensory  paralysis  of 
the  entire  body.  As  the  anterior  and  posterior  extremities  become 
weakened  and  are  no  longer  able  to  support  the  trunk,  the  animal  is 
forced  to  assume  the  position  usually  occupied  by  it  during  sleep.  The 
muscular  tremors  are  gradually  intensified  and  become  more  general 
in  their  character,  terminating  eventually  in  severe  convulsions  and 
death.  Although  the  higher  nerve  centers  appear  to  retain  their  func- 
tion for  a  relatively  long  period  of  time,  their  irritability  is  gradually 
diminished,  which  renders  the  animal  stupid  and  very  apathetic. 
Death  usually  results  in  the  course  of  9  to  12  days. 

Cretinism,  Myxedema  and  Hyperthyroidism. — Keeping  the  char- 
acter of  the  symptoms  just  cited  clearly  in  mind,  we  are  now  in  a  better 
position  to  analyze  the  clinical  pictures  of  cretinism,  myxedema, 
hyperthyroidism,  exophthalmic  goiter,  and  the  conditions  forming  the 
basis  of  Basedow's  disease.  In  a  general  way,  it  may  be  said  that  man 
is  subject  either  to  a  diminished  or  an  increased  function  of  the  thyroid 
gland,  or,  in  other  words,  to  a  deficient  or  an  excessive  formation  of 
this  internal  secretion. 

(a)  Cretinism  or  infantilism  is  due  either  to  an  imperfect  development  of  the 
thyroid  gland  or  to  its  atrophy  in  later  years.  The  infant  so  afflicted  presents  a 
dwarfed  appearance,  because  the  growth  of  the  bones  and  soft  parts  has  been 
checked.  The  abdomen  is  large  and  pendulous,  while  the  legs  are  poorly  formed 
and  seem  scarcely  able  to  support  the  weight  of  the  trunk.  The  face  presents  a 
swollen  appearance  and  imperfectly  outlined  contours.  The  hair  is  coarse  and 
scanty  and  the  skin  thick  and  dry.  Mentally,  the  cretins  are  far  behind  children 
of  the  same  age,  in  fact,  their  intelligence  frequently  borders  upon  imbecility  and 
idiocy.  Their  movements  are  clumsy  and  unsteady.  In  many  instances,  this  con- 
dition of  infantile  myxedema  or  cretinism  resembles  very  closely  true  dwarfism, 


958 


THE    INTERNAL    SECRETIONS 


and  certain  types  of  rachitis  fetalis  from  which  it  must,  therefore,  be  differentiated. 
This  cUnical  picture  may  be  cleared  up  in  the  course  of  a  month  or  two  by  the  feeding 
of  thyroid  substance  or  of  an  extract  of  thyroid.  Growth  begins  again,  the  myxe- 
dematous symptoms  disappear  more  or  less  completelj-,  and  the  infant  brightens 
up  perceptiblj'  from  week  to  week.  In  our  own  country  myxedematous  cretinism 
is  rather  rare,  but  there  are  several  regions  in  which  it  is  endemic;  for  example, 
in  Italy  which  reported  13.000  cases  in  1883,  and  in  Austria,  Savoy,  the  Pyrenees, 
the  Himalayas  and  the  Cordilleras.  Since  these  districts  are  mountainous  and 
are  formed  by  marine  deposit  of  the  Paleozoic,  Triassic  and  Tertiary  periods, 
cretinism  has  been  etiologically  referred  to  peculiarities  of  the  soil  and  to  the 
drinking  water  derived  from  these  geological  strata.     That  there  is  some  truth  in 


Fig.  505.- 


-Cketin  before  (A)  and  after  (B;  Treatmext  with  Sheep's  Thyroid. 
{Nicholson,  in  Arch.  ofPed.,  June,  1900.) 


this  explanation  is  shown  by  the  fact  that  the  introduction  of  fresh  water  from 
other  sources  has  eradicated  this  disease  in  at  least  some  of  these  districts.  More- 
over, it  is  a  matter  of  common  experience  among  these  people  that  the  drinking 
of  water  from  so-called  "goiter-springs"  gives  rise  to  m^'xedematous  symptoms 
within  a  short  time,  while  filtered  or  boiled  water  does  not.^ 

(6)  Myxedema. — The  extirpation  or  atrophy  of  the  thjToid  gland  in  adults  is 
soon  followed  by  symptoms  such  as  have  just  been  described.  The  skin  becomes 
thickened,  swollen  and  dry  and  yields  mucin  when  extracted  with  alkali.  The  hair 
becomes  coarse  and  scanty.  There  is  also  present  a  general  fatigue,  a  mental 
apathy,  and  a  tendency  to  an  abnormal  deposition  of  fat.  The  nitrogen  metab- 
olism is  reduced. 

^  Bircher,  Zeitschr.  fiir  exp.  Path,  und  Ther.,  ix,  1911. 


THE    THVUOII)    AND    PAKATIIYROIl)    HODIES 


959 


(c)  Hyperthyroidism. — The  condition  of  liyperthyroidism  may  be  produced  in 
animals  either  by  the  continued  feeding  of  thyroid  substance  or  by  the  intraven- 
ous injection  of  thyroid  extract  (ral)bits).  It  is  usually  initiated  by  frequent  at- 
tacks of  tachycardia  to  which  are  added  disorders  of  digestion  and  metabolism, 
such  as  diarrhea,  intestinal  hemorrhage,  emaciation,  poljoiria  and  glycosuria. 
A  few  cases  are  also  on  record  of  persons  who  have  taken  excessive  amounts  of 
thyroid  for  the  relief  of  obesity  and  other  disorders.  Thus,  one  person  ingested 
in  the  course  of  five  weeks  nearly  1000  tablets  of  thyroid  substance  of  about  0.3 
gram  each  and  developed,  in  addition  to  the  syin  ptoms  just  mentioned,  an  extreme 
irritability  of  the  nervous  system,  psychic  exultation,  sh-eplessness  and  trembling 
of  the  muscles.'  This  complex  of  symptoms  corresponds  almost  precisely  with 
that  presented  by  persons  suffering  from  Basedow's  disease  or,  as  it  is  now  more 
commonly  called.  Graves'  disease.     In  1840,  Basedow  showed  that  the  combination 


Fu..  jlJG. -^Exophthalmic  Goiter. 

The  patient  shows  a  goiter  of  moderate  size;  great  exophthalmos,  .smooth  forehead, 
and  abnormal  expression.     (MacCallum.) 

of  exophthalmos,  goiter  and  tachj^cardia  forms  a  syndrome  of  a  not  infrequent 
clinical  condition  which,  in  general,  is  just  the  reverse  of  that  noted  in  thyreopiiva, 
hypothyroidism  or  diminished  thyroid  function.  The  heart  is  very  rapid  and 
often  irregular;  the  temperature  is  usually  a  degree  or  two  above  normal;  the  thy- 
roid is  generally  somewhat  enlarged ;  while  the  eyes,  owing  to  the  wide  open  condi- 
tion of  the  eyelids,  are  very  prominent  and  staring.  To  these  three  fundamental 
symptoms,  others  have  been  added  in  the  course  of  more  recent  years,  the  combined 
clinical  picture  being  that  of  Graves'  disease.  Among  the  secondary  conditions 
might  be  mentioned  an  increased  appetite  and  metabolism,  insomnia,  restlessness, 
intensified  sensations,  mental  excitement  accompanied  by  hallucinations,  muscular 
tremors,  anemia  and  loss  of  weight. 

The  etiological  connection  of  Graves'  disease  with  a  hyperactivity    of   the 

^  The  therapeutics  of  preparations  containing  the  active  principles  of  the 
internal  secretions,  is  discussed  in  Harrower's  "Practical  Hormone  Therapy," 
Hober,  New  York,  1914. 


960  THE    INTERNAL    SECRETIONS 

thyroid  and  a  flooding  of  the  system  with  an  excessive  amount  of  this  secretion, 
is  well  illustrated  by  the  fact  that  the  partial  extirpation  of  this  organ  gives  rise  to 
an  almost  immediate  amelioration  of  these  symptoms.  In  fact,  in  many  cases 
it  suffices  to  reduce  the  vascularity  of  this  organ  by  the  ligation  of  one  of  its  arteries. 
Kocher  states  that  these  operative  measures  resulted  in  76  per  cent,  of  his  cases  in  a 
complete  cure  and  in  another  14  per  cent,  in  a  decided  improvement.  The  mor- 
tality which  amounts  to  about  3  per  cent.,  is  referable  chiefly  to  erroneous  diag- 
nosis. Simple  hyperthyrosis  is  characterized  by  a  slight  swelling  of  this  gland,  i.e., 
by  a  latent  increase  in  its  size  and  a  few  of  the  milder  symptoms  enumerated  above. 
It  occurs  most  frequently  in  young  women,  and  is  temporary  in  its  nature 

The  Nature  of  the  Active  Principle  of  the  Thyroid. — Much  un- 
certainty still  prevails  regarding  the  nature  of  the  active  agent 
contained  in  the  secretion  of  this  gland,  although  it  seems  established 
that  it  is  derived  from  the  colloid  material  of  its  vesicles.  In  this  connec- 
tion, it  is  of  interest  to  note  that  a  substance  has  been  isolated  from 
thyroid  tissue  by  Baumann,^  to  which  he  has  given  the  name  of 
iodothyrin  or  thyroidin.  It  contains  as  much  as  9.3  per  cent,  of  its 
dry  weight  as  iodin.  While  the  action  of  this  substance  has  not  been 
definitely  ascertained,  it  seems  certain  that  it  is  at  least  closely 
associated  with  the  activity  of  this  gland.  This  is  shown  by  the  fact 
that  it  is  always  present  in  normal  glands  and  that  the  minimun  amount 
of  iodin  necessary  to  maintain  the  usual  histological  picture  of  thyroid 
tissue,  does  not  fluctuate  materially  in  any  given  species.  Moreover,  in 
cases  of  hyperplasia  the  iodin  content  is  invariably  below  the  minimum 
value  of  0.1  per  cent,  of  the  dried  gland;  in  fact,  no  demonstrable 
quantities  of  this  substance  are  ever  present  in  extreme  conditions  of 
goiter.  Very  beneficial  results  have  been  obtained  with  this  substance 
in  the  treatment  of  myxedema  and  goiter.  Hunt^  furnishes  the  fol- 
lowing interesting  analyses: 

Per  cent,  of 
Thyroid  of  ,  iodin 

Children None 

Maltese  kid None 

Guinea-pig 0 .  05 

Dog 0 .  06 

Cat 0.08 

Sheep 0.17 

Beef 0.25 

Hog 0.33 

Human 0 .  23 

Human  in  goiter 0 .  04 

A  similar  but  less  complex  body  has  recently  been  isolated  by 
KendalP  which  he  calls  thyro-oxy-indol  or  thyroxin  and  to  which  he 
gives  the  formula:  C11H10O3NI3.  It  is  claimed  that  this  substance 
exerts  as  powerful  an  influence  upon  cretinism  and  myxedema  as 
desiccated  thyroid.  Thus,  it  may  be  concluded  that  the  active  prin- 
ciple of  this  internal  secretion  is  an  iodin-containing  hormone,  the 

1  Zeitschr.  fiir  physiol.  Chemie,  xxi,  1896,  481. 

2  Studies  on  Thyroid,  Bull.  Hygienic  Lab.,  Washington,  1909,  No.  47. 
'  Am.  Jour,  of  Physiol.,  Proc,  xlv,  1918. 


THE    THYROID    AND    PARATHYROID    DODIES  9G1 

efficacy  of  which  does  not  dcpciul  so  niucli  upon  the  iodin  as  upon 
the  character  of  its  conihinalion  with  other  substances.  But  since 
organic  iodin  complexes,  sucli  as  iotlin-protein,  an;  inactive,  the  chief 
factor  to  be  determined  is  how  much  active  iodin-containing  material 
can  actually  be  liberated  from  the  inactive  iodin  substance  of  the 
gland. 

In  order  to  prove  that  such  an  elaboration  actually  takes  place, 
Rogoff  and  INIarine'  have  followed  the  method  of  Gudernatch^  and 
have  exposed  tadpoles  to  the  influence  of  iodin-frce  and  hydrolized 
sheep  thyroid,  containing  varying  amounts  of  available  iodin.  In 
the  latter  case,  their  growth  was  retarded,  while  their  tlifferentiation 
took  place  at  a  much  faster  rate.  The  rapidity  and  decisiveness  with 
which  these  changes  are  effected,  may  be  employed  as  a  means  of 
determining  the  intensity  of  the  evolution  of  the  active  iodin-con- 
taining  substance. 

A  chemical  test  of  even  greater  delicacy  is  the  nitrite  reaction  described  by- 
Hunt.'  If  so  little  as  0.1  mg.  of  dried  thyroid  substance  per  gram  of  body-weight 
is  fed  to  a  white  mouse  each  day  for  10  consecutive  days,  this  animal  will  survive 
as  much  as  10  times  the  amount  of  acetonitrile  which  would  prove  fatal  to  any 
other  mouse  not  having  received  this  treatment. 

It  is  also  of  interest  to  note  that  the  thyroid  possesses  marked  storative  quali- 
ties for  iodin.  Thus,  if  iodin  is  administered  to  animals  with  actively  hyperplas- 
tic thyroids,  this  substance  is  rapidly  stored  in  this  gland  and  gives  rise  tc  definite 
histological  changes,  constituting  the  so-called  colloid  goiter.  Moreover,  the 
greatest  storative  power  is  possessed  by  those  glands  which  are  most  hyperplastic 
and  contain,  to  begin  with,  the  smallest  amount  of  iodin.  It  mattcrslittle  whether 
the  iodin  is  administered  at  this  time  intravenously  in  the  form  of  a  salt  or  is  per- 
fused through  the  excised  gland. 

The  Function  of  the  Thyroid  and  Parathyroids. — It  has  been 
noted  above  that  the  extirpation  of  the  thyroid  of  carnivorous  animals 
proves  fatal  almost  without  exception,  but  does  not  seriously  incon- 
venience the  herbivora.  Whatever  deviations  from  this  general  rule 
may  have  been  observed,  they  are  due  in  all  probability  to  peculiar- 
ities in  the  distribution  of  the  parathyroid  bodies.  Inasmuch  as  these 
structures  were  not  recognized  as  an  anatomical  entity  until  late  dur- 
ing the  period  of  thyroid  experimentation,  many  of  these  symptoms 
have  undoubtedly  been  ascribed  to  the  loss  of  this  organ,  although 
actually  caused  by  the  loss  of  the  parathyroids.  Besides,  since  the 
latter  also  appear  in  the  form  of  accessory  masses  along  the  trachea, 
they  may  have  escaped  detection  altogether.  It  need  not  surprise  us, 
therefore,  to  find  that  the  clinical  picture  following  the  removal  of  the 
thyroid  and  parathyroids,  remained  incomplete  for  some  time  after 
the  beginning  of  this  kind  of  experimentation. 

Very  shortly  after  the  discovery  of  the  parathyroids,  Gley  and 
others  proved  that  the  symptoms  following  the  extirpation  of  the  thy- 

1  Jour,  of  Pharm.  and  Exp.  Therapeutics,  ix,  1916,   57  and  x,  1917,  99. 

2  Archiv  fUr  Entwick.  Mech.  der  Organe,  xxxv,  1913,  457;  also  see:  Graham, 
Jour.  Exp.  Med.,  xxiv,  1916,  345. 

'  Jour,  of  Biol.  Chem.,  1,  1905,  33. 
61 


962  THE  INTERNAL  SECRETIONS 

roid,  are  markedly  different  from  those  produced  by  the  removal  of  the 
parathyroids.  This  general  fact  becomes  apparent  immediatelj^  if 
the  symptoms  enumerated  above  are  subjected  to  a  re-examination. 
It  will  then  be  noted  that  they  arrange  themselves  in  two  groups,  one  of 
which  is  characterized  by  disorders  of  metabolism,  such  as  malnutri- 
tion and  cachexia,  and  the  other,  by  defects  of  nervous  function,  such 
as  muscular  tremors  and  tetany.  Recent  investigations  have  fully 
confirmed  this  deduction  so  that  it  may  be  regarded  as  certain  that 
thyroidectomy  gives  rise  to  a  state  of  malnutrition,  terminating  in  the 
condition  of  cachexia  thyreopriva,  while  parathyroidectomy  results  in 
muscular  tremors  and  spasms,  forming  the  clinical  picture  of  tetania 
]>arat}ujreopriva.  Consequently,  the  combination  of  these  two  com- 
plexes of  symptoms  cannot  be  due  to  an  overlapping  of  the  functions 
of  these  two  types  of  tissue,  but  must  be  caused  by  their  simultaneous 
destruction  or  atrophy. 

While  no  definite  statements  can  be  made  at  this  time  regarding 
the  manner  in  which  the  thyroid  exerts  its  peculiar  metabolic  action, 
it  may  be  surmised  that  it  develops  a  specific  hormone  which  facilitates 
the  chemical  reductions  in  other  tissues,  chief  among  which  is  the  ner- 
vous tissue.  First  of  all,  this  agent  increases  the  total  metabolism, 
as  is  evinced  by  a  greater  excretion  of  nitrogen,  carbon  dioxid  and 
phosphoric  acid,  and  a  greater  consumption  of  oxygen.  Upon  this 
fact  rests  the  therapeutic  value  of  thyroid  feeding  in  obesity,  but  since 
in  this  case  the  difficulty  does  not  lie  in  the  protein  metabolism,  thyroid 
feeding  as  a  remedial  measure  against  adiposity  in  the  absence  of  an 
actual  inactivity  of  the  thyroid  is  a  dangerous  procedure.  It  may 
produce  organic  defects  of  the  heart  and  other  pathological  lesions.  In 
this  connection  it  should  also  be  noted  that  the  feeding  of  animals 
with  excessive  amounts  of  meat  may  give  rise  to  goiter  and  rickets, 
and  that  this  outcome  may  be  prevented  by  the  simultaneous  ingestion 
of  milk,  bread  and  bones.  No  definite  explanation  can  be  offered  for 
the  hypertrophy  and  hyperplasia  of  the  thyroid  occurring  during  the 
menstrual  period  and  pregnancy.  It  cannot  be  doubted,  however, 
that  it  indicates  a  close  functional  correlation  between  the  different 
endocrine  organs,  and  offers  a  plausible  explanation  for  the  peculiar 
metabolic  and  nervous  symptoms  exhibited  by  women  during  these 
periods. 

The  picture  of  tetany  following  the  removal  of  the  parathyroids, 
is  very  similar  to  that  obtained  in  infantile  tetany,  the  convulsions  in- 
cited by  gastro-intestinal  disorders,  eclampsia,  and  other  conditions. 
It  consists  in  a  gradually  increasing  stiffness  or  rigor  of  the  entire  body, 
trembling,  clonic  and  tonic  spasms  of  the  muscles,  as  well  as  a  loss  of 
muscular  coordination  and  strength.  The  body-temperature  rises, 
the  frequency  of  the  heart  and  respiration  is  increased,  whereas  weight 
is  lost  rapidly.  This  tetany  may  be  mitigated  or  even  abolished  by 
the  administration  of  sodium  bicarbonate,  alkalies,  calcium  salts ^  or 

1  Macallum  and  Voegtlin,  Johns  Hopkins  Univ.  Bull.,  1908. 


THE    THYROTD    AND    PARATHYROID    BODIES  963 

extracts  of  panithyrokl  tissue.  While  tlie  exact  sifrnificanoo  of  the 
symptoms  just  enumerated  is  not  known,  it  app(!ars  that  this  tetany 
is  the  outcome  of  some  profound  metabolic  chanjije  resulting  in  an  in- 
toxication. In  other  words,  in  the  absence  of  this  gland  certain  toxic 
substances  escape  reduction,  and  finally  attack  the  tissues.  This  ex- 
planation finds  substantiation  in  the  experiments  of  Macullum,^ 
which  show  that  bleeding  and  infusion  of  saline  solution  causes  the 
tetany  to  disappear,  and  that  the  injection  of  the  blood-serum  of 
animals  in  tetany  produces  these  symptoms  in  other  animals. 

The  specific  hypot  hesis  suggested  by  these  experiments,  is  that  the 
parathyroids  possess  the  power  of  detoxication  by  preventing  the  ac- 
cumulation of  certain  products  of  metabolism.  This  conclusion,  how- 
ever, is  not  fully  justified,  because  it  may  also  be  true  that  these  poisons 
are  not  formed  in  the  normal  l)ody  and  develop  only  in  the  absence  of 
the  parathyroids.  More  recently,  Paton^  has  brought  forth  the 
hypothesis  that  this  gland  regulates  the  metabolism  of  guanidin  and 
thereby  exerts  a  controlling  influence  upon  the  activity  of  the  muscles. 
Upon  its  removal,  the  guanidin  accumulates  and  gives  rise  to  a  fatal 
tetany.  This  contention  finds  support  in  the  fact  that  the  guanidin 
compounds  in  the  blood  and  urine  are  markedly  increased  after 
parathyroidectomy  and  are  also  present  in  excessive  amounts  in  the 
urine  of  children  suffering  from  idiopathic  tetany.  Furthermore,  it 
is  possible  to  evoke  the  symptoms  of  parathyreopriva  by  the  injec- 
tion of  salts  of  guanidin. 

B.  THE  THYMUS  GLAND 

Position  and  Structure  of  the  Thymus. — This  glandular  mass  is 
situated  in  the  anterosuperior  recess  of  the  mediastinal  space,  and 
covers  the  great  vessels.  By  origin  it  is  a  bilateral  organ,  consisting  of  a 
right  and  left  lobe  with  corresponding  prolongations  upward.  This 
division  is  also  in  evidence  in  the  adult  organ,  because  although  they 
overlap,  its  two  portions  may  be  separated  from  one  another  without 
much  difficulty  by  following  the  line  of  the  intervening  connective 
tissue.  The  size  of  this  organ  differs  greatly  in  accordance  with  the 
age  of  the  individual.  In  infants,  for  example,  its  average  weight  is  12 
grams,  at  puberty  35  grams,  at  sixty  years  less  than  15  grams,  and  at 
seventy  years  less  than  6  grams.  ^  When  fully  developed,  it  extends 
across  the  upper  portion  of  the  pericardial  sac  and  reaches  upward 
very  nearly  to  the  thyroid  gland. 

It  is  invested  by  a  thin  capsule  of  areolar  tissue  which  also  divides 
its  substance  into  lobules.  The  different  follicles  entering  into  the 
formation  of  the  latter,  are  made  up  of  a  central  portion  or  medulla  and 

1  Jour.  Exp.  Med.,  xi,  1909,  118,  also:  Jour,  of  Pharm.  and  Exp.  Therap.,  ii, 
1911,  421. 

2  Quart.  Jour,  of  Exp.  Physiol.,  x,  1917,  203. 

3  Hammar,  Archiv  fur  Anat.,  1906. 


964  THE    INTERNAL    SECRETIONS 

an  external  portion  or  cortex.  The  medulla  presents  itself  as  a  coarse 
network  of  connective  tissue  in  which  are  embedded  lymphoid  cells 
and  the  concentric  corpuscles  of  Hascall.  The  latter  are  of  endodermic 
origin,  and  have  been  formed  from  an  outgrowth  of  the  third  pharyngeal 
cleft.  The  former,  on  the  other  hand,  appear  to  be  of  mesodermic  ori- 
gin. The  cortex  is  made  up  of  a  similar  reticulum  of  connective  tissue, 
the  different  nodules  of  which  contain  numerous  lymphoid  cells. 
Although  derived  from  epithelial  tissue,  the  cortical  substance  even- 
tually acquires  the  general  characteristics  of  a  lymphatic  gland,  but 
this  transformation  is  not  complete,  because  it  contains  a  much  larger 
amount  of  nuclear  material  than  the  ordinarj^  glands  of  this  type. 
The  blood-supply  of  the  thymus  is  derived  from  the  internal  mammaiy, 
inferior  and  superior  thyroid,  subclavian  and  carotid  arteries. 

The  Function  of  the  Thymus. — ^^^lile  no  absolutelj'  definite 
statements  can  be  made  at  this  time  regarding  the  function  of  this 
gland,  it  is  ob^nous  that  it  exercises  a  metabohc  influence  which  attains 
its  greatest  importance  at  about  the  time  of  maturation.  In  support 
of  this  view  might  be  cited  the  involution  of  this  organ  after  puberty, 
and  secondlj',  the  fact  that  its  removal  gives  rise  to  a  more  rapid 
development  of  the  testes.^  Correspondingly,  the  removal  of  the 
latter  (castration)  delays  the  atrophy  of  the  former.^  It  is  surmised 
that  this  close  relationship  of  the  aforesaid  organs  is  brought  about 
wholly  b}'  chemical  means,  because  even  pieces  of  the  thjauus  of  rab- 
bits, when  transplanted  to  other  regions  of  the  body,  are  affected 
in    precisely   the  same  way  by  castration  and  sexual  stimulation.^ 

In  accordance  with  Klose  and  Vogt-  it  has  usually  been  supposed 
that  the  thymus  is  essential  to  Ufe  and  that  its  complete  removal 
proves  fatal  to  young  animals  within  a  verj^  short  time.  TMiile  these 
results  have  not  been  substantiated  by  the  work  of  Pappenheim, 
Howland  and  Vincent,^  it  appears  that  thymectomy  nevertheless 
produces  certain  metabohc  disturbances,  chief  among  which  are  a 
retardation  of  the  growth  of  the  bones,  mental  deterioration,  and  a 
■  tendency  to  adipositJ^  In  connection  with  this  point,  attention  should 
be  called  to  the  experiments  of  Gubernatsch  which  have  shown  that 
the  feeding  of  extract  of  thymus  to  young  tadpoles  stimulates  their 
growth,  but  retards  their  differentiation  or  metamorphosis.  Some 
authors,  in  fact,  recognize  a  condition  of  hyperthymusism  which  may 
be  a  comphcating  factor  in  Grave's  disease. 

C.  THE  LIVER 

The  Internal  Secretory  Power  of  the  Liver. — The  carbohydrates 
are  absorbed  in  largest  part  through  the  intestinal  radicles  of  the  portal 

1  Paton,  Jour,  of  Physiol.,  xxxii,  1905,  28,  and  xlii,  1911.  267. 

2  Goodall,  Jour,  of  Physiol.,  x.xxii.  1905.  191,  and  Pappenheimer,  Jour.  Exp. 
Med.,  xix,  1914,  319. 

'  Marine  and  Manley,  Jour.  Lab.  CUn.  Med.,  iii,  1917,  48. 
^  Klinik  and  Biol,  der  Thymusdr.  Tubingen,  1910. 
'  Ergebn.  der  Physiol.,  1911. 


THE    PANCREAS  966 

vein.  On  roacliinp;  tlio  liver,  sonic  of  the  rIucoso,  lovulose,  and  galac- 
tose is  taken  up  l)y  the  hepatic  celLs,  and  is  deposited  hen;  in  the  form 
of  a  colloidal  polysaccharide,  known  as  glycogen.  C^onsequcntly,  one 
of  the  functions  of  this  organ  is  to  store  and  to  hold  in  reserve  a  certain 
surplus  amount  of  cai'l)ohy(lratc  material  until  needed  by  the  other 
tissues.  But,  since  the  muscles  contain  almost  as  much  glycogen 
as  the  liver,  the  latter  cannot  be  said  to  be  the  only  place  in  which 
this  substance  is  deposited.  At  all  events,  the  liver  is  constantly 
called  upon  to  release  some  of  this  glycogen  and  more  particularly 
during  the  periods  intervening  })etween  meals,  when  practically  no 
sugar  is  absorbed.  Lastly,  this  oi-gan  possesses  the  power  of  forming 
dextrose  from  protein  material  and  even  from  many  partially  oxidized 
products  of  other  tissues.  This  synthesis  of  glycogen,  as  well  as  the 
reconversion  of  this  substance  into  sugar,  must  be  effected  by  means 
of  a  special  intrahepatic  principle.  Consequently,  it  may  be  said 
that  this  organ  furnishes  an  internal  secretory  product  which  has  to 
do  with  the  metabolism  of  the  carbohydrates. 

D.  THE  PANCREAS 

The  Removal  of  the  Pancreas. — Inasmuch  as  the  general  phy- 
siological anatomy  of  the  pancreas  has  been  discussed  at  some  length 
in  connection  with  its  external  secretion,  it  may  suffice  at  this  time  to 
state  that  this  organ  also  contains  numerous  colonies  of  cells  which  have 
been  named,  after  their  discoverer,  the  islands  of  Langerhans  (1869). 
These  groups  of  cells  are  tugged  away  in  between  the  different  acini 
and  are  composed  of  polygonal  cells  possessing  poorly  defined  bound- 
aries, large  round  nuclei,  and  relatively  few  and  small  granules.  They 
are  copiously  supplied  with  blood  from  an  interstitial  system  of  cap- 
illaries. Bensley^  has  proved  by  the  method  of  intra vitam  staining 
that  these  structures  are  permanent  and  should  not  be  regarded  as 
developing  reserve  cells  of  the  acini. 

It  was  CI.  Bernard^  who  first  called  attention  to  the  fact  that  the 
occlusion  of  the  duct  of  Wirsung  produces  a  complete  atrophy  of  the 
acini  of  the  pancreas,  but  does  not  destroy  the  islets  of  Langerhans. 
In  1889,  Mering  and  Minkowski^  proved  that  the  total  extirpation 
of  this  organ  gives  rise  not  only  to  digestive  disorders,  owing  to  the 
loss  of  the  pancreatic  juice,  but  also  to  a  complex  of  symptoms  com- 
monly associated  with  the  disease,  called  diabetes  mellitus.  The 
animal  shows  a  hyperglycemia,  glycosuria,  polyuria,  poliphagia,  a 
loss  of  weight,  an  abnormal  thirst  and  hunger,  emaciation  and  muscu- 
lar weakness.  This  disease  terminates  fatally  in  the  course  of  two  to 
four  weeks.     Contrary  to  the  effect  of  total  extirpation,  the  removal 

*  Harvey  Lectures,  New  York,  x,  1915. 

-  Sebolew,  Virchow's  Archiv,  clxviii,  1902,  91,  and  Homans,  Journ.  of  Med. 
Research,  1914. 

'  Archiv  fiir  exp.  Path,  und  Pharm.,  xxi,  1893,  85. 


966  THE    INTERNAL    SECRETIONS 

of  only  a  part  of  this  organ  does  not  produce  these  symptoms,  nor  do 
they  appear  if  a  portion  of  its  tissue  is  transplanted.  The  latter 
procedure  usually  consists  in  grafting  its  processus  uncinatus  and  cor- 
responding blood-vessels  under  the  skin  of  the  abdomen.  It  has  also 
been  established  that  the  ligation  of  the  ducts  of  the  pancreas  does  not 
produce  a  permanent  glycosuria,  but  only  those  symptoms  which  are 
commonly  associated  with  a  loss  of  the  pancreatic  juice. 

The  Function  of  the  Internal  Secretion  of  the  Pancreas. — The 
fact  to  be  derived  from  the  preceding  data,  is  that,  in  addition  to  its 
digestive  juice,  the  pancreas  also  produces  an  internal  secretion  which 
is  absolutely  essential  to  the  life  of  the  animal.  While  the  evidence  is 
not  absolutely  conclusive,  it  is  surmised  that  this  internal  secretion 
arises  in  the  cells  of  the  islets  of  Langerhans.  This  assumption  is 
strengthened  somewhat  by  the  statements  of  Opie^  and  others  that 
these  cells  show  signs  of  hyaline  degeneration  and  atrophy  in  persons 
who  have  died  of  diabetes  mellitus.  The  correctness  of  this  observa- 
tion, however,  has  recently  been  questioned. ^  Nothing  definite  is 
known  regarding  the  cause  of  this  disease,  although  it  is  supposed  that 
it  develops  in  consequence  of  a  disturbance  of  the  carbohydrate 
metabolism.  Regarded  from  a  very  general  standpoint,  the  conditions 
leading  to  glycosuria,  may  be  classified  under  the  following  headings: 

(a)  Alimentary;  too  copious  an  absorption  of  sugar  is  frequently  followed  by 
a  temporary  excretion  of  this  substance  in  the  urine.  This  condition  is  known  as 
alimentary  or  physiological  glycosuria.  It  subsides  as  soon  as  the  body  has  suc- 
ceeded in  ridding  itself  of  the  excessive  amounts  of  sugar  absorbed. 

{b)  Pancreatic;  a  disorder  in  the  internal  secretory  power  of  the  pancreas  is  the 
cause  of  this  form  of  glycosuria. 

(c)  Hepatic;  the  cells  of  the  liver  do  not  exercise  their  storative  functions 
properly,  and  allow  too  large  an  amount  of  sugar  to  escape  into  the  blood. 

(d)  Oxidative;  the  cells  of  the  tissues  are  unable  to  oxidize  the  sugar,  because 
they  lack  the  agent  which  is  required  to  accomplish  this  reduction.  The  latter 
may  be  conveyed  to  them  from  the  pancreas  or  may  be  a  product  of  their  own. 

(e)  Renal;  the  cells  of  the  kidney  have  lost  their  relative  impermeability  and 
allow  the  sugar  of  the  blood  to  pass  more  readily  through  them. 

Since  in  the  present  instance  we  are  solely  concerned  with  the  pan- 
creatic type  of  diabetes,  this  problem  may  be  restricted  in  the  following 
way:  The  pancreas  furnishes  an  active  principle,  possibly  an  enzyme, 
which  aids  in  the  hydrolysis  or  oxidation  of  the  sugar  in  the  tissues. 
In  the  absence  of  this  agent,  this  process  remains  incomplete  and 
the  sugar  escapes  into  the  urine.  In  this  case,  therefore,  the  internal 
secretion  of  the  pancreas  acts  in  the  manner  of  a  hormone,  i.e.,  as 
a  stimulus  to  cellular  activity.  Another  view  is  that  the  pancreas 
furnishes  an  active  principle  which  regulates  the  sugar  output  of  the 
liver.  In  the  absence  of  this  agent,  the  cells  of  the  liver  convert 
their  glycogen  too  rapidly,  thereby  increasing  the  sugar  content  of 
the  blood  and  producing  a  hyperglycemia  which  is  soon  followed  by  a 

1  Jour.  Exp.  Med.,  v,  1901,  397. 

2  Vincent  and  Thompson,  Jour,  of  Physiol.,  xxxiv,  1906. 


THE    ADRENAL   BODIES  967 

glycosuria.  In  this  case,  therefore,  the  internal  secretion  of  the  pan- 
creas acts  as  a  chalone,  because  it  checks  the  activities  of  the  hepatic 
cells.  The  weiji;ht  of  cv^ideiicc",  however,  seems  to  li(!  with  the  first 
theory  which  holds  (hat  this  internal  secretion  facilitates  the  reduction 
of  the  sugar  by  t  h(>  tissues.  Thus,  it  has  been  found  by  Clark  that  the 
perfusion  of  the  pancreas  with  solutions  containing  dextrose,  causes 
this  substance  to  be  changed  into  some  form  of  polysaccharide.  On 
allowing  this  condensed  dextrose  to  circulate  through  the  tissues,  it 
undergoes  a  further  change  into  a  carbohydrate  which  is  easily  utilized 
by  these  cells.  Thus,  it  is  claimed  by  Woodyatt^  that  sugar  exists 
in  the  blood  in  some  chemical  combination  which  behaves  like  a 
colloid.  The  substance  which  combines  with  dextrose  to  form  this 
compound,  is  closely  related  to  the  internal  secretion  of  the  pancreas. 
The  Internal  Secretion  of  the  Gastric  and  Intestinal  Mucosa. — 
In  elaboration  of  the  preliminary  experiments  of  CI.  Bernard, 
Popielski,  Wertheim  and  Lepage,  it  was  found  by  Bayliss  and  Starling 
that  the  mucous  membrane  of  the  duodenum  contains  a  hormone, 
known  as  secretin,  which  is  liberated  whenever  the  reaction  of  the 
adjoining  medium  is  changed  to  acid.  Upon  its  absorption  by  the 
blood,  this  agent  is  carried  to  the  pancreas,  liver  and  intestine,  where  it 
excites  a  flow  of  the  corresponding  secretions.  A  similar  hormone, 
called  gastrin,  has  been  isolated  by  Edkins  from  the  mucous  mem- 
brane of  the  pylorus.     It  causes  a  secretion  of  gastric  juice. 


CHAPTER  LXXXII 

THE    ADRENAL    BODIES,    HYPOPHYSIS,    PINEAL    GLAND, 
TESTES  AND  OVARIES 

E.    THE  ADRENAL  BODIES  OR  SUPRARENAL  CAPSULES 

The  Position  and  Structure  of  the  Adrenals.  ^ — These  glands  are 
situated  in  the  epigastric  region,  one  on  each  side  of  the  spine  and  in 
the  immediate  vicinity  of  the  upper  pole  of  the  kidney.  They  differ 
somewhat  in  their  size,  shape  and  position.  The  right  organ  is  affixed 
to  the  inferior  vena  cava  in  close  proximity  to  the  orifice  of  the  right 
suprarenal  vein,  while  the  left  organ  lies  in  relation  with  the  left 
suprarenal  vein,  but  does  not  come  in  actual  contact  with  the  cava.^ 
Their  arterial  supply  is  derived  from  three  sources,  namely,  from  the 

1  Jour.  Am.  Med.  Assoc,  1915. 

2  The  suprarenal  capsules  were  first  recognized  by  Bartholomeus  Eustachius 
Sanctoseverinatus  in  1563.  An  adequate  description  of  them  was  given  by  Win- 
slow  in  1756.  Their  structural  peculiarities  have  been  dealt  with  by  Meckel 
(1806),  Ecker  (1846),  Leydig  (1851)  and  Kolliker  (1854).  ^ 

^  Ferguson,  Am.  Jour,  of  Anatomy,  v,  1905. 


968 


THE    IXTERXAL    SECRETIONS 


aorta  by  two  or  three  small  branches,  and  from  the  phrenic  and  renal 
arteries.^  It  is  also  of  importance  to  remember  that  each  gland 
rests  upon  a  ramification  of  sj-mpathetic  fibers  which  is  known  as  the 
suprarenal  plexus,  and  which  communicates  centrally  by  way  of  the 
greater  and  lesser  splanchnic  nerves  (Fig.  226)  with  the  s\Tnpathetic 
gangha  of  the  thorax  and  lumbar  region.  Peripherally,  each  supra- 
renal plexus  is  connected  with  the  mesenteric  and  celiac  ganglia  of 
the  solar  plexus. 

The  right  gland  has  a  flattened,  triangular  outline,  while  the  left  is  crescentic, 
its  concavity  being  directed  toward  the  neighboring  kidney.  In  man,  each  gland 
measures  about  3  cm.  from  side  to  side,  3-5  cm.  from  above  downward  and  -i-6 
mm.  in  thickness.      Their  weight  varies  between  -4  and  7  grams,  the  left  one  being 


Fig.  507. — Diagram  to  Illustrate  the  Position  of  the  Adrenal  Glavds  (Rabbit). 
K,  kidneys;  T'.  ureters;  RV.  renal  veins;  RA,  renal  arterie.s;  JC.  inferior  vena  cava; 
A,  abdominal  aorta;  -S',  adrenal  glands;  SU ,  suprarenal  veins.  In  man,  the  two  kidneys 
lie  ver>-  nearly  in  the  same  horizontal  plane;  in  fact,  the  right  organ  frequently  below 
the  left. 


slightly  heavier  than  the  right.  When  cut  into,  each  gland  exhibits  an  outer 
cortical  and  an  inner  inedidlary  region.  The  former  is  divided  into  compartments 
by  a  fibrous  stroma  derived  from  the  outer  fibrous  investment.  These  spaces  are 
occupied  by  numerous  columns  of  intercommunicating  cells  which  are  roughly 
arranged  in  the  form  of  a  reticular  and  glomerular  zone.  The  yellowish  globules 
Oipoids)  contained  in  these  cells,  are  responsible  for  the  peculiar  yellowish-pink 
color  of  the  entire  gland.  The  medulla  is  perv^aded  by  a  stroma,  enclosing  groups 
of  granular  cells,  which  on  treatment  ^-ith  chromic  acid  acquire  a  yellowish  brown 
color.  On  account  of  their  power  of  reducing  this  substance,  they  are  commonly 
designated  as  chromophil  or  chromaflfine  cells.  We  also  find  here  numerous  nerve 
cells,  some  smooth  muscle  tissue,  and  large  venous  capillaries  supported  by  fibrous 
tissue.  These  structural  differences  are  in  complete  agreement  with  the  develop- 
ment of  this  organ,  because  while  the  cortex  is  derived  from  that  part  of  the 
mesoblast  which  gives  rise  to  the  mesonephros.  the  medulla  is  formed  from  an 
out2ro\\-th  of  the  sympathetic  system.  Besides,  these  two  con.stituents  of  the 
adrenal  body  remain  absolutely  separate  in  some  of  the  lower  vertebrates,  the 

'  Gerard,  Jour,  de  I'anat.  et  de  la  physiol.,  1913- 


THE    ADRENAL   BODIES 


969 


medullary  substances  appearinp;  in  them  in  the  form  of  isolated  globular  masses 
along  the  course  of  the  si)iiial  nerves.  A  few  separate  chroinafhne  Ixxlies,  similar 
to  or  identical  witli  the  medulla  of  the  adrenal  !:;land,  are  also  found  in  almost  all 
the  higher  animals. 

Removal  of  the  Adrenal  Glands. — The  function  of  the  suprarenal 
glands  remained  a  matter  of  speculation  until  1853,  when  Thomas 
Addison  called  attention  to  the  fact  that  the  degeneration  of  these 
bodies  is  associated  with  a  disease 
which  has  since  been  named  after  him. 
It  is  almost  invariably  fatal  and  is 
characterized  by  a  progressive  idio- 
pathic anemia,  digestive  disoi-ders, 
diarrhea,  muscular  weakness,  tremors, 
convulsions,  apathy,  and  a  bronzing 
of  the  skin.  A  few  years  later  Brown- 
S^quard^  showed  that  these  symp- 
toms also  develop  in  animals  after  the 
complete  removal  of  the  adrenals,  t': 
Death  then  results  within  two  or 
three  days  after  the  operation.  These 
results  were  proved  to  be  correct  by  T 
Nothnagel,-  Tizzoni,^  and  others.  In 
addition.  Stilling^  established  the  fact 
that  the  extirpation  of  only  one  of 
them  does  not  prove  fatal,  but  is 
compensated  for  by  an  enlargement 
of  the  opposite  organ.  The  same 
favorable  results  may  be  obtained  by 
leaving  a  piece  of  one  organ  in  situ 
or  by  transplanting  it  elsewhere  in 
the  body.  Subsequent  to  the  unsuc- 
cessful experiments  of  Canalis  (1887) 
and  Imbort  (1899),  it  was  shown  by 
Haberer^and  StoerkHhat  these  glands 
may  also  be  transplanted  within  the  Cortex  of  Supraeenal  of  Dog.  Mag- 
substance  of  the  kidney,  but  only  if    nified  about  150  diameters. 

.,..,11  1        .  j_    •     .      i-         1  a.   Fibrous    capsule;  o,    zona  glo- 

their  blood-supply  is  not  mteriered  merulosa;  c,  zona  fasciculata;  d,  zona 
with.       In     like    manner,     BiedF    sue-     reticularis.     {Bohn  and  v.  Davidoff.) 

ceeded  in  growing  them  outside  the 

peritoneum.     In  all  these  cases,  these  transplants  first  exhibited  an 

initial  retrogression  and  necrosis  which  was  followed  after  about  five 

1  Compt.  rend.,  1857. 

2  Zeitschr.  fiir  klin.  Med.,  i,  1879,  77,  and  Allg.  Med.  Zeitschr.,  1890. 
^  Ziegler's  Beitrage,  1889. 

4  Rev.  med.,  1888,  and  Ziegler's  Beitrage,  1905. 
*  Wiener,  klin.  Wochenschr.,  1908. 
«  Archiv  fiir  klin.  Chir.,  1908. 
^  Pfliiger's  Archiv,  Ixvii,  1897. 


.^a^ 


Fig.    508. — Vertical    Section  of 


970  THE    INTERNAL    SECRETIONS 

months  by  an  active  proliferation.  In  tliis  connection,  it  should  also 
be  mentioned  that  the  results  obtained  by  the  feeding  of  extract  of 
adrenal  gland  to  animals  whose  adrenals  had  been  removed,  have 
not  been  encouraging.  Moreover,  in  only  a  few  cases  has  this  type 
of  organotherapy  been  of  any  use  in  relieving  the  symptoms  of  Addi- 
son's disease. 

The  General  Function  of  the  Adrenal  Glands. — While  the  effects 
of  total  and  partial  extirpation  of  the  adrenals  clearly  proved  that 
these  organs  furnish  an  active  principle  which  is  absolutely  essential 
to  life,  the  nature  of  this  internal  agent  was  not  revealed  until  the 
time  of  Oliver  and  Schafer.^  These  investigators  made  an  extract 
of  this  gland  and  injected  it  into  the  venous  blood-stream.  A  rise 
in  blood-pressure  invariably  resulted  which  was  correctly  referred  by 
them  to  a  constriction  of  the  blood-vessels.  Further  experimentation 
then  showed  that  this  vasoconstrictor  agent  is  a  product  of  the  medulla 
and  not  of  the  cortex  of  this  gland.  Nothing  definite,  however, 
could  be  learned  regarding  the  function  of  the  latter,  although  it  was 
surmised  that  its  loss  gives  rise  to  a  decided  muscular  weakness  (as- 
thenia) of  the  skeletal  muscles,  coma,  and  convulsions.  The  evidence 
which  has  been  presented  in  favor  of  this  view,  is  chiefly  indirect 
in  its  character  and  is  based  upon  the  following  data: 

(a)  The  symptoms  just  cited  cannot  be  mitigated  by  the  repeated  or  continuous 
administration  of  extracts  of  the  medulla,  in  the  form  of  epinephrin  or  adrenalin. 

(b)  It  has  been  shown  by  Stewart  that  the  discharge  of  epinephrin  into  the 
circulation  ceases  immediately  after  the  removal  of  one  adrenal  body  and  the 
denerv^ation  of  the  other.  This  procedure,  however,  does  not  prove  fatal  to  the 
animal. 

(c)  Xo  beneficial  results  have  been  obtained  so  far  by  treating  Addison's 
disease  with  adrenalin  which  is  a  product  of  the  medulla. 

(d)  Those  animals  which  are  in  possession  of  "accessory"  adrenals  in  the  form 
of  separate  chromafiin-bodies  (rabbits),  do  not  die  after  the  removal  of  the  adrenal 
glands,  and 

(e)  It  has  been  found  that  transplanted  adrenals  exhibit  a  degeneration  of  their 
medulla  and  a  proliferation  of  their  cortex. 

It  will  be  remembered  that  these  animals  develop  no  untoward  symp- 
toms. Thus,  it  cannot  be  doubted  that  the  internal  agent  of  the  cor- 
tex is  different  from  that  of  the  medulla.  While  the  former  furnishes 
a  still  obscure  product,  the  absence  of  which  gives  rise  to  the  grave 
symptoms  mentioned  above,  the  latter  gives  rise  to  epinephrin. ^ 
Epinephrin. — The  extract  of  adrenal  gland  employed  by  Oliver  and 
Schafer,^  was  obtained  by  simply  lacerating  and  pounding  the  adrenal 
tissue  in  a  mortar  under  a  0.7  per  cent,  solution  of  sodium  chlorid.^ 

Uour.  of  Physiol.,  xxviii,  1895,  230. 

2  Vincent,  Endocrinology,  i,  1917,  1-10.  and  Schafer,  The  Endocrine  Organs-, 
London,  1916. 

^  A  year  later  Cybulski  and  Szymonowicz  published  the  results  of  a  series  of 
independent  experiments  of  similar  nature    (Pro.  Acad,  of  Krackau,  1895). 

■*  In  1856  Vulpian  isolated  a  substance  from  the  adrenal  gland  which  showed 
remarkable  color  reactions  (Compt.  rcn.l..  xliii.  1856). 


THE    ADRENAL  BODIES  971 

The  filtered  extract  was  then  injected  intravenously,  only  a  few  drops 
being  required  to  evoke  a  marked  rise  in  blood  pressure.  Some  years 
later  AbeP  succeeded  in  isolating  this  active  agent  by  extracting  the 
gland  with  weak  acid  and  benzojdating  it,  but  the  substance  which  he 
obtained  was  not  the  pure  active  principle  but  a  benzoylated  compound 
of  it.  He  designated  this  body  as  epinephrin.  Later  on  Aldrich^ 
and  Takamine^  obtained  its  free  base,  and  called  it  adrenalin.  Since 
then  physiological  chemists  have  determined  its  constitution  as: 

HO 


H0<  >  -  CH(OH)  -  CH2NHCH, 


It  possesses  an  asymmetric  carbon  atom  and,  therefore,  may  be  either 
levo-  or  dextro-rotatory.  Both  these  forms  have  been  prepared  syn- 
thetically.    Stolz  and  Dakin  give  its  formula  as  C9H19NO3. 

Under  normal  conditions  this  agent  is  transferred  from  the  medul- 
lary substances  into  the  suprarenal  vein,  whence  it  reaches  the 
general  circulatory  system  by  way  of  the  inferior  vena  cava.  The 
active  principle  thus  normally  diverted  into  the  blood-stream,  is  known 
as  adrenin.  It  need  scarcely  be  mentioned  that  we  may  also  em- 
ploy the  blood  of  the  suprarenal  vein  in  order  to  produce  a  rise  in 
blood  pressure,  but  it  should  be  remembered  that  adrenin  is  an  unstable 
body  and  decomposes  very  rapidly.  This  is  the  reason  why  the  reac- 
tion produced  by  it  cannot  be  long  continued.  Even  adrenalin  is  an 
unstable  and  weak  base,  but  is  more  stable  as  a  dry,  free  base  or  as 
the  hydrochlorid,  in  which  form  it  may  be  kept  for  some  time  unless 
unduly  exposed  to  the  Ught  and  air.  The  amount  of  adrenin  present 
in  the  gland  may  be  estimated  by  colorimetry  as  well  as  by  the  ampli- 
tude of  the  circulatory  reaction  produced  by  it,  i.e.,  by  physiological 
means.*  Its  free  base  is  extremely  potent;  as  little  as  0.000002 
gram  sufficing  to  evoke  a  marked  change  in  the  blood  pressure.  The 
suprarenals  of  human  adults  contain  1.0  per  cent,  of  adrenin,  those  of 
the  cat  0.15  per  cent.,  and  those  of  rabbits,  dogs,  and  monkeys  from 
0.2  to  0.3  per  cent.  In  this  connection,  it  is  also  of  interest  to  note 
that  the  parotid  gland  of  the  Jamaican  toad  secretes  a  similar  principle 
in  amounts  equalling  5.0  per  cent. 

The  Action  of  Epinephrin  upon  the  Circulation. — The  most  charac- 
teristic action  of  extracts  of  the  adrenal  bodies  or  of  the  commercial 
preparation  adrenalin  is  a  rise  in  blood  pressure  and  a  slowing  of  the 
hear  t  beat.  But  since  these  effects  are  usually  obtained  by  injecting  the 
diluted  adrenalin  into  the  venous  blood-stream,  a  certain  time  must 
elapse  before  it  can  reach  the  arterial  system  to  activate  the  vasocon- 

1  Bull.  Johns  Hopkins  Univ.,  1898. 

2  Am.  Jour,  of  Physiol.,  v,  1901,  457. 
» Jour,  of  Pharm.,  l.x.xiii,  1901,  523. 

*  Folin,  Cannon  and  Denis,  Jour.  Biol.  Chem.,  xiii,  1912,  477;  Seidell,  ibid., 
XV,  1913,  197,  and  Steward,  Jour.  Exp.  Med.,  xiv,  1911,  377. 


972  THE    INTERNAL   SECRETIONS 

stricter  mechanism.  This  is  also  true  of  adrenin,  because  inasmuc^h  as 
the  normal  glands  discharge  their  product  into  the  suprarenal  veins, 
it  must  first  be  carried  through  the  heart  into  the  arteries.  With  a 
normally  active  circulation  this  requires  from  12  to  14  seconds.  At 
the  end  of  this  period  of  time,  the  blood  pressure  rises  rather  abruptly, 
but  declines  very  soon  until  its  normal  value  has  again  been  estab- 
lished. The  amplityde  of  this  reaction  depends,  of  course,  upon  the 
potency  and  quantity  of  the  adrenalin.  Upon  the  heart,  this  agent 
acts  in  two  ways,  namely  (a)  by  lessening  the  frequency  of  this  organ 
through  vagus-inhibition,  and  (6)  by  augmenting  its  force  of  con- 
traction by  a  direct  influence  upon  the  cardiac  musculature.  Con- 
sequently, the  division  of  the  vagi  nerves  must  augment  the  rise  in 
blood  pressure,  because  it  prevents  henceforth  the  inhibitory  dis- 
charges of  the  center  from  reaching  the  heart.  It  should  be  emphasized, 
however,  that  the  adrenalin  does  not  stimulate  the  cardio-inhibitor 
center  directly,  but  in  an  indirect  way  through  its  effect  upon  the  blood 
pressure.  As  has  been  pointed  out  in  one  of  the  preceding  chapters, 
a  high  blood  pressure  invariably  elicits  a  reflex  which  slows  the  heart, 
its  cause  being  resident  in  the  distention  of  the  arteries,  chiefly  of 
the  root  of  the  aorta. 

Regarding  the  nature  of  this  reaction,  it  may  be  stated  that  the 
adrenalin  constricts  the  arteries,  and  especially  the  arterioles,  thereby 
preventing  normal  amounts  of  arterial  blood  from  escaping  into  the 
capillaries.  Its  action,  therefore,  is  to  increase  the  peripheral  resistance 
by  lessening  the  size  of  the  arterio-capillary  outlet.  At  this  point 
of  the  vascular  system  two  elements  are  present,  namely  the  smooth 
muscle  cells  and  the  terminals  of  the  vasomotor  nerves.  Where 
then  is  the  point  of  attack  of  the  adrenalin?  Since  this  rise  in  blood- 
pressure  may  also  be  produced  after  the  destruction  of  the  cord  and 
sympathetic  ganglia  and  even  after  the  completion  of  secondary 
degeneration  of  the  postganglionic  fibers,  it  cannot  justly  be  regarded 
as  a  nervous  reaction.  Moreover,  the  evidence  so  far  presented  tends 
to  show  that  it  does  not  affect  the  contractile  elements  of  the  smooth 
muscle  cells  directly,  but  some  substance  interposed  between  the  latter 
and  the  terminals  of  the  nerve.  In  accordance  with  Langley  and 
Elliott,  it  must  be  concluded  that  this  structure  is  the  myoneural 
junction  which  is  composed  of  receptor  substance,  i.e.,  of  a  type  of 
neuroplasm  somewhat  distinct  from  ordinary  nerve  tissue.  Adrena- 
lin, therefore,  acts  upon  the  myoneural  connection  between  the  sym- 
pathetic nerve  fibers  and  the  muscle  cells. 

At  the  hand  of  this  fact,  it  will  now  be  seen  that  the  adrenin  dis- 
charged by  the  adrenal  bodies,  must  exercise  a  similar  function.  It  is 
poured  out  as  a  rule  in  insignificant  amounts  and  aids  in  keeping 
the  vascular  system  in  a  semi-constricted  condition  i.e.,  in  a  state  of 
tonus.  Moreover,  in  consequence  of  definite  stimuli,  larger  amounts 
may  be  discharged  at  any  time  which  actually  constrict  the  blood- 
vessels and  give  rise  to  a  temporary  increase  in  blood  pressure.     This 


THE    ADRENAL   BODIES  973 

statement,  however,  is  not  intendcul  to  imply  that  the  tonus  of  the 
vascuhir  system  depends  exehisively  ujion  the  presenee  of  ach-enin  in 
the  blood-str(>;im.  Siieh  an  assertion  cannot  be  correct,  because  the 
walls  of  the  blood-vessels  are  already  tonically  set  by  virtue  of  the  tonic- 
ity resident  in  all  living  cells,  and  all  the  adrenin  can  do  is  to  vary 
their  tonus.  The  fact  that  adrenin  is  lil)erated  at  a  definite  rate  may 
be  ]M-oved  by  ai)plyinf2;  a  temporary  ligature  to  the  suprarenal  vein. 
Very  shortly  after  this  obstruction  to  the  venous  return  has  been  re- 
moved, the  blood  pressure  invariably  shows  an  abrupt  rise  which 
indicates  that  a  certain  amount  of  the  accumulated  adrenin  has 
reached  the  general  circulator}^  sj'stem.  Verj^  similar  results  may  be 
obtained  by  temporarily  ])locking  the  inferior  vena  cava  centrally  to 
the  orifices  of  the  suprarenal  veins.  Whenever  the  blood  is  then 
allowed  to  escape  from  this  pocket,  the  arterial  pressure  rises,  again 
proving  that  this  stagnated  cava  blood  has  been  charged  with  adrenin. 
Under  ordinary  conditions,  however,  the  amount  of  this  "spontane- 
ously" Uberated  adrenin  is  ver}^  small.  Thus,  Stewart  and  Rogoff^ 
estimate  it  in  cats  at  only  0.001  gram  per  minute.  If  this  amount  is 
added  to  the  blood  of  the  general  circuits,  it  will  be  seen  that  its  con- 
centration must  be  diminished  so  as  to  render  it  practically  ineffective. 
Actual  changes  in  the  circulation,  therefore,  can  only  occur  when  its 
discharge  is  increased  by  stimulation. 

The  adrenahn  or  adrenin  introduced  into  the  circulation,  is 
oxidized  very  soon  after  it  has  performed  its  temporary  excitatory 
action.  This  instability  also  accounts  for  its  rapid  disappearance  from 
food,  so  that  perfectly  enormous  doses  of  it  must  be  administered  by 
mouth  before  it  can  produce  its  effect  upon  the  blood  pressure.  Certain 
substances,  however,  have  been  isolated  from  the  amino-acids  by  a 
process  of  decarboxjdation  which,  although  similar  in  their  composi- 
tion to  adrenaUn,  possess  a  much  greater  stability.  Some  of  these 
form  the  active  principle  of  ergot.  Adrenalin  applied  locally  to 
open  surfaces  constricts  the  blood-vessels  and  may  therefore  be  em- 
ployed as  a  means  to  stop  excessive  hemorrhagic  oozing.  When  added 
to  solutions  of  sodium  chlorid  used  for  purposes  of  infusion,  it  acts 
as  a  vasoconstrictor  agent,  thereby  raising  the  blood  pressure  and  pro- 
ducing a  stimulation  of  the  heart  by  establishing  a  much  greater  per- 
ipheral resistance  than  could  be  obtained  with  the  sodium  chlorid 
alone. 

The  Innervation  of  the  Adrenal  Bodies. — The  activity  of  the 
adrenal  glands,  at  least  of  their  medullary  portions,  is  controlled  by 
nerve  fibers  which  are  derived  from  the  greater  splanchnic  nerves. 
Thus,  BiedP  and  Dreyer^  have  shown  that  the  stimulation  of  this 
nerve,  or  of  its  distal  end,  gives  rise  to  a  copious  discharge  of  adrenin 
which,   upon  reaching   the  distant  arterial  system,   constricts  these 

1  Jour.  Exp.  Med.,  xxiv,  1916,  709. 

2  Pfliiger's  Archiv,  Ixvii,  1897,  443. 

3  Am.  Jour,  of  Physiol.,  ii,  1899,  283. 


974  THE  INTERNAL  SECRETIONS 

blood-vessels  and  produces  a  second  rise  in  pressure.  Attention  has 
already  been  called  to  the  fact  that  the  stimulation  of  the  aforesaid 
nerve  evokes  a  rise  in  the  arterial  pressure  which  really  consists  of  two 
parts,  the  first  elevation  being  caused  by  the  direct  constriction  of  the 
blood-vessels  of  the  splanchnic  organs,  and  the  second  by  the  constric- 
tion of  the  blood-vessels  of  the  general  circuits  in  consequence  of  the 
delayed  entrance  of  adrenin. 

The  fact  that  the  adrenal  bodies  may  be  influenced  reflexly,  has 
given  rise  to  the  assumption  that  this  mechanism  is  held  in  reserve 
to  be  activated  at  irregular  intervals  by  afferent  stimuli  which  find 
their  origin  in  different  parts  of  the  body.  Even  emotions  are  said  to 
give  rise  to  a  discharge  of  adrenin  which  then  evokes  the  peculiar 
vascular  reactions  and  sensations  usually  experienced  during  anger  and 
fright.^  In  continuance  of  this  line  of  thought  it  is  generally  believed 
that  the  condition  of  hypertension,  which  is  developed  in  nephritis, 
is  the  direct  outcome  of  a  continuous  liberation  of  adrenin  and  that 
this  agent,  owing  to  its  power  of  mobilizing  sugar,  must  be  instrumental 
in  the  production  of  hyperglycemia  and  glycosuria.  All  these  and 
similar  statements,  endeavoring  to  equip  the  adrenals  with  emergency 
functions  of  this  kind,  should  be  received  with  scepticism,  because 
they  are  still  lacking  a  definite  experimental  basis.  Some  writers, 
for  example,  are  of  the  opinion  that  emotional  hyperglycemia  may  be 
produced  so  easily  in  animals  that  it  is  difficult  to  ascertain  the  normal 
sugar  content  of  their  blood  unless  precautions  are  taken  to  shield 
them  against  excitement. ^  Others,  again,  hold  that  a  real  emotional 
glycosuria  does  not  exist.  ^  Besides,  Stewart  and  Rogoff^  have  not 
been  able  to  demonstrate  any  increase  in  the  percentage  of  sugar  in 
the  blood  of  normal  cats  which  could  justly  be  referred  to  emotional 
states.  Nor  have  these  authors  been  able  to  detect  any  difference  in  this 
respect  between  normal  cats  and  cats  deprived  of  their  adrenals  by 
enucleation  or  nerve-section.  Accordingly,  it  must  be  concluded  that 
the  mobilization  of  sugar  occurring  during  experimental  hyperglycemia 
is  not  evoked  by  adrenin,  nor  is  the  so-called  emotional  hyperglycemia 
a  common  phenomenon.  This  diversity  of  opinion  demands  that  care 
be  exercised  in  attributing  to  the  adrenal  bodies  an  array  of  functions 
which  in  reality  are  mere  conjectures. 

Other  Actions  of  Epinephrin. — Since  epinephrin  serves  more  es- 
pecially as  a  stimulant  of  the  sympathetic  division  of  the  autonomic 
nervous  system  (Langley),  it  may  be  conjectured  that  its  action  is  a 
very  general  one,  involving  all  the  smooth  muscle  tissue  and  gland 
tissue  ordinarily  under  the  control  of  these  elements.  Moreover, 
since  it  acts  as  a  general  excitant  of  the  sympathetic  system,  the  effect 

1  Cannon,  Am.  Jour,  of  Psych.,  xxv,  1914,  256. 

2  Schaffer,  Jour.  Biol.  Chem.,  xix,  1914,  297. 

3  Ross  and  McGuigan,  ibid.,  xxii,  1915,  407. 
*  Am.  Jour,  of  Physiol.,  xlvi,  1917,  543. 


THE    ADRENAL   BODIES  975 

produced  by  it  may  be  either  an  augmentation  or  an  inhibition  in 
accordance  with  the  structural  characteristics  of  the  effector  so  affected. 
This  also  implies  that  the  reaction  thus  ensuing,  is  practically  identical 
with  that  induced  by  the  stinmlation  of  the  sympathetic  fibers  them- 
selves. As  has  been  stated  above,  the  action  of  adrenalin  is  made 
possible  through  the  intervention  of  a  special  receptor  substance. 
Thus,  Meltzor^  has  shown  that  adrenalin  administered  intravenously, 
dilates  the  pupil,  while  its  direct  instillation  into  the  conjunctival  sac 
is  not  followed  by  this  reaction  unless  the  superior  cervical  ganglion 
has  been  removed  beforehand.  This  agent  may  also  be  employed  to 
determine  the  constrictor  power  of  the  different  blood-vessels.  In 
illustration  of  this  statement  it  might  be  mentioned  that  its  injection 
into  the  cerebral  circulation  gives  a  positive  reaction,  while  its  injection 
into  the  pulmonary  circuit  does  not.  The  inference  to  be  derived  from 
these  tests,  is  that  the  blood-vessels  of  the  brain  are  equipped  with  a 
vasomotor  mechanism,  while  those  of  the  lungs  are  not. 

Inasmuch  as  the  smooth  muscle  tissue  of  the  walls  of  the  intestine 
is  supplied  with  inhibitorj^  fibers  from  the  sj'^mpathetic  division  of  the 
autonomic  system,  adrenalin  must  cause  a  loss  of  its  tonus  and  a 
disappearance  of  intestinal  peristalsis.  A  similar  effect  is  produced 
by  it  upon  the  walls  of  the  stomach,  gall-bladder  and  urinarj'  bladder. 
In  the  case  of  the  pregnant  uterus  of  the  cat,  it  gives  rise  to  a  contrac- 
tion, but  to  a  relaxation  in  the  non-pregnant  organ.  The  vas  deferens 
and  seminal  vesicles  are  contracted,  while  the  plain  musculature  of  the 
bronchioles  is  relaxed.  It  also  possesses  a  relaxing  influence  upon  the 
blood-vessels  of  cardiac^  and  striated  muscle  tissue.^  It  stimulates 
the  activitj^  of  the  sahvary  and  lacrimal  glands. 

In  addition  to  these  effects  upon  the  neuromuscular  and  neuro- 
glandular substance,  adrenalin  also  influences  the  metabolism  of  the 
different  food  stuffs,  chiefly  of  the  carbohydrates.  This  deduction  is 
based  upon  the  fact  that  its  administration  gives  rise  to  the  condition 
of  adrenalin-glycosuria,  for  the  obvious  reason  that  it  interferes  in 
some  manner  with  the  oxidation  of  the  sugars.  Its  point  of  attack, 
however,  has  not  been  definitely  ascertained,  although  it  has  been 
stated  by  Underhill  and  Closson'*  that  it  activates  the  sympathetic 
fibers  regulating  the  formation  of  dextrose  from  glj^cogen.  Others, 
again,  beheve  that  it  influences  the  liver  cells  directly,  causing  them 
either  to  discharge  a  more  abundant  amount  of  dextrose  or  to  hinder 
them  in  their  storage  of  glycogen.  At  all  events,  adrenalin  mobiUzes 
dextrose,  but  certainly  not  by  evoking  a  greater  production  of  sugar 
from  proteins  or  fats.  Consequently,  the  condition  of  adrenaUn- 
hyperlgycemia  and  gh-cosuria  cannot  be  directly  related  to  diabetes 

1  Am.  Jour,  of  Physiol.,  ix,  1903,  2.52,  and  ihid.,  xi,  1904,  28. 

2  Gunn,  Quart.  Jour.  Exp.  Phj'siol.,  vii,  1913,  75. 

'  Hoskins,  Gunning  and  Berry,  Am.  Jour,  of  Phj^siol.,  xli,  1916,  513. 
*  Ibid.,  xvii,  1906,  42. 


976 


THE    INTERNAL    SECRETIONS 


mellitus,  because  the  metabolism  of  the  sugars  is  interfered  with  in  this 
disease  in  a  much  more  extensive  manner.^  Since  the  action  of 
adrenahn  seems  to  be  concentrated  upon  tlie  Uver,  it  cannot  surprise 
us  to  find  that  it  also  incites  a  more  copious  discharge  of  other  products. 
Thus,  Cannon-  has  found  that  the  intravenous  injection  of  this  agent 
in  amounts  of  0.0001  mgr.  per  kilo  of  body  weight  (cats)  shortens 
the  coagulation-time  of  the  blood.  In  addition,  it  has  been  shown  by 
Cannon  and  Nice^  as  well  as  by  Gruber*  that  this  procedure  is  followed 
by  a  temporary  improvement  in  the  power  of  contraction  of  fatigued 


Fig.  509. — Median  Sagittal  Section  through  Pituitary  of  Moxket;  Semidiagram- 

MATic.     (Herring.) 
a,  Optic  chiasma;  b,  third  ventricle;  c,  g,  pars  intermedia;  d,  epithelium  of  pars 
intermedia  extending  round  neck  of  pars  nervosa;  e,  pars  glandularis  seu  epithelialis; /, 
intraglandular  cleft,  lying  between  pars  glandularis  (e)   and  pars  intermedia  (;;);  h, 
pars  nervosa. 

muscles,  a  change  which,  owing  to  the  small  doses  employed,  cannot  be 
due  to  improved  cii'culatory  conditions.  More  recently,  it  has  been 
pointed  out  by  Hartmann  and  Fraser^  that  subminimal  doses  of  this 
agent  give  rise  to  a  vasodilatation.  It  should  be  remembered,  how- 
ever, that  these  effects  have  been  obtained  under  experimental  con- 
ditions and  that  they  do  not  justify  the  deduction  that  they  also  occur 
normally  in  consequence  of  the  outpouring  of  varying  amounts  of 
adrenin. 

>  Lusk  and  Riche,  Arch.  Int.  Med.,  xiii,  1914,  673. 

^  Am.  Jour,  of  Physiol.,  x.xxiv,  1914,  255. 

3  Ibid.,  xxxii,  1913,  44. 

*  Ibid.,  xxiii,  1914,  335,  also:  Endocrinologv,  iii,  1919,  145. 

6  Ibid.,  xliv,  1917,  353. 


THE   iMTirrAin    hodv  977 

F.  THE  PITUITARY  BODY  OR  HYPOPHYSIS  CEREBRI 

Position  and  Structure  of  the  Hjrpophysis. — In  Imnuiu  Ijcings  this 
struct  uic  lies  jit  the  base  of  the  brain  directly  behind  the  optic  chiasma; 
and  occupies  a  niche  in  the  seUa  turcica  of  tlie  sphenoid  bone.  It 
appears  as  a  recUhsh-gray  mass  of  about  the  size  of  a  pea  which  is 
connected  with  the  ventricuhir  region  of  the  brain  by  a  narrow  stalk, 
called  the  infundibulum.  The  botly  of  this  gland  consists  of  two  lobes, 
an  anterior  and  a  posterior.  They  are  closely  appi'oxi mated,  the  cleft- 
like space  between  them  b(ung  filhul  with  a  yellowisii  fluid.  Owing  to 
the  fact  that  the  cells  lining  this  spac(^  posteriorly,  present  several 
distinctive  structural  features  and  doubtlessly  secrete  the  aforesaid 
fluid,  they  arc  commonly  regarded  as  forming  a  special  part  of  the 
pituitary  which  is  known  as  the  jxirs  int(>rmedia.  Gross  anatomically, 
liow(>ver,  these  cells  belong  to  the  posterior  lobe. 

The  two  lobes  of  the  hypophysis  differ  widely  from  one  another  in 
their  structure,  development  and  function.  The  posterior  one  is 
developed  as  a  hollow  outgrowth  of  that  part  of  the  embryonic  brain 
which  later  on  becomes  the  third  ventricle.  While  this  communica- 
tion is  obliterated  in  man,  it  remains  open  in  certain  animals.  The 
anterior  lobe  first  appears  as  an  extension  of  the  ectoderm  of  the  buccal 
cavity.  After  the  obliteration  of  this  prolongation,  the  epithelium 
arranges  itself  in  the  form  of  trabeculse  which  are  invested  by  a  close 
network  of  uncommonly  large  capillaries,  and  contain  certain  cells 
which  are  sharply  differentiated  from  the  others  by  their  content  in 
deeply  staining  granules  of  chromophil.  Contrary  to  the  general 
neuroglia-like  character  of  the  posterior  lobe,  the  pars  intermedia  has 
the  appearance  of  ependymal  tissue.  Herring^  has  called  attention 
to  the  fact  that  these  cells  embrace  a  material  which  stains  in  the  form 
of  globular  masses  of  colloid-Uke  material.  From  this  brief  structural 
survey  it  may  be  gathered  that  the  anterior  lobe  possesses  the  character- 
istics of  a  ductless  gland  which  discharges  its  product  directly  into  the 
blood-stream, 2  while  the  intermediate  part  discharges  its  secretion  into 
the  infundibular  space  and  the  cerebral  ventricles.  The  structure  of 
the  posterior  part,  on  the  other  hand,  would  not  lead  us  to  infer  that 
it  possesses  a  secretory  function. 

Removal  of  the  Hypophysis. — The  experiments  of  Horsley  (1885), 
Dastre  (1889),  and  Clay  (1891)  have  shown  that  the  total  removal  of 
the  hypophysis  is  followed  by  death  within  a  few  days,  the  symptoms 
displayed  by  these  animals  being  similar  to  those  following  the  extir- 
pation of  the  thyroid  or  adrenal  bodies.  But  since  this  organ  is  very 
inaccessible,  some  of  these  symptoms  may  not  be  caused  by  the  loss 
of  the  hypophysis  at  all,  but  by  injuries  to  neighboring  parts,  such  as 
the  tuber  cinereum  with  which  its  anterior  portion  lies  in  close  contact. 
This  possibility,  however,  does  not  seem  to  have  played  an  actual 

1  Quart.  Jour,  of  Exp.  Physiol.,  i,  1908,  121. 

2  Bell,  ibid.,  xi,  1917,  77. 


978  THE    INTERNAL    SECRETIONS 

part,  because  the  subsequent  experiments  of  Caselli  (1900),  Gaglio 
(1902),  Fischcra  (1905),  Aschner  (1912),  Biedl  (1913),  and  Gushing,' 
have  given  practically  identical  results.  Only  a  few  of  the  hypophy- 
sized  animals  survived  for  a  longer  period  than  two  or  three  months, 
and  in  these  it  was  impossible  to  determine  whether  any  of  the  essential 
tissue  had  been  left  behind.  It  was  also  demonstrated  in  these  animals 
that  the  two  lobes  of  this  organ  possess  different  functions,  the  extirpa- 
tion of  the  anterior  one  proving  fatal  immediately,  while  that  of  the 
posterior  one  did  not  produce  decisive  symptoms  for  some  time  there- 
after. In  the  latter  case,  the  animals  usualh'  died  from  some  incurrent 
condition.  Likewise,  no  immediate  sj^mptoms  developed  after  the 
partial  removal  of  the  anterior  lobe,  the  animals  meanwhile  acquiring 
extensive  layers  of  fat  in  the  omentum  and  retroperitoneal  spaces, 
and  gradually  developing  a  condition  very  similar  to  infantihsm. 

Pituitrin. — ^Subsequent  to  the  observation  of  Oliver  and  Shafer,^ 
that  the  extract  of  the  h^-pophysis  gives  rise  to  a  marked  increase  in 
blood  pressure,  a  substance  was  isolated  from  the  posterior  lobe  to 
which  the  name  of  pituitrin  or  hj^jophA'sin  has  been  given. ^  When 
injected  into  the  venous  blood-stream,  this  agent  raises  the  arterial 
pressure  very  materially  as  weU  as  for  a  considerable  period  of  time. 
There  is  no  doubt  that  this  liA-j^ertension  originates  chiefly  in  a  con- 
striction of  the  peripheral  blood-vessels,  although  this  substance  also 
seems  to  strengthen  and  to  slow  the  heart  beats.  When  compared 
with  the  action  of  adrenahn,  it  must  be  conceded  that  it  produces  a 
much  more  lasting  although  not  quite  so  powerful  effect,  and  that  its 
action  is  exerted  upon  the  muscle  tissue  directly  and  not  upon  the 
nervous  terminals.'* 

The  Function  of  the  Posterior  Lobe  of  the  Hypophysis. — When 
studj'ing  the  action  of  extracts  of  the  entire  posterior  lobe,  it  must 
be  remembered  that  the  active  principle  here  involved  is  a  product  of 
its  glandular  pars  intermedia  and  not  of  its  neuroglia-like  posterior 
portion.  When  injected  intravenously,  such  extracts  cause  the  smooth 
muscle  tissue  throughout  the  body  to  contract,  thereby  constricting 
the  arteries  and  arterioles  and  raising  the  arterial  pressure.  The 
same  effect  is  produced  upon  the  urinary  bladder  and  uterus,  both  these 
organs  being  contracted  veiy  powerfully  but  more  so  by  the  first 
injection  than  by  the  subsequent  injections.^  Upon  this  action  is 
based  the  therapeutic  value  of  pituitrin  as  an  agent  promoting  the 
emptying  of  the  pregnant  uterus,  but  its  application  in  obstectrical 
practice  should  be  restricted  to  particular  cases.  It  is  a-  safe  agent  in 
the  hands  of  only  the  most  experienced  practitioners. 

1  The  Pituitary  Body  and  Its  Disorders,  1912,  also  see:  Houssay,  La  accion  fis. 
de  los  extr.  hipofisiarios,  Flaiban,  Buenos  Aires,  1918. 
-  Jour,  of  Phj-siol.,  .xviii,  1S9.5,  23. 

3  Engeland  and  Kutscher,  Zeitschr.  fiir  Biol.,  Ivii,  1911,  527. 
^  Cramer,  Quart.  Jour.  Exp.  Physiol.,  i,  190S.  189. 
.    *  Frankl-Hochwarth   and  FrohUch,  Wiener  klin.  Wochenschr.,  1909. 


THE    PITUITARY   BODY  979 

In  addition,  pituitrin  stimulates  the  flow  of  certain  socrotions. 
Thus,  it  has  been  observed  by  Ott  and  Scott'  that  it  causes  a  copious 
flow  of  milk  from  the  mammary  ji;lands,  if  administered  to  pregnant  or 
parturient  cats  and  other  animals.  In  woman,  it  gives  rise;  to  a  simi- 
lar eflect  which  is  initiated  by  a  feeling  of  pressure  and  discomfort  in 
the  mammiE.  At  the  present  time,  however,  it  cannot  be  stated  defi- 
nitely that  it  serves  as  an  actual  stimulant  to  the  secreting  cells,  be- 
cause its  action  may  l)e  an  indirect  one,  effected  by  contracting  the 
smooth  muscle  cells  lining  the  lactiferous  ducts.  In  addition  to  its 
action  as  a  galactagogue,  it  exerts  a  favorable  influence  upon  the  for- 
mation of  the  cerebrospinal  fluid  and  urine.  In  the  latter  case,  it  is  still 
doubtful  whether  its  diuretic  influence  is  due  to  its  power  of  augment- 
ing the  circulation  or  to  a  stimulating  influence  upon  the  renal  cells. 

The  Function  of  the  Anterior  Lobe  of  the  Hjrpophysis. — In  con- 
tradistinction to  the  posterior  lobe,  extracts  of  the  anterior  lobe  pro- 
duce no  immediate  changes  when  injected  into  the  blood-stream. 
Contrariwise,  the  studies  of  Pierre  Marie^  upon  the  disease,  known  as 
acromegaly,  have  proved  beyond  doubt  that  the  pathogenesis  of  this 
form  of  gigantism  is  in  some  w^ay  connected  with  the  hypophysis. 
Clinically,  acromegaly  presents  itself  as  a  complex  of  symptoms 
suggesting  the  presence  of  a  cerebral  tumor.  The  patient,  usually 
an  adult,  complains  of  headache,  vertigo,  vomiting,  failing  in  intelli- 
gence, somnolence,  hemianopsia,  and  progressive  amblyopia.  The 
face  becomes  distorted,  owing  to  an  enlargement  of  the  facial  bones  and 
soft  parts;  the  lips  swell;  the  eyelids  thicken,  and  the  lower  jaw  be- 
comes very  prominent.  The  other  forms  of  gigantism  appear  early  in 
life  and  are  characterized  by  an  excessive  growth  of  certain  bones, 
chiefly  the  long  bones  and  those  of  the  face.  In  all  these  cases,  it  has 
been  ascertained  that  the  hypophysis  is  very  active,  as  is  evinced  by 
its  large  size  and  a  hvperplasia  of  the  glandular  elements  of  the  an- 
terior lobe.^  It  has  also  been  demonstrated  that  this  gland  is  rudi- 
mentary in  true  dwarfs. 

In  correlating  these  clinical  pictures  of  hyper  and  hypopituitarism, 
it  is  made  obvious  by  exclusion  that  the  anterior  lobe  of  the  hypophysis 
produces  a  hormone  which  controls  the  growth  of  the  connective  tis- 
sues. In  the  absence  of  this  internal  secretion  in  young  animals, 
their  growth  is  checked  so  that  they  gradually  pass  over  into  a  condi- 
tion of  infantilism.  Conversely,  a  hyper-activity  on  the  part  of  this 
gland  gives  rise  to  gigantism,  general  and  local.  This  result  may  be 
produced  either  directly  through  the  action  of  this  hormone  upon  the 
nervous  system,  or  indirectly  through  its  action  upon  other  internal 
glands  of  the  metabolic  type,  such  as  the  thyroid  and  thymus.     This 

^  Therap.  Gazette,  xxxv,  1911,  and  Simpson  and  Hill,  Am.  Jour,  of  Physiol., 
.\xxvi,  1915.  77. 

2  Brain,  xii,  1890,  59,  and  Marie  and  Marinesco,  Arch,  de  m^d.  exp.  et  d'anat. 
path.,  1891. 

'  Benda,  Handb.  der  path.  Anat.  des  Xervensystemes,  Berlin,  1904. 


980  THE  INTERNAL  SECRETIONS 

conclusion  is  strengthened  materially  by  the  results  of  organotherapy. 
Thus,  Robertson^  has  succeeded  in  isolating  a  substance  which  he 
calls  tethehn.  It  contains  nitrogen  and  phosphorus  and  exerts  a 
stimulating  influence  upon  the  growth  of  mice.  Favorable  results 
have  also  been  obtained  by  Schafer^  by  feeding  preparations  of  the 
anterior  lobe  to  young  rats.     Magnus,  Levy  and  Falta  report  that  the 


Fig.  510. — Acromegaly. 
This  man  was  an  acromegalic  giant  aged  thirty-five,  with  blindness  and  large  tumor 
of  the  hypophysis.      (Cushing.) 

administration  of  extracts  of  the  hypophysis  increases  the  decomposi- 
tion of  the  proteins. 

G.   THE  PINEAL  GLAND  OR  EPIPHYSIS  CEREBRI 

Position  and  Function  of  the  Pineal  Gland. — In  man  this  structure 
lies  free  between  the  anterior  corpora  quadrigemina,  its  base  being 
directed  forward  across  the  roof  of  the  third  ventricle.  In  early  life 
it  exhibits  a  glandular  appearance  and  is  subdivided  by  connective 
tissue  septa  into  lobules  which  are  made  up  of  pale  granular  cells. 
At  about  the  seventh  year  it  shows  signs  of  involution,  its  glandular 

1  Jour,  of  Biol.  Chem.,  xxiv,  1916,  397,  and  Schmidt,  Jour.  Lab.  Clin.  Med., 
ii,  1917,  719. 

2  Quart.  Jour,  of  Exp.  Physiol.,  v,  1912,  203. 


THE    CKMTAL    OUOANS  981 

elements  then  being  griulually  displaced  by  connective  tissue  and 
glia  tissue  of  a  very  fibrous  type.  Hyaline  degeneration  sets  in,  lead- 
ing to  the  formation  of  calcareous  concretions  of  calciuni  phosphate 
and  calcium  carbonate  which  constitute  the  so-called  brain-sand. 

Virchow  first  called  attention  to  the  fact  that  the  pineal  gland  is 
frequently  the  seat  of  cystic  growths  and  gliomas.  The  clinical  picture 
presented  bj'^  persons  so  afflicted  is  very  similar  to  that  noted  in  diseases 
of  the  pituitary  body,  Avith  the  exception  that  sexual  infantilism  is 
absent.^  There  may  be  observed  an  obesity  and  cachexia  as  well  as 
certain  trophic  disturbances.  Further  than  this  no  definite  statements 
can  be  made,  as  is  evinced,  for  example,  by  the  recent  papers  of  Horrp.x^ 
and  McCord.^  The  first  of  these  leads  us  to  infer  that  the  removal 
of  this  gland  in  male  guinea-pigs  favors  the  development  of  the  sexual 
organs  and  hastens  the  sexual  maturity  and  breeding  power  of  the 
female.  The  second  paper,  on  the  other  hand,  informs  us  that  the  feed- 
ing of  pineal  gland  to  young  guinea-pigs  hastens  their  sexual  maturity 
and  favors  their  growth.  These  series  of  experiments,  therefore,  would 
lead  to  believe  that  hypo  and  hyperpinealism  produce  practically 
homologous  results,  and  that  the  extract  of  this  organ  acts  as  a  chalone 
as  well  as  a  hormone.  Obviously,  further  investigation  is  urgently 
needed  to  clear  up  this  point. 

H.    THE  GENITAL    ORGANS 

The  Function  of  the  Ovaries. — Since  the  external  and  internal 
secretions  of  these  organs  will  be  dealt  with  in  greater  detail  in  a 
later  chapter,  the  present  discussion  may  well  be  restricted  to  the 
chemical  interrelationship  existing  between  these  structures  and 
others.  In  the  fiirst  place,  it  should  be  noted  that  the  secretion  of  the 
ovaries  may  produce  either  a  local  or  a  general  effect.  Thus,  it  is  a 
well-known  fact  that  castration  in  women  is  followed  by  regressive 
changes  in  their  genitals,  such  as  atrophy  of  the  uterus  and  vagina. 
This  fact  has  led  to  the  assumption  that  the  ovaries  serve  as  the  trophic 
center  for  these  parts,  but  since  the  transplantation  of  these  organs  or 
the  grafting  of  a  part  of  their  tissue  in  other  regions  of  the  body  does 
not  allow  this  condition  to  be  developed,  this  control  must  be  exercised 
by  them  with  the  aid  of  some  chemical  agent.  This  deduction  is  also 
justified  by  a  study  of  the  relationship  existing  between  ovulation  and 
menstruation,  because  it  is  entirely  probable  that  the  latter  process  is 
initiated  by  an  active  principle  secreted  by  the  cells  forming  the  corpus 
luteum.  Lastly,  this  conclusion  is  upheld  by  the  disturbing  general 
symptoms  which  generally  follow  in  the  wake  of  castration.  It  is  a 
matter  of  common  experience  that  a  woman  whose  ovaries  have  been 
removed  for  the  cure  of  a  tumor  or  cystic  growth,  very  frequently 

^  Deutsche  Zeitschr.  fiir  Nervenheilkunde,  1909. 

2  Arch.  Int.  Med.,  1916. 

3  Proc,  Am.  Med.  Assoc,  June,  1914. 


982  THE  INTERNAL  SECRETIONS 

develops  well-defined  general  symptoms  of  a  nervous  and  metabolic 
kind.  These  disturbances  are  manifested  most  typically  by  vaso- 
motor reactions,  commonly  called  "hot  flushes, "  sensations  of  alternat- 
ing heat  and  cold,  sweating,  vertigo,  muscular  pains,  and  headache. 
In  fact,  in  severe  cases  certain  psychoneurotic  conditions  may  arise 
which  finally  lead  to  mental  aberrations.  The  contention  that  these 
symptoms  are  attributable  to  the  loss  of  an  internal  secretion  of  the 
ovaries,  is  strikingly  betrayed  by  the  results  of  organotherapy.  If  an 
extract  of  whole  ovary  is  administered  to  the  castrated  women,  these 
symptoms  most  generally  lose  their  intense  character  and  are  shortened 
in  their  duration;  in  fact,  it  is  not  at  all  uncommon  to  see  them  disap- 
pear altogether  in  consequence  of  this  treatment.  Moreover,  the  fact 
that  extracts  of  the  entire  ovary  are  more  beneficial  than  extracts  of 
corpus  luteum,  seems  to  show  that  this  general  metabolic  hormone  is 
not  necessarily  a  product  of  the  corpus  luteum  or  Graafian  follicles. 
Bouin^  refers  this  function  to  the  peculiar  stroma  cells  which  he 
designates  as  the  glande  inter stitielle  Vovaire. 

While  these  local  and  general  effects  following  the  removal  of  the 
ovaries,  are  quite  definite,  it  has  not  been  established  as  yet  whether 
the  active  principle  of  these  organs  acts  directly  or  indirectly  through 
the  secretions  of  other  ductless  glands.  It  has  previously  been  shown 
that  the  ovary  is  in  functional  relation  with  other  endocrine  organs, 
thus  forming  a  special  group  which  might  be  named  the  sexual  glands. 
It  is  a  well-known  fact  that  Graves  disease  is  very  deleterious  to  preg- 
nancy and  that  operations  upon  the  pelvic  organs  are  prone  to  intensify 
the  symptoms  of  hyperthyroidism.  Castration  also  increases  the 
weight  of  the  hypophysis,  thymus,  and  adrenal  glands. 

The  Function  of  the  Testes. — It  has  been  known  for  some  time  that 
the  testicles  furnish  an  internal  secretion  in  addition  to  their  external 
product,  the  spermatozoa.  Quite  aside  from  the  claim  of  Brown- 
Sequard,  that  extract  of  testicle  possesses  an  invigorating  influence,  it 
has  been  shown  by  PoehP  that  "spermin"  acts  as  a  "physiological 
catalytic"  and  increases  the  action  of  the  heart  and  digestive  organs. 
Later  on  Zoth  and  PregP  proved  by  means  of  the  ergograph  that 
testicular  extract  augments  the  muscular  power  by  as  much  as  50 
per  cent,  and  diminishes  muscular  fatigue.  A  more  general  influence 
of  the  testes  upon  the  general  condition  of  the  body  is  evinced  by  the 
symptoms  following  the  total  removal  of  these  organs.  This  proce- 
dure which  is  commonly  known  as  castration  or  spaying,  has  been 
practised  upon  animals  since  the  earHest  times.  In  the  case  of  the 
domestic  animals,  such  as  the  bulls,  stallions,  rams  and  cocks,  the  in- 
variable result  is  an  insufficient  development  of  the  sexual  organs  and 
secondary  sexual  characteristics.  Their  transformation,  however,  is 
never  complete,  i.e.,  castrated  males  never  completely  assume  the 

1  Compt.  rend.,  1907,  337. 

2  Zeitschr.  ftir  klin.  Med.,  1894. 

3  Pfliiger's  Archiv,  Ixii,  1896,  335. 


THE    GENITAL    ORGANS  983 

characteristics  of  the  opposite  sex.  Thus,  while  th(!  ram  himbs  may 
develop  horns,  the  further  growth  of  the  latter  is  arrested  at  an  early- 
stage.  Quite  similarly,  the  castrated  cock  shows  an  eai-ly  withering  of 
the  comb  and  wattles.  The  loss  of  these  and  other  secondary  char- 
acteristics, however,  may  be  prevented  by  removing  only  one  testicle 
or  by  grafting  one  in  some  other  part  of  the  body. 

Very  similai'  effects  have  been  noted  in  human  beings.  Thus,  it 
is  a  well-known  clinical  fact  that  castration  inhibits  the  growth  of  the 
prostate  and  actually  incites  retrogressive  changes  in  this  organ.  In 
castrated  dogs,  this  atrophy  may  be  greatly  retarded  by  the  subcu- 
taneous injection  of  testicular  extract.  Th(!  stories  of  the  East  also 
tell  us  that  castration,  when  effected  during  the  prepubescent  period, 
gives  rise  to  a  defective  development  of  the  sexual  organs  which, 
however,  involves  the  penis  in  a  lesser  degree  than  the  purely  glandular 
tissues,  such  as  the  seminal  vesicles  and  the  prostate.  This  difference 
is  easily  explicabk^  upon  the  ground  that  the  penis  is  chiefly  composed 
of  connective  tissue.  In  these  individuals,  the  secondary  sexual 
characteristics  are  seldom  fully  developed,  as  is  shown  by  the  fact  that 
the  pelvis  of  eunuchs  generally  retains  its  infantile  character,  and  that 
the  amount  of  axillary  and  pubic  hair  is  usually  very  slight.  The 
child-Uke  soprano  character  of  their  voice  is  referable  to  an  arrested 
growth  of  the  larynx.  Moreover,  they  are  prone  to  become  phlegmatic 
and  to  develop  a  heavy  panniculus  acliposus  which  smoothens  their 
contours  and  gives  them  a  feminine  appearance.  These  observations 
may  in  a  large  measure  be  repeated  by  a  study  of  hermaphroditism  in 
animals  and  man,  but  sexual  dimorphism  does  not  always  remain 
confined  to  the  primary  sexual  characteristics  but  may  also  involve 
secondarj^  ones.  The  "feminine"  man  and  "masculine"  woman 
are  instances  of  this  type  of  hermaphroditism,  showing  unisexual 
mechanisms  but  heterologous  secondary  characteristics. 

It  cannot  be  doubted,  therefore,  that  the  testes  control  the  develop- 
ment of  the  sexual  characteristics.  This  end  they  are  able  to  attain 
by  means  of  a  chemical  agent  and  not  by  nervous  reflexes.  In  seeking 
the  place  of  origin  of  this  hormone,  it  is  of  interest  to  note  that  the 
ligation  of  the  vas  deferens,  brings  about  a  retrogression  of  the  sper- 
matogenetic  elements  but  not  of  the  interstitial  cells  of  these  organs. 
Contrary  to  the  castrated  animals,  these  animals  show  perfectly  nor- 
mal sexual  characteristics  and  instincts.^  Furthermore,  Steinach^ 
has  proved  that  the  transplantation  of  the  testes  does  not  destroy 
these  tendencies  and  that  the  transplanted  organ  exhibits  a  proUfera- 
tion  of  its  interstitial  cells  and  an  atrophy  of  its  spermatozoid  cells. 
In  this  connection,  it  is  also  of  interest  to  note  that  transplantations 
in  very  young  animals  may  give  rise  to  an  almost  complete  reversion 
of  the  secondary  sexual  characteristics.  Thus,  the  grafting  of  an  ovary 
from  a  female  rat  or  guinea-pig  into  a  young  castrated  male  of  the 

1  Tandler,  Wiener,  klin.  Wochenschr.,  1908,  1910. 
^  Steinach,  Pflliger's  Archiv,  cxliv,  1912,  71. 


984  THE  INTERNAL  SECRETIONS 

same  species  produced  a  pseudo-hermaphrodite,  which  presented  primi- 
tive male  generative  organs  and  female  secondary  characteristics. 
In  conclusion,  it  may  therefore  be  stated  that  the  internal  secretion 
of  the  male  generative  gland  is  furnished  by  the  interstitial  cells  of 
Leydig.  Enclosed  in  the  cytoplasm  of  these  cells  we  find  granules 
and  peculiar  crystals  which  impart  to  them  the  appearance  of  true 
secretory  elements.  These  bodies  may  be  the  precursors  of  this 
internal  product. 


PART  VIII 
METABOLISM 

SECTION  XXVI 
DIGESTION 

CHAPTER  LXXXIII 

THE  CHEMISTRY  OF  DIGESTION 

General  Consideration. — The  term  of  assimilation  as  originally 
employed  by  the  botanists,  included  all  those  processes  which  the 
plants  must  undergo  in  order  to  synthetize  the  inorganic  substances 
into  the  organic  compound  starch.  When  employed  in  this  general 
way,  it  embraces  all  those  chemical  and  mechanical  processes  which 
lead  to  the  reduction,  absorption  and  assimilation  of  the  different 
foodstuffs  by  the  cells.  These  stages  are  followed  by  cellular  dissimi- 
lation and  excretion.  At  the  present  time,  all  these  processes  are 
generally  included  under  the  term  of  metabohsm  which  is  divided  in 
turn  into  a  process  of  building  up,  or  anabohsm,  and  a  process  of  tear- 
ing down,  or  catabolism,  as  follows: 

C  Ingestion 

.      ,    ,.  J  Digestion 

Anabolism    <    ., 

I  Absorption 

,,,,,•         1  I  Assimilation 

Metabolism  i 

r^  i.  u  1-         r  Dissimilation 
Catabolism   <  -r-, 

I  Excretion 

In  the  lower  forms,  the  process  of  digestion  is  completed  outside 
the  cells,  enabling  them  to  attain  their  nutritive  material  in  a  fluid 
condition  ready  for  assimilation.  Beginning  with  the  celenterates, 
on  the  other  hand,  digestion  is  chiefly  intracellular  and  hence,  the 
metabolism  of  the  higher  forms  requires  the  presence  of  special  organs, 
the  purpose  of  which  is  to  reduce  the  nutritive  material  sufficiently 
to  render  it  dialyzable  through  animal  membranes,  and  assimilable 
by  the  cells.  But  since  the  food  must  be  reduced  mechanically  as  well 
as  chemically,  two  types  of  organs  must  really  be  present  which  sever- 
ally accomplish  these  ends.     In  most  instances,  however,  the  mechan- 

985 


986  DIGESTION 

ical  and  chemical  mechanisms  are  combined  in  such  a  way  that  both 
kinds  of  reductions  may  be  had  within  the  confines  of  the  same  organ. 
Obviously,  the  histological  elements  more  directly  concerned  with  them, 
are  the   striated  and  smooth  muscle  cells  and  the  gland  cells. 

The  food  made  use  of  by  the  higher  animals,  is  heterogeneous  m 
its  character,  consisting  of  inorganic  and  organic  principles,  and  a 
certain  amount  of  non-digestible  and  non-nutritive  material,  such  as 
connective  tissue  and  the  cellulose  of  the  plants.  The  predigcstive 
procedures  which  man  employs  in  preparing  his  food,  cannot  materially 
alter  this  condition,  because  only  very  few  non-assimilable  mate- 
rials can  be  made  available  thereby.  This  is  true  of  the  process 
of  cooking  as  well  as  of  that  of  maceration.  All  that  can  be  accom- 
plished by  these  means  is  to  free  the  nutritive  principles  from  their 
non-digestible  investments,  and  to  increase  the  solvent  action  of  the  dif- 
ferent digestive  juices,  so  that  they  may  be  more  readily  reduced,  chemi- 
cally as  well  as  mechanically.  Nutritive  material  is  consumed  in  the 
form  of  food,  consisting  of  different  foodstuffs.  Consequently,  a 
food  is  a  mixture  of  nutritive  substances,  whereas  a  foodstuff  is  a 
single  nutritive  substance.  The  latter  are  grouped  as  water,  salts, 
carbohydrate,  fat,  and  protein,  and  may  be  arranged  as  nitrogenous 
and  non-nitrogenous  substances,  as  follows: 

Organic  Inorganic 


Nitrogenous  Non-nitrogenous  (Non-nitrogenous) 


Proteins  Fats  Carbohydrates  Salts        Water 

Obviously,  the  purpose  of  food  is  to  replenish  the  material  which 
nas  been  used  up  by  the  cells  during  their  oxidations  in  furnishing  the 
energy  upon  which  the  bodily  machine  is  run.  Were  this  waste  to  con- 
tinue without  being  balanced  by  an  adequate  intake,  the  animal 
would  soon  have  to  discontinue  its  activities.  Moreover,  since  food 
as  exemphfied  by  meat,  potatoes,  milk,  bread,  etc.,  is  invariably 
made  up  of  several  foodstuffs,  it  will  be  seen  that  our  diet  usually 
consists  of  several  of  the  proximate  principles  just  mentioned.  In 
fact,  no  diet  can  be  regarded  as  adequate  for  man  which  does  not  em- 
brace all  the  different  foodstuffs,  mixed  in  proper  proportion,  to  burden 
the  body  with  only  a  minimum  of  labor. 

Water,  salts  and  some  carbohydrates,  such  as  dextrose,  are  capable 
of  traversing  the  intestinal  epithehum  in  their  original  form,  whereas 
the  indiffusible  colloidal  carbohydrates,  such  as  starch  and  dextrin, 
must  first  be  converted  into  soluble  and  diffusible  sugar.  This  is 
also  true  of  the  fats  which  must  first  be  changed  into  glycerin  and  fatty 
acids,  and  the  natural  proteins  which  must  first  be  converted  into  dif- 
fusible peptones  and  simpler  compounds.  As  stated  above,  digestion 
does  not  end  here^  but  in  addition  imparts  to  the  now  diffusible  end- 
products  of  the  different  foodstuffs  a  form  which  will  enable  the  cells 


THE    CHEMISTRY    OV    DIGESTION  987 

of  the  tissues  to  utilize  them.  For  this  reason,  the  disaccharifles,  such 
as  cane-sugar,  nuihose,  antl  lactose,  are  first  converted  into  mono- 
saccharides, such  as  dextrose,  levulose,  and  galactose,  while  the  pro- 
tein mol(>cule  is  split  up  into  amino-acids. 

Ferments. — The  word  ferment  was  formerly  applied  to  living 
organisms  such  as  the  yeast  cells,  which  during  their  conversion 
of  sugar  into  carbonic  acid  and  alcohol,  cause  the  liquid  to  boil  up 
(fervere),  owing  to  the  evolution  of  this  gas.  For  similar  reasons  this 
entire  process  was  designated  as  fermentation.  In  recent  years, 
however,  many  similar  sul)stances  have  been  found  in  animal  and  vege- 
table cells,  so  that  the  term  of  ferment  is  now  applied  to  all  those  com- 
plex organic  bodies  which  are  capable  of  inciting  a  chemical  reaction 
without  they  themselves  undergoing  a  quantitative  or  qualitative  alter- 
ation. Hence,  any  fermentation  must  derive  the  energy  evolved  in 
the  course  of  this  process  from  the  substances  concerned  in  it  and  not 
from  the  activating  agent.  Besides,  no  direct  relationship  can  exist 
between  the  amount  of  the  ferment  and  the  intensity  of  the  reaction. 
This  imphes  that  even  the  most  minute  amounts  of  ferment  are  capable 
of  inducting  chemical  changes  in  proportionately  much  larger  quan- 
tities of  reducible  material,  and  that  the  addition  of  more  ferment  can 
only  serve  to  quicken  the  reaction,  and  not  to  alter  its  character.  A 
chemical  change  of  this  kind  is  known  as  a  catalysis,  while  the  agent 
producing  it  is  designated  as  a  catalyzer  or  catalyst.  The  sub- 
stance acted  upon  bj-  the  catalyzer  is  termed  the  substrate.  There 
are,  of  course,  manj^  other  catalytic  agents  besides  the  ferments. 
Thus,  potassium  chromate  may  act  as  the  catalyzer  for  the  oxidation 
of  hydriodic  acid  by  bromic  acid  or  spongy  platinum,  and  may  cause 
the  spontaneous  combustion  of  hydrogen  peroxide  into  water  and 
oxygen. 

Until  comparatively  recently,  ferments  have  been  classified  as 
organized  and  unorganized,  or  as  Uving  and  dead.  Among  the  former 
might  be  mentioned  the  yeast  plant  or  saccharomycetes,  and  a  large 
number  of  bacteria,  and  among  the  latter,  the  different  active  princi- 
ples of  the  digestive  juices,  such  as  ptyalin,  pepsin,  trypsin,  and  others. 
On  the  one  hand,  therefore,  w'e  have  living  cells  possessing  a  distinct 
organization,  and,  on  the  other,  dead  sustances,  which  in  most 
instances  have  not  been  satisfactorily  isolated  and  are  known  to  be 
present  solely  from  the  reactions  incited  by  them.  While  this  classifica- 
tion is  easily  understood,  it  is  no  longer  tenable,  because  it  has  been 
shown  that  the  yeast  cell  and  alhed  living  entities  may  be  made  to 
give  up  their  ferments  by  chemical  means  without  that  the  latter 
lose  their  power  of  inciting  fermentation.  In  other  words,  it  is  not  at 
aD  essential  to  the  action  of  the  ferment  that  it  be  carried  by  Hving 
matter,  and  hence,  it  must  be  considered  merely  as  a  product  of  cellular 
metabolism.  Consequently,  it  is  really  as  "unorganized"  as  the 
enzyme  of  the  cells  of  the  salivary  glands  or  any  other  (Buchner 
1897),  and  hence,  the  terms  of  ferment  and  enzyme  are  now  synonymous 


988  DIGESTION 

in  their  meaning.  The  distinction  commonly  made  between  them 
at  the  present  time,  is  based  upon  their  place  of  action.  Thus,  we  may 
speak  of  an  intracellular  or  endo-enzyme,  when  it  acts  in  the  cells  in 
which  it  originated,  and  of  an  extracellular  or  exo-enzyme,  when  it 
acts  outside  its  mother-cell.  There  is  every  reason  to  believe  that 
the  action  of  yeast  is  due  to  the  intracellular  behavior  of  its  endo- 
enzyme  (zymase),  while,  for  example,  saliva  owes  its  chemical  power 
to  its  extracellular  exo-enzyme,  ptyalin.^ 

The  Nature  of  Ferments. — Since  ferments  are  not  destroyed  in 
the  course  of  the  processes  incited  by  them,  the  medium  must  contain 
them  even  after  the  reaction  has  ceased.  In  the  cells  themselves 
they  are  held  in  an  inactive  form  which  is  somewhat  different  from  that 
of  the  active  derivative.  But,  the  fact  that  ferments  are  never  pres- 
ent in  abundant  amounts  is  not  the  only  difficulty  met  with  in  isolat- 
ing them  in  a  sufficiently  pure  state  to  determine  their  chemical  nature. 
Many  of  them  are  very  unstable  and  are  rendered  inert  at  80°C., 
and  all  of  them  are  colloidal  or  semi-colloidal  in  their  nature  and  not 
easily  diffusible.  Wliile  this  peculiarity  enables  them  to  adhere  to 
other  colloidal  material  as  well  as  to  precipitates,  it  does  not  materially 
facilitate  their  isolation,  because  the  attempt  of  separating  them  most 
generally  diminishes  their  power  of  producing  their  characteristic 
reaction,  and  hence,  destroys  practically  the  only  means  of  detecting 
their  presence  and  identity. 

Since  ferments  are  formed  from  Uving  matter,  they  have  been 
considered  as  belonging  to  the  class  of  the  proteins.  But,  inasmuch 
as  their  separation  from  these  substances  cannot  be  effected  with 
certainty,  the  fact  that  many  of  them  give  the  characteristic  reactions 
of  proteins  cannot  serve  as  a  means  of  identifying  them,  because  these 
positive  results  may  be  due  to  the  protein  material  which  is  still 
adherent  to  them.  Consequently,  it  must  suffice  at  this  time  to  desig- 
nate them  as^  organic  substances  which  are  derived  from  proteins 
and  possess  a  colloidal  nature. 

Classification  of  Ferments. — Ferments  are  almost  universally 
present  in  nature.  So  great  is  their  number,  that  the  present  discus- 
sion must  be  restricted  to  those  which  take  a  more  direct  part  in  the 
economy  of  the  animal  body.  Moreover,  since  we  know  more  about 
digestion  than  we  do  about  the  processes  of  cellular  assimilation,  any 
enumeration  of  this  kind  must  be  characterized  by  a  preponderance 
of  the  digestive  enzymes.  This  fact  is  largely  responsible  for  the  cus- 
tom of  arranging  them  in  accordance  with  the  character  of  the  reaction 
produced  by  them,  as  follows; 

^  Since  these  topics  are  exhaustively  dealt  with  in  Mathews'  and  Hammarsten's 
Textbooks  of  Physiological  Chemistry,  I  shall  discuss  these  purely  chemical  data  as 
briefly  as  possible.  More  complete  references  will  also  be  found  in  Oppenheimer's 
Handb.  der  Biochemie,  1910,  and  "Die  Fermente  and  ihre  Wirkungen,"  1903; 
Vernon's  "Intracellular  Enzymes,"  1908;  Euler's  "General  Chem.  of  the  Enzymes" 
(trans^.  by  Pope)  1912,  and  Bayliss,  "The  Nature  of  Enzyme  Action,"  1908. 


THE    CHEMISTIIV    OF    DIGESTION 


989 


(a)  Proteolytic  or  protein-splitting  (Mizynios,  such  as  pepsin,  give  rise  to  a 
hydrolytic  cleavage  of  the  protein  molecule. 

(b)  Lipolytic  or  fat-splitting  enzymes,  such  as  stcapsiti,  cause  a  hydrolytic 
cleavage  of  the  fat  molecule. 

(c)  Amylolytic  or  starch-splitting  enzymes,  such  as  ptyaliu,  produce  a  hydro- 
lytic cleavage  of  the  starch  molecule. 

{(I)  Inverting  enzymes,  such  as  maltase,  s|)lit  the  disaccharides  iiitt)  monosac- 
charides and  the  latter  into  simpler  moleeuhs. 

(e)  O.xidizing  enzymes,  such  as  the  oxidases  of  the  tissues,  which  aid  in  internal 
respiration. 

(J)  Coagulating  enzymes,  such  as  rennin,  wliich  change  soluble  into  insoluble 
proteins. 

(g)  Diaminizing  enzymes,  such  as  alanin,  whicli  split  ofT  an  NHo  group  from  an 
amino-acid  as  ammonia. 

In  the  following  table  are  included  some  of  the  ferments  with  which 
we  are  chiefly  concerned  at  the  present  time,  it  being  the  custom 
to  designate  them  by  the  name  of  the  substance  upon  which  they  act 
and  to  affix  the  letters,  ase.  This  suggestion  (Duclaux)  has  been  fol- 
lowed in  most  instances,  the  only  exceptions  being  those  enzymes  which 
have  been  recognized  for  a  long  time,  such  as  ptyalin,  pepsin  and  trypsin. 


Ferment 

Place  of  action 

Character  of  action 

Ptyalin 

Saliva 

Starch — maltose 

Amylopsin 

Pancreatic  juice 

Starch — maltose 

Glycogenase 

Liver  and  muscles 

Gl.vcogen — dextrose 

Amylolytic 

Invertase 

Small  intestine 

Cane-sugar — dextrose 

and 

Maltase 

Saliva  and  small  intestine 

Maltose — dextrose 

inverting 

Lactase 
Lactic  acid 

Small  intestine 

Lactose — dextrose  and  galactose 

ferment 

Intestine 

Glucose — lactic  acid 

Steapsin 

Pancreatic  juice 

Neutral    fats — fatty    acids    and 

Lipolytic 

Lipase 

Liver,  etc. 

glycerin 
Neutral    fats — fatty    acids    and 
glycerin 

Pepsin 

Gastric  juice 

Proteins — peptones  and  amino- 
acids 

Trypsin 

Pancreatic  juice 

Proteins — peptones  and  amino- 

Proteolytic 

acids 

Erepsin 

Small  intestine 

Proteoses — amino-acids 

Nuclease 

Pancreas,  spleen,  thymus,  etc. 

Nucleic  acid — purin  bases 

Entcrokinase 

Small  intestine 

Trypsinogen^trypsin 

Guanase 

Thymus,  adrenals  and  pancreas 

Guanin — xanthin 

Adenase 

Spleen,  pancreas  and  liver 

Adenin — hypoxanthin 

Deaminizing 

Deaminase 

Tissues 

Arginase 

Liver  and  spleen 

A  m  i  n  o-acids — oxyacids 
arginin — urea 

Oxidase 

Lungs,  liver  and  tissues 

Oxidizes  organic  substances 

Catalase 

Tissues 

Decomposes  hydrogen  peroxide 

Reductase 

Tissues 

Caiises  deoxidation 

Although  still  incomplete,  this  enumeration  proves  very  clearly 
that  almost  every  reaction  necessitates  the  presence  of  a  particular 
enzyme.  There  can  be  only  one  reason  for  this,  namely,  that  they  are 
specific  in  their  action  and  cannot  be  employed  interchangingly  to 
produce  one  and  the  same  result.  Thus,  pt3^alin  changes  starch  into 
maltose,  but  does  not  affect  the  fats  and  proteins,  nor  even  the  other 
carbohydrates.     Quite   similarly,   given   a   number  of   closely   allied 


990  DIGESTION 

substances,  such  as  the  disaccharides,  it  will  be  found  that  they  re- 
quire several  enzymes  to  convert  them  into  the  monosaccharides. 
Maltose  has  its  own  specific  enzyme  maltase,  and  lactose  a  similarly 
specific  enzyme  lactase.  We  also  note  that  a  single  secretion,  such  as 
the  pancreatic  juice,  may  harbor  a  number  of  ferments,  which  act  sepa- 
rately upon  different  foodstuffs.  To  be  sure,  this  specificity  is  also 
displayed  by  other  catalyzers,  but  not  quite  so  definitely  as  by  the 
enzymes.  Thus,  it  is  a  well-known  fact  that  the  oxidation  of  hydriodic 
acid  by  bromic  acid  may  be  effected  by  means  of  potassium  bichromate 
but  not  by  iodic  acid.  Quite  similarly,  the  oxidation  of  potassium 
iodid  by  potassium  persulphate  may  be  quickened  by  copper  salts, 
but  not   the  oxidation  of  sulphur  dioxid  by  potassium  persulphate. 

In  many  cases,  these  ferments  exist  within  the  cell  in  an  inactive 
form  and  do  not  unfold  their  characteristic  properties  until  they  have 
been  discharged  into  the  secretory  medium.  This  antecedent  body 
is  known  as  the  proferment  or  zymogen,  and  is  usually  stored  in  the 
form  of  granules.  Its  activation  may  be  accomplished  by  inorganic 
or  organic  means.  In  the  former  instance  the  intermediary  substance 
is  known  as  an  activator  and  the  latter  as  a  kinase.^ 

The  Manner  of  Action  of  the  Ferments. — Catalysis  is  a  common 
phenomenon  in  nature  and  many  chemical  means  and  substances  may 
be  employed  to  bring  it  about.  Thus,  the  disaccharides  may  be  made 
to  undergo  hydrolysis  into  the  monosaccharides  by  smiply  heating 
them  under  pressure  to  110°C.,  and  cane-sugar  may  be  inverted  into 
dextrose  and  levulose  by  the  addition  of  a  weak  acid.  Either  means 
serves  to  accelerate  the  reaction,  which  otherwise  would  not  take  place 
at  all  or  only  with  extreme  slowness.  It  is  for  this  reason  that  cata- 
lyzers have  been  compared  to  the  oil  by  means  of  which  machinery  may 
be  made  to  run  smoothly,  i.e.,  while  they  do  not  initiate  a  certain  proc- 
ess, they  are  in  a  position  to  vary  its  velocity.  Consequently,  the 
essential  difference  between  ordinary  catalyzing  agents  and  ferments 
lies  in  the  fact  that  the  latter  effect  catalysis  much  more  rapidly  at 
moderate  temperatures  and  impart  to  it  a  more  specific  character.  In 
analogy  with  ordinary  catalyzing  agents  the  ferjnents  may  cause: 

(a)  Hydrolysis. — This  change  involves  a  taking  up  of  water  and  a  conversion  of 
the  substance  into  simpler  molecules.  As  an  example  of  this  process  might  be 
mentioned  the  decomposition  of  the  disaccharides,  such  as  maltose,  into  monosac- 
charides, one  molecule  of  water  being  taken  up  and  two  molecules  of  the  latter 
substance  being  produced.  The  conversion  of  fats  into  fatty  acids  and  glycerin 
requires  three  molecules  of  water.  The  reverse  process  is  dehydration.  As  an 
example  of  this  kind  might  be  mentioned  the  building  up  of  the  amino-acids  into 
polypeptides  and  the  complex  proteins  of  the  cells. 

(5)  Deamination. — Many  tissues  possess  the  power  of  splitting  off  an  NH3 
group  from  amino-acid  as  ammonia  and  replacing  it  by  H  or  OH.  The  reverse 
process  is  continuously  going  on  in  jilants  which  synthetize  proteins  from  ammonia 
and  a  carbohydrate.  Some  evidence  is  also  at  hand  to  show  that  this  reversion 
may  be  effected  by  animals. 

(c)  Decarboxylation. — This  process  involves  the  loss  of  a  molecule  of  carbon  di- 

1  Samuely,  Handb.  der  Biochemie,  1908. 


THE    CHEMISTRY    OF    DIGESTION  991 

oxide  from  amino-acids  aiul  thi'ir  convi-nsiuii  into  tlu;  ourrcspondiiiK  amino.  This 
change  is  coniinonly  produced  by  bacterial  action,  but  may  also  take  place  normally 
as  a  step  in  the  oxitlation  of  the  carbon  atonis  in  the  carl)ohydrates  and  long  chain 
fatty  acids. 

(J)  Oxidalion  and  Reduction. — This  process  consists  in  the  successive  conversion 
of  substances  into  COo  and  water  under  an  evolution  of  energy  which  is  much  greater 
than  that  derived  from  the  changes  enumerated  previously. 

One  of  the  important  deductions  to  be  derived  from  this  tabulation 
is  that  catalyzers  and  especially  ferments,  not  only  accelerate  decompo- 
sitions, but  are  also  instrumental  in  reforming  the  original  sul^stance 
from  its  simple  end-products.  This  phenomenon  which  is  known  as 
rcrersihility,  was  first  shown  to  take  place  by  Croft  Hill^  in  two  experi- 
ments with  sucrose  and  invertase.  An  especially  good  example  of  such 
a  reversible  action  has  been  furnished  by  Kastle  and  Loevenhart.^ 
By  employing  the  simple  ester  ethyl-butyrate,  they  were  able  to  prove 
that  lipase  not  only  hydrolyzcs  this  substance  into  ethyl-alcohol  and 
butyric  acid,  but  also  synthetizes  these  products  of  hydrolysis  into 
ethyl-butyrate  and  water.  It  appears,  therefore,  that  one  and  the 
same  enz3Tne  may  serve  not  only  to  split  a  foodstuff  into  its  simple 
constituents,  but  also  to  reconstruct  the  latter  into  a  more  complex 
substance  while  they  traverse  the  lining  of  the  intestine  or  enter  the 
tissues.  Some  investigators  assert  that  this  reversibility  is  something 
more  than  a  mere  establishment  of  an  equilibrium  and  conforms  closely 
to  a  true  synthesis  (Bertrand). 

It  is  also  to  be  noted  that  ferments  act  best  at  an  optimum  tempera- 
ture of  40°  to  50°C.  While  this  is  true  of  all  catalyzers,  ferments  seem 
to  have  a  more  restricted  sphere,  low  and  high  temperatures  being 
detrimental  to  them.  At  60°  to  80°C.,  they  lose  their  power,  and  are 
destroyed  absolutely  at  100°C.  It  is  also  apparent  that  the  action  of 
catalyzing  agents  increases  with  their  surface.  An  analogous  process 
is  presented  bj^  the  condensation  of  a  gas  upon  a  soHd  surface  or  by  the 
combination  of  hydrogen  and  oxygen  bj^  means  of  finely  subdivided 
platinum.  In  addition,  it  has  been  assumed  that  the  unusual  power 
of  ferments  is  due  to  their  abilitj^  of  forming  certain  intermediate 
products  which,  although  they  do  not  energize  the  reaction  itself, 
serve  as  a  means  of  attaining  the  end-stage  of  the  catalj^sis  more 
rapidly.  As  a  last  factor  influencing  ferment  action  might  be  men- 
tioned the  number  of  ferment-molecules  involved.  Thus,  it  has  been 
found  that  the  degree  of  the  change  effected  in  a  given  period  of  time, 
is  proportional  to  the  amount  of  the  ferment  engaged  in  this  process, 
and  is  in  a  measure  independent  of  the  concentration  of  the  substra- 
tum. It  should  be  remembered,  however,  that  ferments  act  in  infin- 
itesimally  small  quantities,  and  that  an  abundant  supply  of  them  is 
rather  deleterious  to  the  reaction.  The  reason  for  this  diminution  in 
the  effectiveness  of  a  ferment,  when  present  in  large  amounts,  is  not 

1  Brit.  Med.  Jour.,  190.3,  also  Mathews  and  Glenn,  Jour.  Biol.  Chem.,  ix.  1911. 
29. 

2  Am.  Jour,  of  Physiol.,  vi,  1902,  331. 


992  DIGESTION 

easily  understood,  unless  it  is  assumed  that  the  enzyme  then  destroys 
itself  in  part  by  autolysis.  But  this  retardation  does  not  take  place 
under  all  circumstances,  because  certain  fermentations  which  have 
come  to  a  standstill  owing  to  the  large  amounts  of  ferment  present, 
may  again  be  brought  under  way  by  diluting  the  mixture  or  by  remov- 
ing the  products  formed  in  the  course  of  the  reaction. 

This  "self-inhibition"  is  closety  allied  to  the  inhibition  of  ferment 
action  by  outside  means.  ^  Thus,  it  is  a  well-known  fact  that  these  proc- 
esses may  be  greatly  retarded  and  abolished  by  strong  acids,  alkalies, 
alcohol,  iodin,  potassium  cyanide,  formaldehyde,  and  the  salts  of  the 
hea\'y  metals.  In  many  instances,  the  cells  of  the  different  tissues 
produce  a  substance  which  is  called  anti-enzyme.  For  example,  if 
an  enzjTiie  is  injected  into  the  blood-stream,  certain  cells  are  stimu- 
lated to  produce  an  anti-enzyme  of  a  specific  kind,  so  that  the  serum  of 
this  blood  may  be  mixed  with  the  original  enzj-me  with  the  result  that 
the  latter  is  then  quite  unable  to  unfold  its  characteristic  action. 

As  to  the  manner  in  which  enzymes  increase  the  velocity  of  the  re- 
action to  w^hich  they  are  specificall}'  assigned,  few  positive  statements 
can  be  made.  In  the  first  place,  it  may  be  assumed  that  the  ferment  is 
combined  with  the  substrate  in  a  loose  manner — fitted  to  it  as  a  kej^  in 
its  corresponding  lock.^  This  simile,  no  doubt,  calls  to  our  minds  the 
interaction  between  the  antigen  and  the  immune  bodies,  as  explained 
by  the  side  chain  theory  of  Ehrlich.  In  the  second  place,  it  is  evi- 
dent that  the  ferment  is  finally  removed  from  the  sphere  of  its  action 
and  enters  the  end-products.  This  brings  the  catalysis  to  an  end. 
These  reactions,  however,  are  different  from  those  taking  place  between 
various  inorganic  substances,  because  the  latter  are  chiefly  interac- 
tions between  electrolytes.  Thus,  the  molecules  of  sodium  chlorid 
are  broken  up  into  their  cations  Na  which  are  charged  positively  and 
move  toward  the  cathode  or  negative  pole,  and  their  anions  CI  which 
are  negative  and  move  toward  the  anode  or  positive  pole.  Since  the 
organic  foodstuffs,  namely,  the  proteins,  carbohydrates  and  fats,  are 
not  electrolytes,  their  reactions  cannot  be  regarded  as  analogous  to 
these  ahnost  instantaneous  ionic  movements.  They  take  place  more 
slowly  and  are  in  realitj'  molecular  interactions.  When  only  one 
substance  is  being  transformed,  it  constitutes  a  unimolecular  reaction. 
As  an  example  of  this  kind  might  be  mentioned  the  conversion  of 
starch  into  sugar.  The  velocity  of  the  reaction  is  measured  in  this 
case  in  terms  of  substance  transformed,  i.e.,  in  gram-molecules  per 
liter  in  the  unit-time  of  one  minute.  But,  as  the  amount  of  substance 
acted  upon  is  gradually  diminished,  the  velocity  of  the  reaction  must 
also  be  reduced  in  a  proportionate  measure.  In  those  cases  in  which 
two  substances  are  changed  simultaneously,  as  occurs  in  the  decompo- 
sition of  esters  under  the  influence  of  an  alkali,  a  himolecular  reaction 

1  Porter,  Quart.  Jour,  of  Exp.  Physiol.,  iii,   1910,  375.^ 

2  Emil  Fischer,  Zeitschr.  fiir  physiol.  Chemie,  1898. 


THE    CHEMISTRY    OF    DIGESTION  993 

taki's  plact'.     The  velocity  of  tlir  reaction  is  then  i^ropoitioiuil  to  the 
square  of  the  amount  of  the  substance. 

The  Function  of  Saliva. — Saliva  possesses  a  two-fold  action,  namely, 
a  physical  one  and  a  chenucal  one.  It  moistens  the  mucous  surfaces 
of  the  mouth  as  well  as  the  food,  thereby  facilitatinji;  its  mastication  and 
deglutition.  In  addition,  it  acts  as  a  solvent  allowing  sapid  substances 
to  excite  sensations  of  taste,  and  as  a  cleaning  agent  of  the  oral  cavity. 
The  former  is  of  special  importance,  because  it  sei-ves  to  evoke  those 
stinuili  which  give  rise  to  the  psychic  secretion  of  gastric  juice  and  a 
certain  satisfaction  in  eating.  These  are  its  only  functions  in  those 
animals,  such  as  the  horse,  sheep,  ox  and  dog,  in  which  a  true  digestive 
ferment  is  not  present.^  The  substance  more  particularly  concerned 
in  this  purely  mechanical  process  is  mucin.  In  man  and  some  of  the 
herbivora,  however,  it  also  possesses  a  moderate  chemical  action  by 
virtue  of  its  enzyme  ptyalin.  This  ferment  acts  exclusively  upon 
starch,  converting  it  into  maltose  through  several  intermediary  stages, 
such  as  soluble  starch  or  erythro-dextrin  which  gives  a  red  color  with 
iodin,  and  achroo-dextrin  which  gives  no  color  with  iodin.  But  since 
ptyalin  does  not  attack  cellulose,  it  is  imperative  that  the  starch  be 
well  cooked  beforehand  so  as  to  destroy  its  capsular  investments. 
Moreover,  W'hile  the  warmth  of  the  mouth  causes  the  starch  to  be  re- 
duced very  rapidly,  a  considerable  portion  of  even  the  boiled  starch 
invariabl}^  escapes  salivary  digestion,  because  mastication  is  usually 
practised  in  a  hasty  and  careless  manner.  The  solid  starch  which  is 
ingested  in  farinaceous  foods,  bread,  and  biscuits,  is  only  slightly 
affected  by  the  saliva  and  practically  no  hydrolysis  is  instituted  by 
this  secretion. 

Ptyalin  is  most  effective  at  37°C.  and  in  a  neutral  or  weak  acid 
medium,  but  a  slightly  alkaline  medium  is  not  unfavorable  to  its 
activity.  Inasmuch  as  its  action  is  destroyed  by  such  small  amounts 
of  acid  as  0.003  per  cent.  HCl,  it  might  be  supposed  that  it  must  lose 
its  effectiveness  as  soon  as  it  enters  the  stomach.  This  is  not  the  case, 
because  the  freshly  swallowed  food  forms  a  coherent  mass  which  is  not 
easily  penetrated  by  the  gastric  juice,  and  besides,  some  time  must 
elapse  before  a  sufficient  quantity  of  the  latter  has  been  secreted  to  fill 
the  relativel}'  inactive  cardiac  end  of  the  stomach.  During  the  interim, 
the  ptyaHn  continues  its  reductions  and  it  is  safe  to  say  that  from  30  to 
40  minutes  must  elapse  before  its  action  is  stopped  completely.  Mean- 
while, the  largest  part  of  the  available  starch  has  been  hydrolyzed  and, 
while  a  certain  proportion  of  unreduced  starch  may  escape  salivary 
digestion,  it  is  later  on  subjected  to  the  action  of  the  amylopsin  of  the 
pancreatic  juice.  Unboiled  starch,  on  the  other  hand,  escapes  even 
this  powerful  diastatic  ferment  and  enters  the  feces  unutilized. 

The  Function  of  Gastric  Juice. — The  action  of  the  gastric  juice 
is  due  partly  to  its  acid  and  partly  to  the  combined  action  of  its  acid 
and  ferments.     It  may  be  said  that: 

iKuss,    Ref.    Maly,    1898,    Zebrowski,    Pfluger's  Archiv,  ex,    1905,    105,   and 
Palmer,  Am.  Jour,  of  Physiol.,  xli,  1916,  483. 
63 


994  DIGESTION 

(a)  It  is  Antiseptic. — Whenever  carbohydrates  are  ingested,  a  certain  number 
of  micro-organisms  are  also  taken  in.  These  give  rise  to  fermentations,  in  the 
course  of  which  considerable  quantities  of  lactic  acid  may  be  produced.  The 
subsequent  outpouring  of  hydrochloric  acid  destroys  many  of  these  organisms, 
as  well  as  others  of  pathogenic  character,  but  some  of  them  always  escape  into  the 
intestine  (bac.  acidi  lactici),  where  they  find  a  more  suitable  medium  for  their 
growth. 

(b)  It  Inverts  Sucrose  into  Glucose  and  Fructose. — This  action  is  not  due  to  the 
presence  of  an  invertase  in  this  juice,  but  to  the  hydrochloric  acid  and  such  invert- 
ing enzymes  as  may  be  present  in  the  food  ingested.* 

(c)  It  contains  a  Jal-splitting  enzyme  or  lipase.  Its  action  in  this  regard  is  two- 
fold, because  the  hydrochloric-pepsin  combination  dissolves  the  protein  constitu- 
ents and  investments  of  the  fat-cells,  and  allows  the  fat  to  escape  and  to  coalesce. 
In  addition,  a  small  quantity  of  lipase  is  present  which  splits  the  emulsified  fat 
into  glycerol  and  fatty  acids,  but  naturally,  the  hydrolysis  going  on  in  this  organ 
is  insignificant  when  compared  with  that  effected  in  the  intestine  by  the  pan- 
creatic juice.  The  origin  of  this  lipase  is  somewhat  in  doubt;  some  claim  that 
it  is  regurgitated  with  the  contents  of  the  small  intestine  and  some,  that  it  is  an 
actual  product  of  the  gastric  mucosa.  It  is  of  much  greater  importance  to  the 
suckling  than  to  the  adult. 

{d)  It  Curdles  Milk. — This  property  of  gastric  juice  is  due  to  its  ferment 
rennin  or  chymosin-  which,  as  has  been  mentioned  above,  appears  to  be  formed 
separately  from  the  pepsin. ^  It  initiates  a  two-fold  proce.ss,  namely,  the  conversion 
of  caseinogen  into  casein,  and  the  combination  of  the  altered  casein  with  the 
soluble  calcium  salts  to  form  a  curd.^  This  action  is  greatly  accelerated  by  the 
hydrochloric  acid  which  in  it.self  Ls  capable  of  precipitating  caseinogen,  but  this  acid 
is  by  no  meaiLS  an  indispensable  factor  as  is  pro\nded  by  the  fact  that  the  curdUng  of 
milk  also  takes  place  in  a  neutral  or  alkaline  medium,  but  not  after  the  milk  has 
been  boiled.  Moreover,  the  curd  produced  by  rennin  in  the  presence  of  calcium 
salts,  exhibits  certain  properties  which  are  quite  different  from  those  exhibited  by 
the  acid  precipitate.  At  all  events,  the  newly  formed  casein  is  subjected  later  on 
to  the  action  of  pepsin  in  the  same  waj'  as  other  proteins.  It  seems,  however, 
that  the  curdling  of  milk  takes  place  before  much  acid  has  been  secreted;  in  fact, 
milk  is  not  an  effective  stimulant  for  the  secretion  of  hydrochloric  acid,  and  is  used, 
therefore,  to  allay  hyperchlorhydria.  To  the  suckling,  the  curd  is  of  profound 
importance,  because  it  tends  to  retain  this  important  nutritive  material  for  a  longer 
time  in  the  stomach  so  that  it  may  undergo  thorough  digestion.^ 

(e)  It  contains  a  proteolytic  enzyme.  This  is  its  most  important  property.  The 
combination  of  pepsin  and  hydrochloric  acid  converts  the  proteins  of  the  food  into 
peptones,  but  does  not  change  their  constituent  polypeptides  into  their  ultimate 
cleavage  products,  the  amino-acids.  This  change  is  effected  Viy  hj^drolysis,  the 
first  stage  being  the  formation  of  acid  meta-protein,  and  the  next  step,  the  forma- 
tion of  proteoses,  such  as  albumoses,  globuloses,  vitelloses,  etc.,  as  follows: 

Protein 

Acid  meta-protein 

■r,  ■  '  Proteo-proteose 

Propeptone  or  proteose  [  Hctero-proteose 


Peptone  or  polypeptides 


Secondary.    Deutero-proteose 


^  Widdicombe,  Jour,  of  Physiol.,  xxviii,  1902,  17.5. 
^  Hammersten,  Maly's  .Jahresb.,  1872. 
^  Porter,  Jour,  of  Physiol.,  xlii,  1911,  389. 

*  Van  Slyke,  New  York  Med.  Jour.,  1909,  Proc,  Soc.  Exp.  Biol,  and  Med., 
1911. 

s  GmeUn,  Pfliiger's  Archiv,  ciii,  1904,  618. 


THE    CHEMISTRY    OF    DIGESTION 


995 


Proteoses  and  peptones  arc  classified  in  accordance  vvitli  their  physical  character- 
istics, such  as  their  solubility  and  salting  out.  In  the  followiiif!;  table  a  native 
protein  albumin  is  contrasted  in  this  respect  with  its  peptic  end-products: 

A(^li<)n  of 


Heat 

Aixnhni                  Nitric              Ammonium 
Alcohol                   ^^jj                  sulphate 

Copper 
sulphate 

Diffuai- 
bUity 

Albumin 

C  o  a  g  u  1  a  - 
tion 

Precipita- 
tion   and 
c  o  a  g  u  1  a- 
tion. 

1 
Precipita-  Precipita- 
tion in  the     tion     after 
cold;     not      complete 
easilj'    dis-     saturation 
solved    on 
heating 

Violet 
color 

Xone 

Proteo- 
ses 

No  coagula- 
tion 

Precipita- 
tion, but 
no  coagula- 
tion 

Precipita- 
tion in  the 
cold ;  easily 
dissolved 
on  heating 

Precipita-  Rose  red  Slight 
tion     after      color 
saturation 

Peptones 

No  coagula- 
tion 

Precipita- 
tion but  no 
coagulation 

No   precipi- 
tation 

No  precipi-l  Rose  red  Readily 

tation          1    color 

Upon  the  constituents  of  connective  tissue  and  other  allied  protein  substances, 
the  pepsin-hydrochloric  acid  combination  acts  as  follows: 

(a)  Collagen,  a  constituent  of  bone  and  white  fibrous  and  areolar  tissue,  is 
converted  into  gelatin,  gelatoses  and  gelatin-peptones.  Since  these  tissues  con- 
tain much  fat,  this  foodstuff  is  separated  from  its  investments. 

(6)  Elastin,  a  constituent  of  elastic  tissue,  is  not  acted  upon  under  ordinary 
conditions. 

(c)  Mucin,  a  constituent  of  the  ground-substance  of  connective  tissue,  is  con- 
verted into  peptone-like  substances. 

(d)  Nucleo-proteins  are  changed  into  a  protein  portion  and  a  nuclein  portion. 
The  former  is  then  converted  into  proteoses  and  peptones,  whereas  the  latter  is 
precipitated  in  an  insoluble  form.  On  phospho-proteins  it  acts  in  a  somewhat  simi- 
lar manner. 

The  Function  of  Pancreatic  Juice. — This  secretion  plays  an  even 
more  important  part  in  digestion  than  the  gastric  juice,  because  it 
contains  several  powerful  enzymes.  Its  function  may  be  summarized 
as  follows: 

(a)  Proteolytic. — This  property  is  imparted  to  it  by  its  enzyme  trypsin  which 
differs  materially  from  pepsin,  because  it  gives  rise  to  a  more  rapid  as  well  as  more 
thorough  catalysis.  To  begin  with,  it  is  to  be  noted  that  trypsin  acts  in  an  alka- 
line medium,  whereas  pepsin  acts  in  an  acid  medium.  Moreover,  while  the  former 
produces  the  same  initial  conversions  of  the  protein  molecule  as  the  latter,  it  does 
not  stop  here  but  reduces  the  peptones  still  further  into  their  constituent  amino- 
acids,  such  as  leucine,  tyrosine,  alanine,  aspartic  acid,  glutamic  acid,  arginine, 
tryptophane,  and  others.  It  is  also  to  be  observed  that  this  conversion  is  effected 
so  rapidly  that  the  formation  of  the  primary  proteoses  can  scarcely  be  detected, 
while  the  secondary  derivatives  come  into  prominence  almost  immediately.  In 
place  of  acid-metaprotein,  however,  we  now  obtain  alkaline-metaprotein.  In 
addition,  a  reduction  of  elastin  takes  place  which  is  not  effected  at  all  by  the  gastric 


996  DIGESTION 

juice.  "\Mien  the  peptone  stage  has  been  passed,  the  biuret  reaction  is  no  longer 
obtained.  Regarding  the  degree  of  alkahnity  existing  in  the  duodenum  much 
uncertainty  prevails.  While  pancreatic  juice  is  a  strongly  alkaline  secretion, 
owing  to  its  content  in  sodium  carbonate,  it  must  be  remembered  that  the  alkalin- 
ity of  this  medium  must  be  changed  repeatedl}'  by  the  entrance  of  the  fresh  acid 
chyme.  Its  reaction  maj^  then  become  neutral,  but  the  action  of  trypsin  cannot 
be  unfavorablj'  affected  by  a  condition  of  this  kind,  because  most  effective  artificial 
media  are  usually  made  by  dissolving  commercial  trypsin  in  only  0.2  to  0..3  per  cent, 
of  sodium  carbonate.  It  is  true,  however,  that  larger  amounts  of  this  enzyme 
require  a  larger  amount  of  this  salt.  It  has  been  pointed  out  above  that  the  con- 
version of  trypsinogen  into  trypsin  necessitates  the  presence  of  enterokinase  or  cal- 
cium salts.i  It  is  also  said  that  erepsin  may  be  present  at  times  in  pancreatic  juice, 
because  when  inactivated,  this  secretion  maj^  digest  casein  but  not  other  proteins. 

(b)  Amylohjtic. — Pancreatic  juice  contains  an  amylase,  known  as  amylopsin, 
which  hydrolyses  the  starches  more  rapidly  than  ptyalin.  Even  unboiled  starch 
is  affected  by  it  under  formation  of  erythro-dextrin  and  maltose.  In  a  nearly 
neutral  medium  this  disaccharide  is  converted  further  into  the  monosaccharide 
dextrose  or  glucose.  This  additional  hydrolysis  is  dependent  upon  the  presence 
of  a  second  ferment,  maltase. 

(c)  Lipolytic.^ — The  powerful  fat -splitting  enzyme  of  pancreatic  juice  is" 
called  steapsin.  It  changes  neutral  fats,  such  as  the  triglycerides  of  palmitic, 
stearic  and  oleic  acids,  into  the  corresponding  fatty  acids.  Since  this  medium  pos- 
sesses an  alkaline  reaction,  these  fatty  acids  unite  with  the  alkaline  bases  to  form 
soaps  which  then  appear  as  films  upon  the  outer  surfaces  of  the  fat-globules  and 
prevent  them  from  coalescing.  These  emulsions  assume  a  more  stable  character 
in  the  presence  of  proteins,  and  colloids. 

(d)  Milk-curdling.^ — Pancreatic  juice  also  possesses  the  power  of  clotting 
milk,  but  this  action  may  not  be  due  to  the  presence  of  a  special  enzyme.  It  differs 
in  its  character  from  that  of  rennin. 

The  Function  of  Bile. — The  velocity  with  which  lipolysis  takes 
place  in  the  small  intestine,  is  considerably  increased  by  the  presence 
of  bile,  the  active  agent  concerned  in  this  process  being  the  bile  salts. 
These  act  in  two  ways,  namelj^  bj^  theii*  solvent  action  on  fatty  acids 
and  soaps  and  secondly,  by  their  property  of  diminishing  the  surface 
tension  between  the  fat  and  the  water.  This  enables  the  intestinal 
juices  to  enter  into  closer  relation  with  the  globules  of  fat.  Con- 
sequently, the  digestive  value  of  bile  lies  in  its  adjuvant  power  of 
furnishing  a  more  appropriate  medimn  for  the  interaction  between  the 
steapsin  and  the  fatty  acids  than  the  pancreatic  juice  alone  could 
possibly  constitute.  In  some  animals,  it  also  contains  a  weak  amyloly- 
tic  enzyme. 

Bile  also  serves  as  a  vehicle  for  the  fats  during  their  absorption. 
This  statement  implies  that  the  end-products  of  lipolysis  traverse 
the  intestinal  epithelimn  not  merely  in  an  emulsified  form,  but  as  fatty 
acids  or  soaps  and  glycerin.  This  gives  rise  to  a  "circulation  of  the 
bile,"  because  some  of  the  biliary  substances  are  again  absorbed  and 
made  use  of  later  on  in  the  manner  just  indicated. 

While  the  bile  salts  possess  mild  antiseptic  qualities,  the  bile  itself 

'  Schepowalnikow,  Dissertation,  St.  Petersburgh,  1899,  and  Bayliss  and  Star- 
ling, Jour,  of  Phj-siol.,  xxviii,  1902,  375. 

2  Connstein,  Ergebn.  der  Physiol.,  iii,  1904. 

'  Kiihne  Verh.,  med.  Verein,  Heidelberg,  iii,  1881. 


THE    CHEMISTRY    OF    DIGESTION  997 

has  no  definite  influence  of  this  kind.  In  other  words,  the  fact  that  it 
dhuiiiishes  putrefaction  in  the  intestine,  is  (hie  chiefly  to  its  power  of 
hastening  the  absorption  of  those  sul)stances  which  arc  most  Hkely 
to  give  rise  to  these  processes.  Bile  is  to  a  certain  extent  excretory. 
In  addition,  it  aids  in  neutrahzing  the  acid  chyme  and  in  precipitat- 
ing its  unpeptonized  protein.  This  renders  the  chyme  more  viscid 
and  retards  its  progress  tlirough  the  intestine,  thereby  augmenting 
absorption. 

The  Function  of  the  Intestinal  Juice. — The  principal  action  of  the 
intestinal  secretion  is  exerted  upon  the  carbohydrates.  Its  invertase 
changes  cane-sugar  into  glucose  and  levulose  or  fructose,  whereas  its 
maltase^  transforms  maltose  into  glucose. ^  A  special  enzyme,  called 
lactase,^  is  abundantly  present  in  young  animals  for  the  purpose  of 
converting  milk-sugar  into  galactose  and  glucose.  The  ferment 
enterokinasc  (Pawlow)  which  activates  trypsinogen,  is  widely  distrib- 
uted through  the  intestine.  A  similar  body  is  erepsin'*  which  increases 
the  hydrolysis  of  the  first  products  of  the  proteolysis  and  rapidly  changes 
albumoses  and  peptones  into  amino-  and  diamino-acids.  Moreover, 
since  a  great  deal  of  fat  may  be  split  up  in  the  small  intestine 
even  in  the  absence  of  both  bile  and  pancreatic  juice,  it  is  assumed  that 
it  contains  a  lipase  of  relatively  feeble  power.  The  sodium  carbonate, 
in  which  it  is  rather  rich,  must,  of  course,  aid  in  the  formation  of  soaps 
from  the  fatty  acids. 

This  fact  brings  up  the  important  point  that  the  secretions  in  the 
intestine  form  a  suitable  medium  for  the  growth  of  bacteria,  contrary 
to  the  gastric  juice  w^hich  by  virtue  of  its  acidity  attenuates  micro- 
organisms. Some  of  them,  however,  reach  the  intestine  in  spite  of 
the  gastric  juice  and  produce  here  certain  enzjmies,  the  actions  of 
which  are  very  similar  to  those  of  the  ferments  normally  contained 
in  the  local  secretions.  In  some  instances,  these  putrefactive  organ- 
isms also  give  rise  to  more  specific  reactions,  as  follows: 

(a)  On  Carbohydrates. — The  most  important  reaction  is  the  lactic  acid  fermenta- 
tion which  is  chiefly  responsible  for  the  formation  of  intestinal  gases.  It  usually 
takes  place  in  two  stages  which  may  be  represented  by  the  following  two  equations : 

Ci2H220n   +  H2O    =  4C3H6O3 

(Lactose)  (Lactic  acid) 

4C3H6O3  =  2C4H8O2  +  4CO2  +  4Ho 
(Lactic  acid)  (Butyric  acid) 

Vegetable  food  increases  this  fermentation,  the  cellulose  being  split  into  carbonic 
acid  and  urethane. 

(6)  On  Fats. — Some  bacteria  possess  a  lipolytic  action  and  are  capable  of  pro- 
ducing lower  acids,  such  as  valeric  and  butyric.     It  cannot  surprise  us,  therefore, 

^  Rosenbloom,  Conn.  Biolog.  Chem.,  xiv,  1913,  241,  and  Hammarsten, 
Ergebn.  der  Physiol.,  1905. 

2  Rohmann,  Pfltiger's  Archiv,  xli,  1887,  424. 

3  Halliburton,  Textb.  of  Chem.  Path,  and  Physiol.,  1891. 

*  Cohnhein,  Zeitschr.  fiir  phys.  Chemie,  xxxvi,  1902,  13,  and  Vernon,  Jour,  of 
Physiol.,  xxxii,  1904,  32. 


998  DIGESTION 

to  find  that  the  contents  of  the  lower  small  intestine  may  become  acid,  in  fact,  this 
acidity  may  on  occasions  invade  higher  segments  without,  however,  materially 
impairing  i)ancrcatic  digestion.  The  latter,  as  we  have  seen,  does  not  require  an 
especially  high  alkalinity. 

(c)  On  Proteins. — Some  bacteria  are  capable  of  splitting  proteins  into  amino- 
acids,  liberating  during  this  process  such  substances  as  indol  (CsHyN),  scatol 
(CgHgN),  and  phenol  (CbHgO).  These  animo-acids  are  further  reduced  by  them 
into  their  corresponding  amine  bases  by  the  process  of  decarboxylation  which  con- 
sists in  removing  carbon  dioxid  from  their  carboxyl  (COOH)  group.  In  this  way, 
leucine  may  be  converted  into  its  base  iso-amylamine,  as  follows: 

gg^^CHCH.CHNHrCOOH  =  gg^^CHCHaCHsNHj  +  CO2 

This  base,  and  especially  the  oxyphenylethylamine  derived  from 
tyramine,  possesses  a  pressor  action  similar  to  that  of  adrenalin. 
The  former  substance  is  a  constituent  of  ergot.  It  is  also  of  interest 
to  note  that  the  enzymes  of  fungi,  such  as  those  affecting  grasses  and 
fruits,  are  capable  of  decarboxylizing  some  of  these  bases.  In  spite 
of  the  formation  of  the  aforesaid  acids,  however,  the  contents  of  the 
large  intestine  become  alkaline.  This  change  is  due  to  the  fact  that 
some  of  the  bacteria  generate  ammonia  which  again  neutralizes  the 
organic  acids. 


CHAPTER  LXXXIV 

THE  MECHANICS  OF  DIGESTION 

A.  MASTICATION  AND  DEGLUTITION 

General  Consideration. — In  those  animals  in  which  digestion  is 
chiefly  intracellular,  the  chemical  processes  necessitate  a  mechanical 
manipulation  of  the  food  which  purposes  to  effect  its  reduction  into 
smaller  masses  and  its  steady  onward  movement,  so  that  it  may  be 
successively  subjected  to  the  different  secretions.  Leaving  out  of 
consideration  the  celenterata,  in  which  the  digestive  and  vascular 
systems  are  still  incompletely  separated,  as  well  as  the  echinodermata, 
in  which  this  separation  is  complete,  it  may  be  said  that  the  arth- 
ropoda  are  the  first  to  present  an  alimentary  canal  which  shows 
definite  variations  in  its  caliber,  corresponding  to  the  stomach,  and 
small  and  large  intestines  of  the  higher  animals.  Glandular  organs 
are  placed  along  this  canal  which  seem  to  be  homologous  with  the 
salivary  glands  and  the  liver-pancreas  of  the  higher  forms.  Possibly 
the  simplest  alimentary  system  among  the  vertebrates  is  presented 
by  the  fishes.  It  consists  of  a  stomach,  the  glands  of  which  furnish 
an  acid  proteolytic  secretion,  and  a  fully  differentiated  intestine  with 
a  series  of  digestive  fhiids  possessing  different  actions. 

The  alimentary  canal  of  birds  exhibits  several  peculiarities,  such  as 


TIU';    MECHANICS    OF    DIGESTION  999 

the  crop  and  the  double  stoinacli.  Tlic  foniicr  appears  as  an  enlarge- 
ment of  the  proximal  segment  of  I  lie  eso])hafi;us,  and  serves  as  a 
reservoir  for  the  food,  peiformiiiji;  a  function  similar  to  that  of  the  oral 
pockets  of  the  scjuirrels  and  alhed  aniuuds.  liesidcs,  tiiis  i)ro-stomach 
furnishes  a  secretion  which  institutes  a  swelling  of  the  kernels  and  a 
destruction  of  their  cellulose  investments.  Of  special  interest  is  the 
fact  that  this  organ  also  secretes  a  milk-like  fluid  which  serves  as  food 
for  the  young  during  tiie  first  two  or  three  weeks  of  their  life.  It 
contains  a  considerable  amount  of  fat  which  is  derived  from  the  des- 
quamated and  degenerated  epithelial  lining.  The  stomach  of  these 
animals  consists  of  two  segments,  namely,  a  glandular  pro-ventriculus, 
and  a  muscular  ventriculus.  The  former  furnishes  an  acid  secretion 
rich  in  pepsin,  whereas  the  latter  reduces  the  food  into  smaller  frag- 
ments. In  this  function  it  is  aided  very  materially  by  the  solid  sub- 
stances, such  as  granules  of  sand,  which  these  animals  are  in  the 
habit  of  ingesting  with  their  food. 

The  alimentary  canal  of  the  mammals  presents  as  its  two  principal 
characteristics  the  division  of  the  stomach  into  two  or  four  cavities, 
and  the  varying  length  and  caliber  of  the  small  and  large  intestines. 
The  carnivora  are  characterized  by  a  preponderance  of  the  small 
intestine,  and  the  herbivora  by  a  preponderance  of  the  large  intestine. 
Some  of  the  mammals,  such  as  the  rodents  and  cetaceae,  are  in  possession 
of  a  stomach  consisting  of  two  pouches,  while  that  of  the  ruminating 
animals  consists  of  four  compartments.  In  the  latter,  the  esophagus 
terminates  in  a  vestibular  enlargement  which  communicates  with  the 
first  and  second  gastric  cavities.  The  food  enters  chiefly  the  first 
cavity,  where  it  is  intei  mingled  with  older  material  and  is  in  part 
forced  into  the  second  compartment.  After  30  to  70  minutes  (cow), 
small  amounts  of  the  now  somewhat  softened  material  are  projected 
into  the  mouth  to  be  remasticated.  Most  of  this  material  is  finally 
converted  into  a  liquid  mass  which  upon  being  reswallowed  is  directed 
into  a  muscular  furrow  through  which  it  attains  the  third  and  fourth 
cavities.  Its  still  unreduced  portion  is  retained  in  the  first  compart- 
ment to  be  remasticated  if  necessary  at  the  rate  of  6  to  8  times  in  the 
course  of  24  hours,  each  act  of  mastication  lasting  from  45  to  60  min- 
utes. Liquids,  on  the  other  hand,  may  enter  all  four  compartments 
simultaneously.  The  capacity  of  the  cow's  stomach  varies  between 
160  and  230  liters,  four-fifths  of  which  are  apportioned  to  the  first 
two  chambers. 

The  alimentary  canal  contains  secretory  as  well  as  muscular  ele- 
ments which  are  held  together  by  varying  amounts  of  connective  tissue. 
Its  length  varies  considerably  in  different  animals,  being  shortest  in 
the  carnivora  and  longest  in  the  herbivora.  In  general,  the  ratio 
between  its  length  and  that  of  the  entire  body  is,  in  man,  as  1  :  5  or  1  : 6; 
in  the  dog,  as  1:6;  in  the  cat,  as  1  : 4;  in  the  cow,  as  1  :20,  and  in  the 
sheep,  as  1  :27.  The  mucous  membrane  lining  the  digestive  tract 
presents   a   surprisingly  large   surface   to   the   simplified   foodstuffs. 


1000  DIGESTION 

Thus,  it  has  been  ascertained  that  the  mucosa  of  the  dog,  if  spread  out 
in  a  single  layer,   covers  more  than  one-half  of  the  body-surface. 

In  man,  the  muscular  stratum  of  the  alimentary  canal  is  made  up  of 
smooth  muscle  tissue  which  is  arranged  in  two  layers,  an  outer  longi- 
tudinal and  an  inner  circular.  This  arrangement  is  departed  from  in 
the  mouth,  pharynx  and  stomach,  where  oblique  fibers  are  added; 
moreover,  the  mouth,  pharynx,  upper  part  of  the  esophagus,  and  end 
of  the  rectum,  contain  numerous  strands  of  striated  muscle.  Inter- 
nally, the  circular  layer  of  smooth  muscle  tissue  lies  in  relation  with 
areolar  tissue,  containing  blood-vessels,  lymphatics  and  nerves.  It 
forms  the  submucous  coat.  This  in  turn  is  clad  with  epithelium, 
constituting  the  continuous  mucous  lining  of  the  entire  digestive  tract. 
Externally,  the  longitudinal  layer  of  smooth  muscle  tissue  is  enveloped 
by  a  thin  serous  layer,  the  peritoneum.  The  mechanical  processes 
associated  with  digestion,  are  mastication,  deglutition,  and  the  churn- 
ing movements  of  the  stomach,  small  intestine  and  large  intestine. 

Mastication. — The  articulation  between  the  mandible  and  max- 
illary bone  is  classified  as  a  double  condyloid  joint.  Owing  to  the 
looseness  and  strength  of  its  capsular  ligament,  the  articular  surfaces 
of  these  bones  may  be  moved  freely  upon  one  another,  allowing  the 
mandible  to  execute  three  types  of  movements  which  may  be  classi- 
fied as  (a)  depression  and  elevation,  (6)  projection  and  retraction,  and 
(c)  deviation  from  side  to  side.  Its  raising  is  effected  by  the  combined 
contraction  of  the  temporal,  masseter,  and  internal  pterygoid  muscles, 
and  its  depression  by  gravity  and  the  action  of  the  digastric  muscle 
in  conjunction  with  the  mylohyoid  and  geniohyoid.  At  this  time, 
the  hyoid  bone  is  fixed  by  the  contraction  of  the  omohyoid  and  sterno- 
hyoid muscles.  When  both  external  pterygoids  contract  simulta- 
neously, the  jaw  is  protruded.  The  opposite  movement  is  effected  by 
the  internal  pterygoids.  The  contraction  of  only  one  set  of  these 
antagonistic  muscles  gives  rise  to  a  deviation  of  the  jaw  toward  one 
side  or  the  other. 

The  grinding  motions  of  mastication  consist  chiefly  in  a  lowering 
and  raising  and  a  lateral  deviation  of  the  jaw,  the  food  being  kept 
between  the  molar  teeth  by  the  action  of  the  tongue,  the  orbicularis 
oris  and  the  buccinators.  The  action  of  these  parts  is  controlled  by  a 
reflex  center  which  is  situated  in  the  medulla  oblongata  and  includes 
the  nuclei  of  the  motor  nerves  innervating  the  aforesaid  muscles, 
namely,  those  of  the  trigeminal,  facial  and  hypoglossal  nerves.  On 
the  afferent  side,  this  center  is  connected  with  different  receptors,  and 
particularly  with  the  spindles  of  the  muscles  concerned  in  this  act. 
By  this  means,  the  force  and  character  of  the  movements  of  the  jaw  are 
reflexly  regulated.  The  closure  of  the  lips  and  depression  of  the  tongue 
and  jaw  during  inspiration  may  give  rise  to  a  negative  pressure  in  the 
oral  cavity,  approximating  25  to  50  cm.  H2O. 

The  importance  of  mastication  differs  in  different  animals.  In 
the  carnivora,  the  food  is  rapidly  projected  through  the  mouth  and  is 


THE    MECHANICS   OF   DIGESTION  1001 

swallowed  in  rather  lar}i;e  masses,  whereas  in  the  herbivora,  and  especially 
in  the  ruminating  mammals,  it  is  slowly  reduced  into  the  smallest 
possible  fragments.  Th(>  omnivora,  such  as  man,  occupy  an  interme- 
diate position  in  this  regard.  These  ditlerences  are  associated  with 
definite  peculiarities  in  the  shape  and  structure  of  the  parts  concerned 
in  mastication.  Thus,  we  find  tliat  the  teeth  of  the  carnivora  are 
well  adapted  to  catch  the  food,  while  those  of  the  ruminants  present  all 
the  characteristics  of  grinders.  In  man,  the  incisors  are  to  hold  and 
to  divide  the  footl,  whereas  the  canines  divide  it,  and  the  bicuspids 
and  molars  macerate  it.  The  development  of  these  parts  proceeds 
in  the  same  manner  as  that  of  the  hairs.  A  continuous  thickening  of 
the  epithelium  takes  place  along  the  gums  which  grows  into  the  corium 
of  the  mucosa  and  forms  the  dental  germ  or  dental  lamina.  Further 
thickenings  and  growths  give  rise  to  the  special  dental  germ  from  which 
the  milk  teeth  are  developed.  Each  germ  contains  a  vascular  papilla 
and  is  eventually  separated  from  the  general  mucous  membrane  by  a 
vascular  septum,  which  is  known  as  the  dental  sac.  The  papilla  is 
finally  transformed  into  the  dentine  and  pulp  of  the  growing  tooth, 
while  its  enamel  is  deposited  upon  this  core  by  the  epithelial  cells  of  the 
dental  germ.  Later  on,  as  the  tooth  grows  outward,  its  root  is  formed 
which  is  then  covered  with  cement. 

In  man,  the  teeth  appear  in  two  sets,  a  temporary  one  and  a  permanent  one. 
The  first  consists  of  the  so-called  milk  teeth.  They  are  twenty  in  number  and  appear 
between  the  5th  and  30th  month.  Their  time  of  appearance,  however,  varies 
considerably,  being  subject  to  family  characteristics,  and  the  condition  of  the  child. 
The  first  to  appear  are  the  two  central  incisors  below  (5th  to  9th  month),  next  the 
four  upper  central  teeth  (Sth  to  12th  month);  then  the  other  two  lower  central 
teeth  and  the  four  front  double  teeth  (12th  to  18th  month).  Thefour  incisors  follow 
next  (18th  to  24th  month),  the  upper  being  known  as  the  "eye  teeth"  and  the 
lower  as  the  "stomach  teeth."  The  four  back  double  teeth  which  complete  the 
first  set,  break  through  between  the  24th  and  30th  month.  Every  one  of  the 
milk  teeth  is  replaced  in  the  course  of  time  by  a  permanent  tooth.  This  change 
begins  at  about  the  7th  year  and  proceeds  in  about  the  same  sequence  as  the 
formation  of  the  temporary  set.  In  addition,  each  maxilla  acquires  six  new  teeth, 
three  on  each  side.  These  are  the  permanent  molars.  The  last  of  these,  or  wis- 
dom teeth,  appear  about  the  20th  year,  but  have  been  known  to  be  delaj^ed  until 
the  30th  year  and  later.  The  permanent  set,  therefore,  consists  of  thirty-two 
teeth. 

Deglutition. — In  brief,  the  process  of  mastication  consists  in  a 
mechanical  reduction  and  anointment  of  the  food  which  eventually 
leads  to  the  formation  of  the  bolus.  This  rounded  pulpy  mass  of  food 
is  then  projected  into  the  stomach  by  the  process  of  deglutition  or 
swallowing.  In  general,  it  may  be  said  that  the  onward  movement  of 
the  food  through  the  alimentary  canal  is  effected  b}'-  peristaltic  motion, 
but  the  gross  character  of  this  muscular  activity  differs  somcM'hat  in 
the  different  segments  of  this  channel.  The  act  of  deglutition  is 
divided  into  three  stages.  The  first  is  oral  in  its  character  and  termi- 
nates with  the  passage  of  the  bolus  through  the  pillars  of  the  fauces. 
The  second  concerns  the  constituents  of  the  pharynx  and  ends  with 


1002  DIGESTION 

the  entrance  of  the  food  into  the  upper  extremity  of  the  esophagus. 
The  third  is  restricted  to  the  esophagus  and  terminates  with  the 
arrival  of  the  food  in  the  cardiac  end  of  the  stomach.  It  is  also  to  be 
noted  that  the  first  is  effected  by  striated  muscle,  and  constitutes,  there- 
fore, a  voluntary  act,  whereas  the  last  two  are  due  almost  wholly  to 
the  contraction  of  smooth  muscle  tissue  and  are,  therefore,  involuntary 
or  reflex  in  their  nature.  In  spite  of  these  functional  differences,  how- 
ever, deglutition  is  a  continuous  act  and  no  pauses  occur  between  its 
successive  phases.  Further,  the  initiation  of  the  first  invariably  means 
the  completion  of  the  third,  although  some  persons  may  acquire  a 
limited  volitional  control  over  the  second. 

Immediately  before  the  beginning  of  the  first  stage,  the  process  of 
mastication  is  suspended.  Respiration  is  arrested  after  a  slight  con- 
traction of  the  diaphragm,  constituting  the  so-called  "respiration  of 
swallowing."  The  lips  are  closed  and  the  maxillce  closely  approxi- 
mated. The  tip  of  the  tongue  is  then  elevated  and  pressed  against  the 
the  inner  aspect  of  the  upper  gum.  The  muscles  effecting  this  move- 
ment are  the  inner  longitudinal  strands  of  the  tongue  which  are  con- 
trolled by  the  hypoglossal  nerve.  This  elevation  then  progressively 
involves  the  entire  tongue  from  before  backward,  forcing  the  bolus  in  the 
same  direction  through  the  fauces.  This  movement  brings  into  play  the 
muse,  mylohyoideus  (nerv.  trigeminus)  which  raises  the  hyoid  bone, 
as  well  as  the  muse,  styloglossus,  muse,  palatoglossus  and,  in  an  in- 
direct manner,  also  the  muse,  stylohyoid  (nerv.  facialis).  The  latter 
elevate  the  back  of  the  tongue,  so  that  its  inherent  muscle  strands  may 
progressively  obstruct  the  posterior  extent  of  the  oral  cavity. 

As  soon  as  the  bolus  has  been  forced  through  the  fauces,  it  is 
brought  under  the  control  of  the  three  sphincters  of  the  pharynx  which 
direct  it  into  the  upper  extremity  of  the  esophagus.  This  process 
necessitates  a  temporary  obstruction  of  the  nasal  and  laryngeal 
cavities.  The  closure  of  the  first  is  brought  about  by  the  simultaneous 
contraction  of  the  levator  palati  and  palato-pharyngeus  muscles,  the 
uvula  being  at  this  time  forced  in  contact  with  the  posterior  pillars,  and 
the  latter  in  turn  with  the  upper  posterior  wall  of  the  pharynx.  The 
closure  of  the  epiglottidean  orifice  necessitates  the  elevation  of  the 
hyoid  bone  and  an  upward  and  forward  movement  of  the  larynx.  The 
former  is  brought  about  by  the  contraction  of  the  geniohyoid,  anterior 
belly  of  the  digastric  and  mylohyoid,  and  the  latter,  by  the  contraction 
of  the  thyrohyoid.  At  this  time,  the  back  of  the  tongue  is  pulled 
backward  by  the  contraction  of  the  styloglossus,  thereby  forcing  the 
epiglottis  downward  across  the  laryngeal  orifice.  A  still  firmer 
closure  of  this  passage  is  effected  by  the  contraction  of  the  reflector 
epiglottis  and  aryepiglotticus,  as  well  as  by  the  constriction  of  the 
glottis  itself.  Stuart  and  McCormick,^  however,  have  shown  that  the 
removal  of  the  epiglottis  does  not  seriously  interfere  with  the  act. of 

^  Jour,  of  Anat.  and  Physiol.,  1892;  also:  Kanthak  and  Anderson,  Jour,  of 
Physiol.,  xiv,  1893,  154. 


THE    MECHANICS    OF    DIGESTION  1003 

swallowing,  because  the  backward  inoveineut  of  the  tongue  and  upward 
deviation  of  the  larynx  usually  suffice  to  prevent  an  ingress  of  food 
into  the  respiratory  passage. 

At  about  the  level  of  the  closed  epiglottidean  orifice,  the  bolus  is 
brought  under  the  influence  of  the  middle  and  inferior  constrictors  of 
the  pharynx,  the  successive  contractions  of  which  force  it  into  the 
upper  segment  of  the  esophagus.  It  has  been  shown  by  Kronecker 
and  Falk^  that  fluids  pass  more  rapidly  and  usually  do  not  require  a 
concerted  action  of  the  parts  just  enumerated;  in  fact,  the  movements 
of  the  back  of  the  tongue  generally  suffice  to  direct  them  through  the 
relaxed  upper  segment  of  the  esophagus  into  its  lower  portion.  It  is 
for  this  reason  that  some  persons,  under  abolition  of  the  pharyngeal 
reflexes,  are  able  to  pour  considerable  quantities  of  water  almost- 
direct  1}^  into  the  cardia.  This  also  explains  the  fact  that  the  erosions 
produced  by  the  hasty  intake  of  corrosive  fluids,  are  usually  most 
severe  in  the  lower  esophagus. 

It  has  been  shown  by  Cannon  and  Moser^  that  the  progression  of 
semi-sohd  food  through  the  esophagus  takes  place  much  more  leisurely, 
and  is  effected  by  peristaltic  waves  which  proceed  from  above  down- 
ward. It  will  be  remembered  that  the  smooth  musculature  of  this 
membranous  tube  is  arranged  in  two  layers,  namely,  as  an  inner 
circular  and  an  outer  longitudinal  coat.  A  peristaltic  wave,  however, 
does  not  consist  solely  of  a  contraction  of  the  circular  fibers,  but  pre- 
sents itself  in  all  instances  as  a  progressive  wave  of  constriction  which 
is  anteceded  by  a  wave  of  relaxation,  the  bolus  being  driven  ahead  of 
the  contracting  band  of  muscle  tissue  in  the  direction  of  least  resistance. 
But  since  the  upper  and  even  the  middle  segments  of  the  esophagus 
contain  a  few  strands  of  striated  muscle  tissue,  it  cannot  surprise  us  to 
find  that  the  progress  of  the  bolus  is  more  rapid  above  than  in  the  vi- 
cinity of  the  cardia.  According  to  Schreiber,^  the  entire  act  of  peristal- 
sis for  semi-sohd  food  consumes  about  6  seconds,  about  one-half  of 
this  period  being  occupied  by  the  passage  of  the  bolus  through  the  lower 
segment  of  the  esophagus. 

A  ver>^  appreciable  retardation  also  results  at  the  cardiac  sphincter 
which  guards  the  gastric  orifice  of  the  esophagus.  This  circular 
ring  of  smooth  muscle  tissue  relaxes  only  under  the  gradually  increas- 
ing force  of  the  newly  arrived  bolus.  Obviously,  this  mechanism  pre- 
vents the  sudden  ingress  of  the  food  into  the  stomach  as  well  as  its 
immediate  projection  into  the  fundic  portion  of  this  organ. ^  On 
listening  over  the  region  of  the  cardia  when  fluid  is  taken,  two  sounds 
are   heard,  the  first  of  which  is   produced  by  its  sudden  projection 

1  Archiv  ftir  Anat.  und  Physiol.,  1880,  296. 

-  Am.  Jour,  of  Phj'siol.,  i,  1899,  435,  and  Evkmann,  Pfliiger's  Archiv,  xcix, 
1903,  513. 

3  Archiv  ftir  exp.  Path,  und  Pharm.,  xlvi,  1901,  414. 

^  Beaumont's  observations  upon  Alexis  St.  Martin,  also  Hertz,  Guj^'s  Hosp. 
Rep.,  London,  1907. 


1004  DIGESTION 

through  the  esophagus,  and  the  second,  by  its  gurghng  through  the 
cardiac  orifice. 

Nervous  Control  of  Deglutition. — The  act  of  swallowing  involves 
the  voluntary  mechanisms  of  the  mouth  and  pharynx,  and  the  invol- 
untary mechanism  of  the  esophagus.  Consequently,  deglutition  may 
be  treated  as  a  reflex  act  which  is  evoked  by  the  projection  of  the  bolus 
against  the  mucosa  of  the  fauces  and  pharynx,  regions  which  are  in- 
nervated, on  the  one  hand,  by  the  trigeminus  and,  on  the  other,  by  the 
glossopharyngeus.  Besides  these  normal  "pace-makers,"  this  passage 
also  includes  several  other  areas  which  upon  mechanical  stimulation 
give  rise  to  deglutition.  ^  The  afferent  channels  involved  in  this  reflex 
lie  in  the  second  division  of  the  trigeminus,  the  glossopharyngeus 
and  the  pharyngeal  branches  of  the  superior  laryngeus,  whereas  the 
center  occupies  a  place  in  the  upper  part  of  the  medulla  oblongata. 
The  motor  fibers  are  contained  in  the  hypoglossal,  facial,  trigeminus, 
and  vagus  nerves. 

This  enumeration  shows  very  clearly  that  the  parts  involved  in 
deglutition,  are  arranged  segmentally,  but  the  sensory  and  motor 
nerves  controlling  them,  are  coordinated  in  so  precise  a  manner  that 
no  interruption  can  possibly  result  in  the  orderly  progression  of  the 
wave  of  contraction.  Thus,  Meltzer^  has  shown  that  the  peristaltic 
wave  does  not  require  an  integrity  of  the  muscular  tube  so  long  as  the 
nervous  mechanisms  have  not  been  interfered  with,  while  Mosso' 
has  proved  that  a  ligature  applied  to  the  esophagus,  does  not  block 
this  wave,  provided  the  reflex  circuits  have  not  been  broken.  An 
even  more  striking  proof  of  the  successive  involvement  of  the  different 
segments  of  this  membranous  tube  has  been  furnished  by  Mikulicz. 
It  concerns  a  man  whose  esophagus  had  been  resected  in  part  for  the 
removal  of  a  carcinomatous  growth.  The  lower  segment  of  this  tube 
was  made  to  open  through  a  wound  in  the  neck,  the  purpose  of  this 
arrangement  being  to  allow  the  food  to  reach  the  stomach  in  the  normal 
way.  It  was  found,  however,  that  its  introduction  through  this  open- 
ing did  not  incite  peristalsis,  whereas  it  was  moved  onward  immedi- 
ately if  the  act  of  swallowing  was  instigated  in  the  normal  way  by 
the  corresponding  movements  of  the  mouth  parts. 

An  interval  of  at  least  1.0  second  must  intervene  between  the  suc- 
cessive acts  of  swallowing,  otherwise  certain  inhibitor  influences  will 
arise  which  effectively  block  the  succeeding  peristalsis.  This 
inhibition  is  said  to  be  under  the  control  of  the  glossopharyngeus, 
because  it  is  a  well-known  fact  that  the  normal  pace-maker  of  deglu- 
tition is  represented  by  the  nucleus  of  this  nerve.  Evidently,  this 
refraction  allows  each  act  of  deglutition  to  be  completed  before  the 
beginning  of  the  next,  although  it  may  happen  at  times  that  new  food 
reaches  the  cardiac  sphincter  before  the  material  swallowed  previ- 

1  Kahn,   Archiv  fiir  Physiol.,  1903,  Suppl.,  386. 

2  Brit.  Med.  Jour.,  1906. 

^  Moleschott's  Untersuchungen,  1876. 


THE    MECHANICS    OF    DIGESTION 


1005 


ously,  has  had  sufficient  time  to  escaiM;  into  tlu;  stomach.  This  inter- 
fereneo  invariably  gives  rise  to  painful  sensations  and  regurgitation 
of  the  food. 

It  should  also  be  noted  that  the  afferent  impulses  which  determine 
the  activity  of  the  center  of  deglutition,  cause  a  stoppage  of  the  respir- 
atory movements.  This  is  important,  because  an  inspiratory  motion 
occurring  during  deglutition,  might  draw  the  food  into  the  respiratory 
passage,  when^as  an  expiration  occurring  at  this  time,  might  force  it 
into  the  nasal  cavity.  The  fact  that  this  inliibition  of  respiration  is 
effected  with  the  help  of  the  glossopharyngeal  nerve,  may  be  proved 
by  stimulating  the  fauces  and  neighboring  regions  of  the  pharynx, 
either  mechanically  or  electrically.  We  have  previously  seen  that 
an  analagous  reaction  may  be  produced  by  the  excitation  of  the 
mucous  membrane  Uning  the 
nasal  (trigeminus)  and  laryngeal 
cavities  (sup.  laryngeal  nerve). 
Thus,  it  cannot  surprise  us  to  find 
that  the  introduction  of  a 
stomach-tube  gives  rise  to  an 
•almost  immediate  inhibition  of 
respiration  which  persists  even 
after  a  severe  cyanosis  has  been 
established.  Repeated  attempts 
at  swallowing,  however,  will  tem- 
porarily remove  the  inhibition 
and  allow  the  subject  to  replenish 
the  oxygen  content  of  his  blood. 
A  close  reflex  relationship  also 
exists  between  the  center  of  deg- 
lutition and  the  cardiac  center, 
as  is  evinced  by  the  fact  that  the 
act  of  swallowing  increases  the 
rate  of  the  heart. 


Fro.    511. — Diagrammatic  Repke.sextation' 
OF  THE  Stomach. 

C,  Cardiac  end;  F,  fundus;  P,  pylorus; 
D,  duodenum;  CS,  cardiac  sphincter;  SA, 
sphincter  antri  pylori;  PS,  pyloric  sphinc- 
ter; V,  valvulae  conniventes. 


B.  THE  MOVEMENTS  OF  THE  STOMACH 

The  Movements  of  the  Fundus  and  Pylorus. — The  muscular 
coat  of  the  stomach  consists  essentially  of  an  outer  longitudinal  and  an 
inner  circular  layer.  To  these  are  added  in  certain  areas  of  this  organ 
an  inner  layer  of  obhquely  placed  muscle  strands  which  serve  to 
strengthen  its  wall  along  its  anterior  and  posterior  surfaces  below  the 
cardia.  The  layer  of  circular  strands  is  the  heaviest  of  all  and  is  of  great- 
est functional  importance.  At  the  pyloric  and  esophageal  poles  of  the 
stomach  it  suddenly  increases  in  thickness,  forming  here  the  so-called 
pyloric  and  cardiac  sphincters.  A  third  band  of  circular  fibers  invests 
the  stomach  at  the  junction  between  its  fundic  and  pyloric  portions, 
i.e.,  about  7  to  10  cm.  above  the  pylorus.     It  is  known  as  the  sphincter 


1006  DIGESTION 

antri  pylori  and  corresponds  to  the  point  of  origin  of  the  peristaltic 
movements  of  the  pyloric  end  of  this  organ.  It  is  also  of  interest  to 
note  that  this  muscular  band  is  more  highly  constricted  in  some 
persons  than  in  others,  giving  rise-  to  the  so-called  hour-glass  stomach. 
While  this  condition  may  be  inherited,  it  is  more  commonly  caused  by 
excitations  of  the  gastric  mucosa,  such  as  may  arise  in  consequence  of 
erosions  and  ulcers.  The  onter  longitudinal  layer  continues  at  the 
cardia  with  the  longitudinal  fibers  of  the  esophagus,  and  is  heaviest 
along  the  greater  and  lesser  curvatures  of  the  stomach.  At  the  pylo- 
rus it  passes  over  into  the  longitudinal  layer  of  muscle  tissue  of  the 
duodenum. 

Anatomically,  therefore,  the  stomach  may  be  divided  into  two 
compartments,  namely,  into  its  pyloric  portion  or  antrum  pylori, 
comprising  about  one-fifth  of  the  entire  organ,  and  its  much  larger 
fundic  portion  and  cardiac  recess.  This  division  also  possesses  a 
correct  physiological  basis,  because  the  antrum  pylori  is  infinitely 
more  active  than  the  fundus,  so  much  so,  in  fact,  that  the  latter  is 
commonly  regarded  as  the  reservoir  of  the  former.  A  more  thorough 
study  of  these  movements  may  be  made  with  the  help  of  the  following 
methods : 

(a)  Observation  of  the  manner  in  which  the  gastric  contents  are  discharged 
through  a  duodenal  fistula.^ 

(b)  Introduction  of  a  small  rubber  bag  into  the  cavity  of  the  stomach  which  is 
connected  with  a  recording  tambour. ^ 

(c)  Inspection  of  the  interior  of  the  stomach  through  a  fistulous  opening 
(Beaumont). 

{d)  Observation  of  the  stomach  through  a  wound  in  the  abdominal  wall,  a 
piece  of  mica  being  inserted  in  the  opening  to  protect  the  stomach  against  external 
stimuli. 

(e)  Observation  of  the  excised  stomach  under  proper  conditions  of  moisture 
and  temperature.  3 

(/)  Observation  of  the  stomach  by  means  of  the  Rontgen-rays  after  the  inges- 
tion of  food  containing  subnitrate  of  bismuth.'' 

The  empty  stomach  is  small  in  size,  but  its  walls  cannot  collapse, 
because  a  thin  layer  of  frothy  material  remains  interposed  between 
them.  This  froth  consists  of  mucus  and  a  few  cubic  centimeters  of 
gastric  juice.  At  this  time,  the  intragastric  pressure  is  zero.  The 
entrance  of  food  then  separates  its  walls  more  widely  but  chiefly  those 
of  the  cardia,  because  the  newly  swallowed  material  collects  at  first  di- 
rectly below  the  esophageal  orifice.  Here  it  may  remain  in  a  rela- 
tively undisturbed  condition  for  nearly  an  hour,  salivary  digestion 
going  on  unhindredly  during  the  interim.  This  fact  is  well  illustrated 
by  the  experiments  of  Griitzner,^  who  fed  rats  successively  with  semi- 

1  Hirsch,  Zentralbl.  klin.  Med.,  1892. 

2  Ducceshi,  Arch.  itil.  de  Biol.,  xxvii,  1897,  61. 

^  Hofmeister  and  Stutz,  Archiv  fiir  Exp.  Path,  und  Pharm.,  xx,  1885,  1. 
*  Roux  and  Balthasard,  Compt.  rend.,  1897,  and  Cannon,  Am.  Jour,  of  Physiol. 
i,  1898,  359,  and  xii,  1904,  387. 

5  Pfluger's  Archiv,  cvi,  1905,  463. 


THE    MECHANICS    OF    DIGESTION  1007 

solid  food  of  different  color  and  found  it  later  on  arranged  in  concentric 
strata  in  the  vicinity  of  the  esophageal  orifice.  The  material  ingested 
first  was  pushed  downward  and  outward  toward  the  gastric  wall, 
while  that  eaten  last,  occupied  the  central  extent  of  this  space.  This 
slow  whirling  about  of  the  food  serves  to  bring  its  different  portions 
into  more  intimate  contact  with  the  walls  of  the  fundus  and,  therefore, 
also  with  the  gastric  juice.  Eventually,  whcm  even  its  innermost  mass 
has  been  conii)letely  acidified,  the  action  of  theptyalin  ceases,  wiiile  that 
of  the  pepsin  begins.  As  far  as  the  mechanical  function  of  the  fundus 
is  concerned,  it  may  therefore  be  said  that  this  gastric  segment  acts 
merely  as  a  reservoir  for  the  digestive  tract.  Considerable  amounts  of 
food  may  be  stored  in  it  which  are  then 
fed,  hopper-like,  to  the  pyloric  mill  for 
mechanical  and  chemical  reduction. 
This  function  does  not  require  an  un- 
usual muscular  activity,  because  gravity 
and  the  pressure  exerted  by  the  food  as 
it  slowly  oozes  through  the  relaxed  car 
diac  sphincter,  no  doubt  suffice  to  force 
it  toward  the  sphincter  antri  pylori. 
Later  on  in  the  course  of  gastric  diges- 
tion, its  walls    contract  more  forcibly  in  Fig.  6I2. — Section  of  Frozen 

1        ,         , A      -i  ]  J      J-  Stomach  of  Rat  During  Digestion 

order  to  empty  its  more  dependent  por-     ^„   g^^^   ^^^    Stratification   of 

tions,    a   regurgitation   of  the  food  being     Food  Given  at  Different  Times. 

prevented  at  this  time  by  the  closure  of    (Grutzner.) 

the  cardiac  sphincter.     But  the  pressure 

present  in  this  compartment  at  the  height  of  digestion,  rarely  exceeds 

6  to  8  cm.  of  water.  ^ 

The  mechanical  conditions  existing  in  the  pyloric  end  of  the 
stomach,  differ  widely  from  those  just  described.  Food  having  been 
received,  a  band-like  constriction  appears  at  the  sphincter  antri 
pylori  which  gradually  increases  in  depth  until  the  fundus  has  been 
completely  shut  off  from  the  pylorus.  This  circular  constriction  then 
moves  slowly  toward  the  pyloric  sphincter,  where  it  arrives  about  20 
seconds  later.  Some  time  before  it  disappears  another  one  develops 
and  progresses  in  the  same  direction.  In  this  way,  a  number  of  peri- 
staltic waves  are  produced  which  force  the  food  toward  the  pylorus, 
whence  it  recoils  along  the  wall  toward  its  starting  point.  As  many 
as  three  of  these  waves  may  be  observed  at  one  time.  Thus,  one  may 
just  be  disappearing  at  the  pylorus,  while  another  is  still  at  some  dis- 
tance from  it,  and  a  third  is  just  forming  at  the  antrum.  Although  the 
intensity  and  frequency  of  these  waves  vary  with  the  time  of  gastric 
digestion,  they  usually  recur  at  intervals  of  about  10  seconds  (cat) 
and  invariably  proceed  from  the  fundus  toward  the  pylorus.  Anti- 
peristaltic movements  occur  only  under  pathological  conditions. 

1  Kelling,  Zeitschr.  fur  Biol.,  xliv,  1903,  161;  and  Schlippe,  Deutsch.  Arch, 
klin.  Med.,  Ixxvii,  1903,  450. 


1008 


DIGESTION 


In  man  these  movements  may  be  studied  with  the  help  of  the  Ront- 
gen-rays,  the  person  to  be  examined  having  previously  ingested  a  mix- 
ture of  koumiss  and   subnitrate  of  bismuth.     Most  commonly,  these 


Fig.  513.— Roentgen-  CixEM.A.TOGR.\iis  of  the  Humax  Stomach.      (Kiistle,  Rieder,  and 

Rosenthal.) 

examinations  are  made  in  the  standing  position,  so  as  to  be  able  to 
note  the  lower  boundary  of  the  stomach,  and  to  be  able  to  determine 


THE    MECHANICS    OF    DIGESTION  1009 

whotlier  this  orgiin  possesses  a  muscular  powc^r  sufficient  to  force  its 
contents  through  the  pyloric  orifice.  Ol)viously,  the  latter  is  situated 
at  this  tiuK^  somewhat  above  tlie  level  of  the  general  cavity  of  the  py- 
lorus. Moreover,  when  standing  erect,  tlu^  stomach  assumes  more 
nearly  the  shape  of  a  suspended  stocking  and  allows  the  gases  to  escape 
very  freely,  whereas,  when  lying  down,  the  (esophageal  orifice  assumes 
a  position  somewhat  below  the  level  of  th(^  general  gastric  cavity  and 
entraps  any  gases  that  may  have  Ix'cn  foi-med. 

The  Evacuation  of  the  Gastric  Contents. — The  purpose  of  the  peri- 
staltic movements  of  the  stomach  is  to  mix  the  food  with  the  gastric 
juice,  and  to  reduce  it  eventually  into  a  liquid  which  is  known  as 
the  chyme.  In  this  form,  the  gastric  contents  are  then  ejected  through 
the  relaxed  pyloric  orifice  into  the  duodenum.  The  muscular  activity 
which  is  required  to  accomplish  this  end  is  somewhat  different  from 
that  previously  noted  in  the  course  of  the  formation  of  the  chyme. 
It  consists  essentially  in  a  contraction  of  the  horizontal  and  oblique 
layers  of  muscle  tissue  which  employ  the  cardia  as  a  fixed  point  and 
raise  the  fundus  above  the  general  level  of  the  pylorus.  Meanwhile, 
the  pylorus  continues  its  peristaltic  activity,  and  forces  its  contents  to- 
ward the  pyloric  orifice.  Naturally,  the  chyme  cannot  escape  as  long 
as  this  sphincter  remains  closed  and  must  in  this  event  be  whirled 
back  along  the  sides  of  the  gastric  wall. 

Two  reasons  may  be  assigned  for  the  continued  closure  of  this 
sphincter,  namely:  (a)  the  gastric  contents  still  contain  solid  masses 
which  exert  a  mechanical  influence  upon  the  mucosa  of  this  region, 
and  (6)  the  gastric  contents  have  not  as  yet  been  sufficiently  acidified.^ 
Contrariwise,  if  the  gastric  contents  have  been  thoroughly  liquefied 
and  acidified,  these  mechanical  and  chemical  stimulations  cease  and 
allow  the  sphincter  to  relax.  The  chyme  is  then  ejected  into  the  duo- 
denum, being  here  thrown  against  the  upper  surfaces  of  the  valvulsB 
conniventes  which  extend  as  transverse  flaps  partially'  across  the  lumen 
of  this  passage.  The  presence  of  acid  in  the  duodenum  then  effects 
the  closure  of  the  pyloric  orifice.  Thus,  the  ejection  of  chyme  is  im- 
mediately followed  by  a  constriction  of  the  sphincter  until  the  acid 
liquid  in  the  duodenum  has  again  been  neutralized.  The  ejection  of 
chyme  is  then  repeated.  Consequently,  it  may  be  concluded  that  the 
opening  and  closing  of  the  pyloric  sphincter  is  dependent  upon  the 
physical  copditiori  of  the  gastric  juice  as  well  as  upon  the  relative  de- 
grees of  acidity  in  the  cavities  of  the  stomach  and  duodenum.  Conse- 
quently, the  evacuation  of  the  stomach  is  not  a  continuous  act,  but 
takes  place  at  intervals  until  its  cavity  has  been  completely  emptied. 
The  nervous  mechanism  concerned  in  this  reflex  act,  lies  in  the  domain 
of  the  plexus  gastro-duodenalis. 

The  Time  of  Evacuation  of  the  Gastric  Contents. — The  preceding 
discussion  must  show  immediately  that  the  time  of  evacuation  of  the 
gastric  contents  is  subject  to  considerable  variations  which  depend 

'  Hirsch,  Zentralbl.  flir  innere  Med.,  1901. 

G4 


1010 


DIGESTION 


not  only  upon  the  force  and  frequency  of  the  peristalsis,  but  also  upon 
the  character  of  the  food  ingested.  Thus,  Cannon^  has  shown  that  the 
carbohydrates  begin  to  leave  the  stomach  soon  after  their  ingestion 
and  require  only  about  one-half  the  time  necessary  for  the  complete 
digestion  of  the  proteins.  Fats,  when  ingested  alone,  remain  in  the 
stomach  for  a  long  time.  Quite  similarly,  the  simultaneous  intake  of 
different  foodstuffs  markedly  interferes  with  the  evacuation  of  those 
whigh  otherwise  escape  very  rapidly.  Accordingly,  if  protein  is  fed 
before  the  carbohydrates,  the  latter  are  retarded,  whereas  fat  tends  to 
hinder  the  progress  of  both.  In  general,  however,  it  may  be  said  that 
a  moderate  meal,  consisting  of  all  foodstuffs,  should  be  out  of  the 
stomach  after  four  hours,  and  its  ejection  should  begin  within  an  hour 
after  its  ingestion.  The  first  portion  of  this  chyme,  therefore,  may 
have   arrived   at  the  iliocecal  valve  before  its  last  portion  has  trav- 


Fig.  514. — Shadows  of  the  Human  Stomach  Obtained  with  the  Aid  of  the  Rontgen 
Eays  15  Minutes,  1  Hour,  and  4  Hours  after  Ingestion  of  the  Bismuth  Meal. 

ersed  the  pyloric  orifice.  These  facts  imply  that  a  stomach  which 
still  contains  material  at  the  end  of  five  hours,  either  lacks  tonicity  or 
is  unable  to  discharge  on  account  of  some  obstruction,  possibly  a 
pyloric  stricture.  Water  and  isotonic  salt  solutions  are  passed  into  the 
duodenum  very  rapidly.  Hypertonic  solutions  and  other  drinks, 
such  as  coffee  and  tea,  require  a  somewhat  longer  time.^  As  far  as 
the  intake  of  moderately  large  quantities  of  water  during  meals  is 
concerned  it  may  be  stated  in  general  that  it  serves  the  purpose  of 
hastening  the  formation  of  chyme,  although  it  may  also  tend  to  dilute 
the  gastric  juice  to  such  an  extent  that  its  digestive  power  is  unduly 
diminished.  In  view  of  the  results  of  Carlson,  however,  showing  that 
very  abundant  amounts  of  hydrochloric  acid  and  pepsin  are  held  in 
reserve,  the  latter  possibility  is  rather  remote,  and  should  be  taken 
into  consideration  only  when  a  hypochlorhydria  is  present. 

Gastro-enterostomy. — The  operation  of  gastro-enterostomy  con- 
sists in  uniting  the  lower  duodenum  directly  with  the  stomach  distally 
to  its  sphincter  antri  pylori.     Physiologically,  it  is  of  importance  to 

1  Am.  Jour,  of  Physiol.,  xii,  1904,  387. 

'■  Arch,  fiir  Exp.  Path,  und  Pharm.,  Ui,  1905,  370,  and  MuUer,  Zeitschr.  fiir 
diat.  und  phys.  Ther.,  viii,  1905. 


THE    MECHANICS    OF    DIGESTION  1011 

romomlxM*  that  unless  the  fistulous  couununication  is  very  large,  the 
food  will  nevertheless  pass  through  the  pylorus,  ('onsequently,  the 
pyloric  obstruction  must  b(^  rather  completer  before  the  fistula  can 
serve  its  purpose.  Secondly,  it  has  been  o])served  in  animals  that 
some  of  the  material  which  has  left  the  stomach  by  way  of  the  pylorus 
again  enters  this  organ  through  \\\v  fistulous  communication.  Thirdly, 
the  outpouring  of  the  acid  gastric  juice  into  intestinal  segments  which 
are  normally  not  directly  exposed  to  it,  may  lead  to  erosions  and  ulcera- 
tions of  the  mucosa,  and  especially  if  the  blood-  or  nerve-supply  have 
in  any  way  been  interfered  with  during  the  operation.  Consequently, 
such  a  communication  should  not  be  established  in  the  absence  of 
organic  disease  of  the  pylorus. 

Vomiting. — The  act  of  vomiting  is  a  complex  reflex  in  which 
different  muscles  take  part  and  which  is  usually  preceded  by  a  sensa- 
tion of  nausea,  a  reflex  secretion  of  saliva,  and  other  symptoms  of  a 
more  general  character.  In  the  suckling  it  consists  essentially  of  a 
contraction  of  the  musculature  of  the  stomach  and  a  relaxation  of  the 
esophagus  and  presents,  therefore,  the  simplest  possible  details.  In 
the  adult,  on  the  other  hand,  other  factors  are  brought  into  play, 
chief  among  which  is  the  abdominal  press.  The  latter  consists  in  a 
spasmodic  contraction  of  the  abdominal  muscles,  inclusive  of  the 
diaphragm,  following  a  short  inspiration  and  closure  of  the  glottis. 
It  is  apparent,  how^ever,  that  in  the  adult  the  stomach  plays  a  rather 
subordinate  part,  as  is  evinced  by  the  fact  that  the  retching  movements 
occurring  at  the  beginning  of  the  act  of  vomiting,  which  are  wholly 
of  gastric  origin,  are  altogether  too  weak  to  eject  the  gastric  contents. 
Moreover,  it  has  been  shown  by  Gianuzzi  that  this  act  cannot  be 
evoked  in  curarized  animals,  because  this  agent  paralyzes  the  muscles 
of  the  abdomen.  In  addition,  it  has  been  proved  by  Magendie  that 
vomiting  also  results  in  animals  whose  stomach  has  been  replaced 
by  a  bladder  filled  with  water. 

During  the  act  of  vomiting  the  peristalsis  is  abolished,  although 
intense  movements  of  this  kind  may  take  place  shortly  beforehand. 
Irregular  retching  motions  then  result  which,  however,  do  not  seem  to 
be  antiperistaltic  in  their  character.  The  essential  factor  concerned 
in  vomiting,  is  the  production  of  a  high  intragastric  pressure,  which, 
as  we  have  just  seen,  is  the  direct  result  of  the  contraction  of  the 
abdominal  muscles  and  smooth  musculature  of  the  stomach.  The 
pylorus  is  tightly  closed  at  this  time,  while  the  cardiac  sphincter  and 
esophagus  are  relaxed.^  An  eructation  of  gas  frequently  precedes 
this  act,  in  fact,  many  animals  such  as  the  dog  hasten  its  occurrence  by 
distending  the  stomach  with  freshly  swallowed  air.  Vomiting  also 
necessitates  a  forw^ard  movement  of  the  hyoid  bone  and  larynx, 
as  well  as  a  projection  of  the  mandible.  Both  measures  serve  to 
straighten  the  channel  of  ejection.  Although  the  nasal  cavity  is 
partly  protected  against  the  ingress  of  vomited  material  by  the  con- 

^  Openchowski,  Archiv  fiir  Physiol.,  1889,  552. 


1012  DIGESTION 

traction  of  the  upper  constrictor  and  the  approximation  of  the  pharyn- 
geal wall  and  pillars  of  the  fauces,  the  force  of  the  ejection  is  sometimes 
so  great  that  this  hindrance  is  overcome. 

The  act  of  vomiting  is  controlled  by  a  special  center  situated  in  the 
medulla  oblongata.  On  the  efferent  side,  it  is  connected  with  the 
different  muscles  mentioned  previously  and,  on  the  afferent  side,  with 
various  local  and  general  receptors.  Thus,  it  is  a  well-known  fact  that 
the  sight  and  smell  of  offensive  food  or  objects  may  serve  as  ade- 
quate exciting  causes,  and  that  it  may  also  be  evoked  by  the  mechanical 
stimulation  of  the  fauces  and  pharynx,  as  well  as  by  irritations  of  the 
gastric  and  intestinal  mucosa.  Even  extragastric  stimuli  in  the  form 
of  abdominal  tumors  and  the  gradually  enlarging  uterus  of  pregnancy 
may  instigate  it.  Apomorphin  produces  its  characteristic  effect  by 
a  direct  stimulation  of  the  vomiting  center. 

The  Innervation  of  the  Gastric  Musculature. — The  stomach  is 
wholly  under  the  control  of  the  autonomic  nervous  system,  the  distal- 
most  fibers  of  which  are  expanded  between  its  circular  and  longitudinal 
layers  of  muscle  tissue  into  the  plexuses  of  Meissner  and  Auerbach. 
This  organ,  therefore,  is  well  equipped  with  a  local  reflex  mechanism 
which  is  destined  to  regulate  its  various  motor  activities.  Thus,  it 
has  been  ascertained  that  the  excised  stomach,  if  kept  under  proper 
conditions  of  moisture  and  temperature,  may  be  made  to  contract 
upon  local  stimulation,  and  may  even  show  a  spontaneous  activity. 
Under  normal  conditions,  this  peripheral  sympathetic  mechanism 
is  connected  with  the  central  nervous  system  by  way  of  the  two  vagi 
and  splanchnic  nerves.  The  former  terminate  in  the  vicinity  of  the 
cardia  in  two  ramifications  which  are  known  as  the  ventral  and  dorsal 
gastric  plexuses.  From  here  fibers  pass  over  to  the  left  suprarenal 
plexus  of  the  splanchnic  system,  as  well  as  to  the  neighboring  region 
of  the  lesser  curvature.  At  the  present  time,  however,  no  evidence 
is  at  hand  to  show  that  these  plexuses  also  send  fibers  directly  to  the 
greater  curvature  or  to  the  region  of  the  pylorus.  The  latter  seem  to 
derive  their  innervation  from  the  celiac  ganglion  of  the  solar  plexus 
by  way  of  the  celiac  and  splenic  plexuses. 

It  can  no  longer  be  doubted  that  the  vagi  nerves  embrace  musculo- 
motor  nerves  for  this  organ.  This  is  proved  by  the  fact  that  their 
stimulation  above  the  diaphragm  evokes  well  marked  contractions 
which  involve  chiefly  its  pyloric  segment  and  possess  all  the  charac- 
teristics of  regular  peristaltic  waves.  While  it  is  commonly  stated 
that  the  splanchnic  nerves  exert  an  inhibitory  influence  upon  the 
movements  of  this  organ,  it  cannot  be  said  that  this  view  possesses  a 
satisfactory  experimental  basis.  Inasmuch  as  these  nerves  contain 
powerful  vasoconstrictors,  the  relaxing  effect  sometimes  observed 
upon  their  stimulation,  may  in  reality  be  caused  by  a  diminution  in 
the  gastric  blood-supply.^  Since  the  musculo-motor  function  of  the 
vagi  nerves  has  been  well  established,  it  may  be  said  that  their  nuclei, 
1  Burton-Opitz,  Pfliiger's  Archiv,  xxxv,  1910,  205. 


THE    MECHANICS    OK    DIGESTION  1  0  1 ;') 

in  conjunction  with  some  lulditional  frjinKlion  cells,  t'onn  ;i  ccntci-  wliich 
regulates  the  activity  of  the  intrafj;astric  reflex  mechanism.  This 
meihiUary  center  is  connected  willi  diiTereiit  afferent  chaiinels  through 
whicli  sensor}'  impulses  are  euahled  to  reach  it.  They  are  iiere  con- 
verted into  motor  impulses  and  relayed  to  the  intragastric  plexuses. 
Thus,  Wertheimer'  has  shown  that  the  stimulation  of  the  central  end 
of  the  sciatic  nerve  gives  rise  to  a  n^flex  inhibition  of  the  gastric  move- 
ments. Accellerat-ory  and  inhihiloi-y  effcn-ts  may  also  \)v.  pro(luc(;d 
by  psychic  influenc(>s,  such  as  delight,  anxiety,  anger  and  fright. 

C.  THE  MOVEMENTS  OF  THE  INTESTINES 

The  Movements  of  the  Small  Intestine. — Since  the  entrance  of  air 
into  the  abdominal  cavity,  the  evaporation  of  the  serous  fluid  and 
the  lowering  of  the  temperature  generally  induce  a  refractory  state 
in  this  organ,  various  precautions  must  be  taken  in  order  to  avoid 
this  motor  disturbance.  Thus,  it  has  been  advocated  to  insert  an  oval 
piece  of  glass  or  mica  in  the  incision  in  the  abdominal  wall,  or  to  open 
the  peritoneal  cavity  in  a  bath  of  warmed  saline  solution.  In  rabl)its 
it  is  possible  to  thin  the  abdominal  wall  in  such  a  degree  that  the  ab- 
dominal organs  may  be  inspected  without  actually  opening  this  cavity. 
These  methods  have  been  supplemented  at  an  early  date  by  graphic 
procedures,  consisting  in  fastening  a  soft  rubber  bulb  to  the  surface  of 
the  abdomen  or  in  inserting  it  directly  into  the  intestinal  canal.  Air 
transmission  being  employed  in  both  these  cases,  the  recording  tambour 
accurately  registers  the  displacements  of  the  air  from  the  bulb. 
Another  means  which  is  now  extensively  used,  is  the  fluoroscope  which 
allows  us  to  follow  the  food  in  its  course  through  the  aUmentary  canal 
by  virtue  of  the  fact  that  subnitrate  of  bismuth  when  mixed  with 
the  ingesta,  does  not  allow  the  Rontgen  rays  to  pass.  Lastly,  it  is 
possible  to  study  excised  segments  of  intestine  under  proper  conditions 
of  moisture  and  temperature;  They  may  then  be  connected  with 
recording  levers  and  pneumographs.  A  special  piece  of  apparatus  of 
this  kind  is  the  enterograph. 

The  arrangement  of  the  musculature  of  the  small  intestine  is 
simple;  an  outer,  relatively  thin  coat  of  horizontal  muscle  fibers  Hes 
in  relation  with  an  inner  circular  coat.  It  should  be  noted,  however, 
that  the  structure  of  its  different  segments  is  not  absolutely  uniform, 
but  shows  certain  variations  with  regard  to  the  thickness  of  the 
muscle  tissue.  Thus,  it  wdU  be  found  that  the  jejunum  is  large  in 
caliber  and  very  muscular,  while  the  ileum  is  narrow  and  possesses 
much  thinner  walls.  Similar  differences  are  encountered  in  the  dif- 
ferent segments  of  the  duodenum. 

The  movements  occurring  in  the  intestine,  consist  of  peristaltic 
and  pendular  motions.     Obviously,  the  contraction  of  the  circular 

1  Arch,  de  physiol.,  norm,  et  path.,  1892,  also,  Doyon,  ibid.,  1895. 


1014  DIGESTION 

fibers  must  constrict  its  lumen,  whereas  the  contraction  of  the  longi- 
tudinal fibers  must  render  that  particular  segment  more  bulky  and 
enlarge  its  capacity.  Ordinarily,  however,  these  two  movements  are 
combined  into  what  is  known  as  the  peristaltic  wave,  which  consists  of 
a  zone  of  constriction  and  an  anteceding  zone  of  relaxation.  These 
peristaltic  waves  may  proceed  either  from  above  downward  or  from 
below  upward.  The  former  constitute  the  regular  peristaltic  waves 
and  the  latter,  the  antiperistaltic  leaves.  We  shall  see  later  that  anti- 
peristalsis  is  the  chief  movement  of  the  beginning  portion  of  the  large 
intestine,  while  regular  peristalsis  is  the  principal  movement  of  the 
small  intestine.  Antiperistalsis  is  observed  here  only  under  abnormal 
conditions.  A  second  type  of  movement  executed  usually  by  the  small 
intestine,  is  the  so-called  pendular  motion.  It  consists  of  alternate 
constrictions  and  relaxations  of  neighboring  segments  of  the  gut,  which 
are  repeated  with  a  definite  regularity  or  rhythm. 


Fig.  515. — Diagram  to  Show  the  Effect  of  the  Rhythmical  Constricting  Move- 
ments OF  THE  Small  Intestine  cpon  the  Contained  Food. 
A  string  of  food  (1)  is  divided  suddenly  into  a  series  of  segments  (2);  each  of  the 
latter  is  again  divided  and  the  process  is  repeated  a  number  of  times  (3  and  4).  Even- 
tually a  peristaltic  wave  sweeps  these  segments  forward  a  certain  distance  and  gathers 
them  again  into  a  long  string  ,  as  in  (1).  The  process  of  segmentation  is  then  repeated 
as  described  above.     (Cannon.) 

When  the  chyme  is  ejected  into  the  duodenum,  it  is  forced  against 
the  upper  surfaces  of  the  valvulse  conniventes  which  stretch  across  the 
lumen  of  the  subpyloric  canal  in  the  form  of  incomplete  transverse 
partitions.  In  consequence  of  this  initial  impediment  to  its  rapid 
onward  flow,  the  chyme  is  collected  in  a  single  mass  well  above  the 
orifices  of  the  biUary  and  pancreatic  ducts.  Now  begins  its  subdivision 
into  smaller  portions  by  the  pendular  or  rhythmic  movements.  A 
comprehensive  study  of  these  has  been  made  by  Griitzner^  who  was 
able  to  analyze  them  by  mixing  insoluble  substances,  such  as  nitrate 
of  bismuth,  with  the  ingesta.  More  recently.  Cannon^  has  studied 
them  with  the  help  of  the  Rontgen  rays.  Constrictions  appear  here 
and  there  which  split  the  formerly  large  mass  into  numerous  smaller 
ones.  Moreover,  these  constrictions  appear  in  a  perfectly  I'egular  order 
so  that  the  original  mass  is  divided  first  into  two,  then  into  four,  then 
into  eight,  and  more.     These  smaller  portions  are  then  reunited  into 

1  Pfluger's  Archiv,  Ixxi,  1898. 

2  Am.  Jour,  of  Physiol.,  i,  1898,  and  vi,  1902. 


THE    MECHANICS    OF    DIGESTION  lOlT) 

larger  ones.  This  rhytlunic  play  continues  for  some  time  at  the  rate 
of  20  to  30  in  a  minute  (cat)  until  the  chyme  has  been  thoroughly  mixed 
with  the  intestinal  secretions,'  and  naturally,  the  cessation  of  those 
alternate  constrictions  and  relaxations  must  leave  the  now  rather 
liquid  material  again  reunited  into  a  single  mass.  A  regular  peristaltic 
wave  then  sweeps  it  onward  into  a  lower  segment  of  the  small  intestine, 
where  the  pendular  movements  are  repeated  with  the  same  result. 
While  this  mechanical  and  chemical  reduction  of  the  food  is  continued 
far  into  the  ileum,  the  material  alnvidy  reduced  is  absorbed;  in  fact, 
absorption  begins  very  soon  after  the  entrance  of  the  chyme  into  the 
duodenum  and  reaches  its  height  in  the  jejunum  and  upper  ileum.  In 
the  lower  ileum,  on  the  other  hand,  most  of  the  assimilable  material 
has  already  been  removed,  but  naturally,  much  depends  upon  the 
character  of  the  ingesta,  and  the  tonicity  of  the  intestinal  musculature. 

It  should  also  be  noted  that  the  peristalsis  and  pendular  motion 
undoubtedly  facilitate  absorption  in  a  mechanical  way,  because  they 
tend  to  increase  the  flow  of  the  lymph  and  blood.  Secondly,  they  tend 
to  bring  the  individual  villi  into  a  more  intimate  relation  with  the 
intestinal  contents.  As  far  as  the  regular  peristaltic  wave  is  concerned, 
it  should  be  mentioned  that  it  occurs  in  two  forms,  namely,  as  a  slowly 
advancing  contraction  (2  to  3  cm.  per  sec.)  which  again  disappears  at 
a  distance  of  about  5  cm.  from  its  place  of  origin,  and  as  a  more  rapid 
contraction  which  may  cover  a  distance  of  10  to  15  cm.  and  more. 
The  former,  therefore,  remains  more  localized  and  serves  to  disseminate 
the  material  so  that  it  may  be  acted  upon  later  on  by  the  pendular 
motions.  The  latter,  on  the  other  hand,  serves  to  remove  the  com- 
pletely digested  material  into  more  distant  segments  situated  nearer 
the  ileocecal  valve.  No  definite  statements  can  be  made  regarding  the 
degree  of  pressure  which  may  be  developed  by  these  waves,  but  since 
the  fecal  material  is  in  a  liquid  state,  it  may  be  surmised  that  the  energy 
required  to  move  it  is  very  slight.  This  deduction  is  upheld  by  the 
experiments  of  Cash^  which  show  that  a  weight  of  5  to  8  gm.  applied 
to  the  surface  of  the  intestines,  suffices  to  block  the  progress  of  the 
feces. 

Antiperistaltic  movements  occur  in  the  small  intestine  only  under 
abnormal  conditions,  such  as  may  arise  in  consequence  of  obstructions 
by  foreign  bodies  and  tumors,  or  as  a  result  of  an  invagination  or 
kinking  of  the  entire  gut.  If  the  lesion  is  a  high  one,  the  fecal  mate- 
rial is  often  forced  into  the  stomach,  whence  it  is  expelled  by  the  proc- 
ess of  vomiting. 

The  Nervous  Control  of  the  Intestinal  Movements. — While  these 
peristaltic  movements  may  be  evoked  almost  anywhere  along  the  intes- 
tine, they  begin  as  a  rule  high  up  in  the  duodenum,  and  hence,  it  would 
not  be  incorrect  to  speak  of  a  "pace-maker"  of  peristalsis.  In  all 
these  instances,  the  stimulations  are  local  in  their  character  and  may 

1  Magnus,  Pfluger's  Archiv,  cxi,  1906,  152. 

2  Proc.  R.  Soc,  London,  1887. 


1016  DIGESTION 

he  brought  to  bear  either  upon  the  muscle  tissue  or  upon  the  nervous 
tissue.  The  early  experiments  of  Bayliss  and  Starling^  have  led 
strength  to  the  first  view,  which  is  embodied  in  the  so-called  myogenic 
theory  of  the  origin  of  peristalsis,  because  it  could  be  shown  that  the 
application  of  nicotine  does  not  destroy  these  movements.  The 
experiments  of  Cohnheim^  and  Magnus,^  on  the  other  hand,  favor  the 
neurogenic  theory,  which  holds  that  the  nervous  tissue  is  the  recipient 
element.  Thus,  it  was  found  that  isolated  segments  exhibited  these 
movements  even  after  the  removal  of  their  mucosa  and  submucosa, 
and  that  the  separation  of  the  inner  and  outer  coats  of  muscle  tissue 
destroyed  them  only  in  that  layer  which  was  disconnected  from  the 
plexus  of  Auerbach.  In  addition,  Yanase^  has  shown  that  the  intes- 
tines of  the  embryo  rabbit  and  human  fetus  do  not  begin  to  move 
until  the  aforesaid  nervous  elements  have  made  their  appearance. 

While  this  controversy  seems  to  favor  the  neurogenic  theorj^  it 
may  be  best  to  confine  ourselves  for  the  present  to  the  statement  that 
the  peristaltic  movements  result  in  consequence  of  the  stimulation  of 
the  intestine  by  the  fecal  material  and  that  they  may  arise  in  any  one 
of  its  different  segments.  The  result  is  a  diphasic  wave,  consisting  of  a 
zone  of  constriction  which  is  anteceded  by  a  zone  or  relaxation.  Con- 
sequently, the  peristaltic  movement  represents  a  true  reflex  response 
which  is  made  possible  by  the  coordinated  action  of  the  local  nervous 
mechanism.  The  latter  may  in  turn  be  influenced  by  afferent  impulses 
arising  in  other  parts  of  the  bodj^,  because  it  is  a  matter  of  common 
experience  that  emotions  or  sensory  impressions  of  different  kinds 
may  inhibit  or  accelerate  the  activity  of  the  intestinal  musculature. 
These  impulses,  in  all  probabilitj^,  descend  through  the  vagus  system 
and  terminate  in  the  mesenteric  ganglion  of  the  solar  plexus,  whence 
they  are  relayed  to  the  intra-intestinal  mechanism  by  way  of  the  mes- 
enteric plexus.  Regarding  the  latter,  it  has  been  proved  by  Burton- 
Opitz^  that  it  contains  efferent  as  well  as  afferent  fibers  for  the 
intestine.  The  fact  that  the  vagus  nerve  constitutes  the  preganglionic 
path  of  these  musculomotor  impulses  seems  definite^  proved,  because 
its  stimulation  evokes  strong  contractions  of  the  intestine.  The  claim 
that  the  splanchnic  nerve  is  the  musculo-inhibitor  nerve  of  the  intes- 
tine, need  not  be  discussed  at  length,  because  it  lacks  a  satisfactory 
experimental  basis.  As  has  been  stated  above,  the  flaccidity  of  parts 
ensuing  in  consequence  of  the  stimulation  of  this  nerve,  may  be  due  to 
its  vasoconstrictor  action  and  the  anemia  resulting  therefrom.  To 
summarize:  (a)  the  intestine  is  in  possession  of  a  local  nervous  mech- 
anism which  renders  it  relatively  independent  of  the  central  nervous 
system,  (6)  systemic  reflexes  are  made  possible  by  the  communications 

1  Jour,  of  Physiol.,  xxvi,  1901,  125. 

2  Zeitschr.  fur  Biol.,  xxxii,  1899. 

3  Ergebn.  der  Physiol,  1908. 

«  Pfluger's   Archiv,   cxix,  1907,  451. 
6  Ibid.,  cxxxv,  1910,  245. 


THE    MECHANICS    OF    DIGESTION 


1017 


existing  botAvccn  this  syinpatiu^tic;  nullification  and  central  jjarts  Ijy 
way  of  the  mesontoric  ganglion  of  the  solar  plexus  and  the  vagi  nerves, 
and  (c)  the  siieeessive  segments  of  the  intestine  are  enabled  to  act  in 
unison,  because^  the  plexus  of  Meissner  and  Auerbaeh  is  arranged  in 
the  form  of  successive  reflex  circuits  which  arc  correlated  with  one 
another. 

The  last  contention  is  based  upon  the  experimental  evidence  that 
peristaltic  waves  may  be  incited  almost  anywhere  along  the  intestine 
which  then  progress  in  a  downwartl  direction  through  its  successive  seg- 
ments. Additional  hght  has  been  thrown  upon  this  question  by  Mall 
who  has  resected  and  reversed  certain  segments  of  the  small  intestine  so 
that  their  formerh'  lower  ends  became  their  upper.  At  autopsy,  these 
animals  invarial)ly  exhibited  a  fusiform  distention  of  th(;  intestine  above 
the  line  of  the  upper  suture  and  an  accumulation  of  fecal  material 
which  in  many  cases  had  resulted  in  necrosis,  perforation,  and  peri- 
tonitis. It  is  evident,  therefore,  that  this  in- 
version of  an  intestinal  loop  causes  the  regular 
peristalsis  to  cease  at  the  upper  line  of 
sutures.  Moreover,  if  an  oval  ball  of  wood 
is  inserted  into  the  upper  end  of  one  of  these 
inverted  segments,  it  is  again  expelled 
through  the  same  opening,  whereas  its  inser- 
tion through  the  lower  orifice  gives  rise  to  a 
peristaltic  wave  which  moves  it  in  the  direc- 
tion of  the  stomach.  The  question  of 
whether  the  intestinal  movements  of  man 
can  at  all  be  compared  with  those  of  other 
animals,  may  be  answered  in  the  positive; 
in  fact,  Carvallo,  as  well  as  Kiipferli^  state 
that  they  are  identical. 

The  Movements  of  the  Large  Intestine. 
— The  function  of  the  large  intestine  is  so 
widely  different  from  that  of  the  small  intes- 
tine that  these  two  parts  may  almost  be 
considered  as  separate  organs.     In  the  car- 

nivora  the  process  of  digestion  and  absorption  is  practically  completed  at 
the  ileocecal  valve,  while  in  the  herbivora  these  processes  continue 
in  all  their  intensity  distally  to  this  point.  The  omnivora  occupy  an 
intermediate  position,  but  since  the  human  large  intestine  is  relatively 
long  and  possesses  a  capacious  cecal  vestibule  and  peculiarly  indented 
colon,  it  more  nearly  resembles  that  of  the  herbivorous  animals. 
The  ileocecal  valve  is  a  sphincter  formed  of  a  heavj'  band  of  muscle 
tissue  and  two  membranous  flaps  which  are  unequal  in  size  and  do  not 
close  firmly.  The  fact  that  the  contents  of  the  cecum  may  be  forced 
back  into  the  ileum  with  great  ease,  shows  that  it  does  not  form  a  veiy 
efficient  sphincter.     At  the  same  time,  it  must  be  admitted  that  it 

1  Zeitschr.  flir  Rontgenkunde,  xiv,  1912. 


Fig.  516. — Diagraai  to 
Show  the  Position  of  the 
Ileocecal  Valve. 

J,  Ileum;  C,  cecum;  A, 
orifice  of  the  proc.  vermi- 
formis;  AC,  ascending  colon; 
H,  haustrum. 


1018 


DIGESTION 


impedes  the  progress  of  the  contents  of  the  ileum  sufficiently,  so  that 
the  latter  can  advance  into  the  cecum  only  in  larger  masses  and  under 
a  sHght  increase  in  pressure  effected  by  the  periodic  peristaltic  move- 
ments of  the  ileum. 

The  large  intestine  may  be  divided  into  four  parts,  namely,  the 
cecum  with  its  vermiform  appendix,  and  the  ascending  (proximal), 
transverse  (intermediate),  and  descending  (distal)  portions  of  the 
colon.  The  movements  observed  here  are  very  similar  to  those  pre- 
viously noted  in  the  upper  gut,  i.e.,  they  consist  of  peristaltic  and  pen- 
dular  motions.  It  is  to  be  emphasized,  however,  that  the  latter  are 
now  of  little  importance,  whereas  the  antiperistaltic  movements  are 
even  more  prominent  than  the  peristaltic.^  It  is  also  obvious  that 
the  large  intestine  is  much  more  quiescent  than  the  small  intestine,  a 


Fig.  517. — Shadows  of  the   Huil^n  L.\rge   Intestixe   Obtained  by   Means  of  the 

RoxTGEx    Rats. 
I,  Entrance  of  the  contents  of  the  ileum  into  the  cecum  and  colon.     II,  the  material 
has   progressed    through    the  transverse  colon  as  far  as  the  splenic  flexure,  some  has 
escaped  into  rectum.     Ill,  the  large  intestine  outlined  by  means  of  a  solution  of  sub- 
nitrate  of  bismuth  injected  through  the  rectum. 


fact  which  is  in  perfect  agreement  with  the  time  required  by  the  food 
to  traverse  this  channel.  To  illustrate,  while  the  human  stomach  and 
small  intestine  which  measure  about  7  m.  in  length,  retain  the  food  for 
only  about  7  to  9  hours,  the  large  intestine  which  is  only  1.5  m,  in 
length,  cannot  be  passed  in  a  much  briefer  time  than  20  hours.  Con- 
sequently, the  passage  of  the  food  from  the  mouth  to  the  anus  occu- 
pies in  all  from  25  to  30  hours.  An  active  alimentary  canal,  therefore, 
would  evacuate  its  contents  once  in  about  every  24  hours. 

On  entering  the  ascending  colon,  the  chj^me  incites  antiperistaltic 
waves  which  force  it  into  the  cecum.  A  regular  peristaltic  wave 
then  moves  it  upward  toward  the  hepatic  flexure,  whence  it  is  again 
thrown  back  into  the  cecum  by  the  antiperistalsis.  These  back  and 
forth  movements  continue  for  some  time  until  the  contents  have  lost 
most  of  their  water  and  gradually  escape  in  a  semisolid  state  into  the 
transverse  colon.  It  is  to  be  noted  especially  that  these  antiperistaltic 
motions  do  not  oppose  the  regular  waves,  but  alternate  with  them  and 

1  Jacobi,  Archiv  fiir  exp.  Path,  und  Pharm.,  xxvii,  1890. 


THE    MECHANICS    OF    DIGESTION  1019 

give  rise  to  a  harmonious  back  ami  fort  li  mot  ion  of  t  he  feces.  Further- 
more, since  the  proximal  colon  is  subdivided  into  successive  recesses 
by  incomplete  transverse  partitions,  a  whirlpool  effect  is  produced 
which  carries  the  contents  from  haustrum  to  haustrum.  It  is  for  this 
reason  tiiat  the  movements  in  the  proximal  colon  and  cecum  are  often 
designated  as  haustral  churning. 

Gradually  as  the  water  is  absorbed,  the  fecal  material  assumes 
a  more  solid  consistency  and  escapes  into  the  transverse  colon,  whereas 
its  more  fluid  portion  is  forced  back  into  the  cecum.  Eventually, 
however,  all  of  it  is  lodged  in  the  transverse  colon  and  is  held  here 
until  forced  into  the  rectum  by  long  and  forceful  peristaltic  waves. 
This  segment,  therefore,  plays  the  part  of  a  storehouse  and  hence,  it 
cannot  surprise  us  to  find  that  any  retardation  of  the  feces  must 
result  in  a  loss  of  an  excessive  quantity  of  water  and  a  firm  lodgment 
of  these  masses  in  the  haustrae.  Its  gradually  increasing  weight  then 
gives  rise  to  a  sagging  which  causes  the  hepatic  flexure  to  assume  a 
much  lower  level  than  the  splenic  flexure.  This  condition  is  not  at 
all  uncommon  and  is  responsible  for  the  peculiar  outline  of  this  part 
of  the  intestine  when  observed  with  the  Rontgen  rays.  It  then  dis- 
plays the  contours  of  a  snake  when  assuming  the  position  of  striking. 
The  descending  colon  and  rectum  are  usually  empty  and  are  filled  only 
a  short  time  before  the  beginning  of  the  act  of  defecation.^  This 
filling  of  the  rectum  is  accomplished  by  two  or  three  powerful  long 
peristaltic  waves  which  begin  in  the  transverse  colon  and  slowly  trav- 
erse the  descending  colon,  forcing  the  feces  into  the  rectal  receptacle. 
They  are  usually  accompanied  by  noises  which  have  been  designated  by 
Kussmaul  as  the  ''tormina  intestinorima."  In  accordance  with  Scharz,'' 
it  may  be  concluded  that  these  waves  are  the  direct  cause  of  defecation, 
because  they  force  a  certain  amount  of  fecal  material  into  the  rectmn 
which  then  serves  as  the  initial  stimulus  to  the  receptors  initiating  this 
process. 

Cannon^  divides  the  large  intestine  into  two  parts,  the  first  of 
which  includes  the  very  active  cecum  and  ascending  colon  and  the 
second,  the  relatively  inactive  transverse  and  descending  colons. 
This  line  of  demarcation  transects  it  distally  to  the  hepatic  flexure. 
Furthermore,  Elliott  and  Barclay-Smith'*  have  shown  that  the  intense 
antiperistaltic  movements  of  the  upper  large  intestine  are  present  in 
a  great  variety  of  animals,  and  are  especially  prominent  in  the  her- 
bivora  in  which  the  cecum  plays  the  part  of  a  large  thin-walled 
reservoir  for  the  food  while  undergoing  bacterial  decomposition. 

Defecation. — The  distal  portion  of  the  colon  leads  into  the  sigmoid 
flexure   and   rectum.     Under  normal   conditions,   the  latter  receives 

1  Roith,  Anat.  Hefte,  1902,  and  Reider,  Fortschr.  auf  dem  Geb.  der  Rontgen- 
strahlen,  1912. 

2  Miinchener  med.  Wochenschr.,  1911. 

3  Am.  Jour,  of  Physiol.,  xxix,  1911,  238. 
*  Jour,  of  Physiol.,  xx.xi,  1904,  272. 


1020 


DIGESTION 


fecal  material  verj'  shortly  after  arising,  because  the  food  which  has 
found  lodgment  in  the  transverse  colon  during  the  preceding  night, 
is  then  aided  by  gravity  and  a  renewed  irritability  of  the  receptors 
in  exciting  those  long  peristaltic  waves  which  finally  move  it  into  the 
vicinit}'  of  the  anal  orifice.  The  gradually  increasing  mass  of  rectal 
contents  finall}-  stimulates  the  mucosa  in  a  mechanical  manner  and 
evokes  those  muscular  responses  which  are  required  for  its  expulsion. 
If  the  feeling  of  fulness  experienced  at  this  time,  is  neglected,  the  walls 
of  the  rectum  relax  more  fully,  so  that  a  much  greater  excitation  will 
be  required  to  make  them  contract  again.     In  man,  Hertz'  has  shown 


Jymfsatfi9^ic  yrvnk 


nwa  ffypcyai/f-/uis 

Fig.  518. — Schema  to  Show  the  Ivntehvatiox  of  'i-he  Rectum  axd.  Internal  Sphinc- 
ter OF  THE  Anus,  and  the  Formation  of  the  Hypogastric  Plescus.  {After  Frankl- 
Hochu-art  and  Frohlich.) 

that  the  intrarectal  pressure  may  rise  to  30  and  40  mm.  Hg.  before  the 
act  of  defecation  is  actually  initiated. 

While  defecation  is  a  reflex  phenomenon,  it  also  embraces  a  definite 
voluntary  factor.  The  former  consists  in  peristaltic  contractions  of 
the  rectum  and  the  inhibition  of  the  internal  sphincter,  whereas  the 
latter  comprises  the  relaxation  of  the  external  sphincter  and  the  activa- 
tion of  the  abdominal  press.  Under  normal  conditions,  these  reflexes 
may  be  counteracted  if  necessary,  by  volition,  but  only  until  the  sen- 
sory stimuli  become  so  powerful  that  they  are  able  to  overcome  the 
volitional  efforts.  The  reflex  center  for  defecation  is  situated  in 
the  lumbar  segment  of  the  spinal  cord,  whence  efferent  and  afferent 

»  Guy's  Hosp.  Rep.,  1907. 


THE    MECHANICS    OF    DIGESTION  1021 

nerve  fibers  pass  to  the  imisculature  of  tlie  reetuin  anrl  the  internal  and 
exteruaJ  sphincters.  By  means  of  these  channels,  this  center  is 
brought  into  functional  re'ation  with  ditTerent  local  receptors  which 
may  either  augment  or  inhibit  its  activity.  In  the  latter  case,  the 
sphinct(>rs  are  relaxed.  It  is  connected  with  the  cerebrum  by  means 
of  different  afferent  and  efferent  paths,  so  that  volition,  emotions,  and 
various  sensory  impulses,  may  be  brought  to  bear  upon  it. 

The  powerful  band  of  smooth  muscle  tissue  forming  the  internal 
sphincter,  receives  its  motor  supply  from  the  hypogastric  plexus  by  way 
of  the  nervus  erigens,  and  its  inhibitory  supply  from  the  sam(;  source 
by  way  of  hypogastric  nerve.  These  nerves  also  embrace  sensory 
fibers  from  the  same  region,  as  well  as  sensory  and  motor  fibers  for 
the  rectum.  When  severed,  the  excitation  of  the  central  end  of  the 
nervus  (>rigens  gives  rise  to  an  inhibitory  effect  which  is  made  possible 
with  the  help  of  the  hypogastric  nerve.  Quite  shnilarly,  the  stimula- 
tion of  the  central  end  of  the  divided  hypogastric  nerve  produces 
motor  results  through  the  intervention  of  the  nervus  erigens.^  The 
external  sphincter  is  composed  of  striated  muscle  tissue  and  is  inner- 
vated by  the  nervi  hemorrhoidales  inferiores  which  are  derived  from 
the  nervus  pudcndus  and  sacral  spinal  nerves.  This  muscle  acts  in 
unison  with  the  levator  ani  and  other  perineal  muscles,  and  aids  in 
restoring  the  everted  mucous  membrane  of  the  anus  after  the  completion 
of  defecation. 

1  Frankl-Hochwart  and  Frohlich,  Pfluger's  Archiv,  Ixxxi,  1900,  420. 


SECTION  XXVII 
ABSORPTION 


CHAPTER  LXXXV 

THE  ABSORPTION  OF  THE  REDUCED  FOODSTUFFS  FROM 
THE  ALIMENTARY  CANAL 

General  Discussion. — The  term  absorption  refers  more  particu- 
larly to  the  process  bj^  means  of  which  the  simplified  foodstuffs  are 
transferred  from  the  Imnen  of  the  aUmentary  canal  into  the  absorbing 
channels,  i.e.,  into  the  blood-capillaries  or  the  lacteals.  It  is  to  be 
remembered,  however,  that  certain  animals  also  take  in  materials 
through  their  skin,  and  that  absorption  from  the  different  body-cavi- 
ties is  a  common  phenomenon.  If  we  confine  ourselves  at  this  time 
to  the  foodstuffs,  it  is  to  be  noted  first  of  all  that  water,  salts,  and  the 
simple  sugars  are  dialyzable  without  digestion,  whereas  others  must 
be  changed  so  as  to  be  able  to  pass  through  the  intestinal  epithelium. 
This  brings  in  a  definite  element  of  time;  digestion  and  absorption 
going  on  side  by  side,  because  certain  substances  begin  to  pass  into  the 
body  long  before  the  chemical  and  mechanical  reductions  of  all  the 
different  foodstuffs  have  actually  been  completed.  Moreover,  while 
some  of  the  digested  material  may  be  taken  up  in  the  mouth,  stomach, 
and  large  intestine,  by  far  the  largest  amount  is  absorbed  in  the  small 
intestine. 

In  endeavoring  to  obtain  an  idea  regarding  the  factors  concerned 
in  absorption,  we  find  first  of  all  that  they  are  resident  in  a  layer  of 
epithelial  cells,  which,  physiologically  considered,  really  form  a  part 
of  the  external  envelope  of  the  body.  Through  these  the  simplified 
foodstuffs  must  pass  in  order  to  gain  access  to  the  fluids  of  the  body. 
Until  not  so  many  years  ago  it  was  believed  that  the  forces  by  means  of 
which  this  transfer  is  effected,  consist  of  filtration,  diffusion,  and 
osmosis.  In  the  course  of  time,  however,  it  has  become  evident  that 
many  of  these  phenomena  cannot  be  explained  upon  this  basis 
and  hence,  physiologists  finally  took  recourse  to  a  purely  vitalistic 
hypothesis.  As  emphasized  repeatedly  on  previous  occasions,  it  is  for 
us  to  accept  an  intermediate  view  which  not  only  acknowledges  the 
above  phj^sical  principles,  but  also  recognizes  the  occurrence  of  certain 
intracellular  processes,  regarding  which  our  knowledge  is  as  yet  ex- 

1022 


THE    ABSOlil'TlON    OF    THE    llEDUCED    FOODSTUFFS         1023 


tremoly  imperfect .  The  hitter  consist  in  inicrophysical  and  micro- 
chemical  reactions  and  not  in  phenomena  which  might  more  riglitly 
find  a  phice  in  metaphysics.  Whik'  the  work  in  molecular  physics, 
such  as  that  of  DeVries,  Van't  Hoff  and  Fischer,  has  gone  far  to  clear 
up  the  nature  of  these  processes,  it  must  be  admitted  that  our  explana-^ 
tions  are  still  based  ujion  generalities. 

Dififusion,  Osmosis,  Dialysis. — The  term  diffusion  is  applied  to 
the  spreading  about  or  scattering  of  molecules  through  media  allowing 
this  movement.  Thus,  if  a  solution  of  a  salt  is  placed  in  a  receptacle 
and  a  layer  of  water  is  carefully  allowed  to  run  over  it,  it  Avill  be  found 
after  a  thne  that  a  certain  number  of  the  mole- 
cules of  the  salt  have  entered  the  overlying 
water  and  have  established  a  medium  of  uniform 
composition  throughout.  This  spreading  out 
also  takes  place  if  two  solutions  of  different 
salts  are  brought  into  contact  with  one  another. 
A  uniform  mixture  is  the  final  result.  Next  we 
proceed  to  interpose  between  the  solution  and 
the  water  an  animal  membrane,  such  as  a 
piece  of  intestine,  urinary  bladder,  swim- 
bladder,  or  an  artificial  membrane  made  by 
allowing  ferrocyanide  of  potassium  to  come  in 
contact  with  cupric  sulphate  in  an  unglazed 
piece  of  porcelain.  The  result  of  this  interac- 
tion is  a  layer  of  ferrocyanide  of  copper.^  Such 
membranes  may  be  absolutely  impermeable, 
completely  permeable,  or  partially  permeable 
to  water  and  its  constituents.  The  first  allows 
no  diffusion  at  all,  whereas  the  second  permits 
it  to  occur  freely  in  both  directions.  This 
narrows  this  discussion  down  to  membranes  of 
semi-permeable    character,    namely,    to    those 


ii-nigSO^: 


R- 


Fig.  519. — A  Simple 

Osmometer. 
The  receptacle  contains 
water,  and  the  cell  a  solu- 
,  .    ,       n  »  •     .         ,  »         /        1      ,         i     tion  of  mag  nesium  sul- 

which  allow  a  tree  interchange  ot  water  but  not  phate.  As  the  molecules 
of  the  dissolved  substances.  Consequently,  if  of  water  are  drawn  through 
the  water  and  the  salt  solution  are   separated  ^^"^  semi-permeable  mem- 

,,.,.,,  ,    ^  .  ,   brane,    the    level    of    the 

by  a  membrane  of  this  kind,  the  molecules  of  MgS04  solution  rises, 
water  will  gradually  pass  through  its  pores  into 

the  solution.  This  phenomenon  is  called  osmosis.  Quite  similarly, 
we  may  fill  a  thistle  tube  with  a  solution  of  magnesium  sulphate, 
close  its  large  orifice  with  an  animal  membrane,  and  place  it  in  water 
so  that  the  level  of  the  latter  corresponds  precisely  with  that  of  the 
said  solution.  Water  then  passes  into  the  thistle  tube,  causing  the 
level  of  the  magnesium  sulphate  solution  to  rise  until  its  height  indicates 
a  considerable  back  pressure  against  the  membrane.     This  pressure 

1  Morse  and  Frazer,  Am.  Chem.  Jour.,  xxxiv,  1905,  1,  also  Hedin,  Pfltiger's 
Archiv,  Ixxviii,  1899,  205,  Hober,  ibid.,  Ixxi,  1898,  624,  and  Denis,  Am.  Jour,  of 
Physiol.,  xvii,  1906,  35. 


1024 


ABSORPTION 


which  is  known  as  the  osmotic  pressure,  is  responsible  for  the  passage 
("pulHng")  of  the  molecules  of  water  through  the  pores  of  the  mem- 
brane. In  general,  it  may  be  said  that  the  osmotic  pressure  of  a  solu- 
tion is  proportional  to  its  molecular  concentration,  i.e.,  to  the  number 
of  molecules  of  the  dissolved  substance  in  a  given  volume  of  the  solu- 
tion. This  fact  implies  that  it  differs  with  the  character  of  the  solu- 
tions employed.  Its  force,  however,  is  considerable  at  all  times. 
Thus,  it  has  been  determined  that  a  1.0  per  cent,  solution  of  cane- 
sugar  at  0°C.  exerts  a  pressure  of  493  mm.  Hg.  Regarding  its  origin 
little  is  known,  but  it  is  commonly  believed  that  it  is  due  to  the 


Fig.  520. — Dialyser,  Consisting  of  a  Tube  of  Parchment  Paper  Immersed  ina  Ves- 
sel THROUGH  Which  a  Constant  Stream  of  Sterile  Distilled  Water  can  be  Passed. 
( Wroblcski.) 

kinetic  energy  of  the  moving  molecules.     The  greater  their  attraction, 
the  greater  this  pressure. 

While  such  simple  arrangements  as  have  just  been  described, 
actually  exist  in  our  body,  the  most  common  interchanges  take  place 
between  crystalloids  and  colloids.  The  process  of  transferring  these 
substances  through  an  animal  membrane  interposed  between  the 
solution  containing  them  and  the  water,  is  known  as  dialysis.  In 
this  case,  the  crystalloids  traverse  the  membrane  and  enter  the  water, 
while  the  colloids  do  not.  But  since  the  membranes  in  our  body  are 
only  approximately  semi-permeable,  they  allow  water  to  go  through 


THE    ABSORPTION    OF    THE    REDIT'EI)    FOODSTUFFS         1025 

with  ease  and  besides,  also  the  suljstances  in  sohitiun.  I'hc  hitter,  liow- 
ever,  pass  with  much  greater  cUfficulty.  For  this  reason,  the  osmotic 
flow  of  water  to  tlie  side  of  the  crystalloid  is  associated  with  a  passage 
of  the  molecules  of  the  latter  into  the  water  on  the  other  side  of  the 
membrane.  These  counter  streams  eventually  lead  to  an  equalization 
of  the  concentration  of  the  fluids  on  the  two  sides  of  the  membrane, 
as  well  as  to  an  equalization  of  the  osmotic  pressure  and  a  cessation  of 
the  osmosis.     Only  difTusion  then  continues  in  both  directions. 

The  osmotic  pressure  of  a  solution  may  be  calculated  by  ascertain- 
ing the  amount  of  the  substance  present  in  it  and  the  degree  of  the 
dissociation  of  its  electrolytes.  A  much  simpler  method  is  to  deter- 
mine its  freezing  point,  because  the  freezing  point  of  water  is  lowered 
by  substances  held  in  solution,  and  the  degree  of  lowcM-ing  is  propor- 
tional to  the  molecules  and  ions  present  in  it.  A  comparison  of  the 
osmotic  pressures  of  different  solutions  may  be  made  by  noting  their 
influence  upon  certain  vegetable  and  animal  cells.  ^  Thus,  if  erythro- 
cytes are  brought  in  contact  with  the  solution  to  be  tested,  they  either 
swell,  or  shrink,  or  remain  normal.  Inasmuch  as  these  cells  are  ordi- 
narily contained  in  blood  plasma,  this  medium  must  be  isotonic  to 
them,  i.e.,  it  must  possess  the  same  osmotic  pressure  as  the  red  cor- 
puscles. No  osmotic  interchanges  then  take  place.  It  may,  therefore, 
be  reasoned  that  any  solution  in  which  they  retain  their  normal  size 
and  shape,  is  isosmotic  or  isotonic  to  them  as  well  as  to  the  blood 
plasma.  A  hyperosmotic  or  hypertonic  solution  is  one  possessing 
a  greater  osmotic  pressure,  and  a  hyposmotic  or  hypotonic  solution,  one 
possessing  a  slighter  osmotic  pressure  than  these  cells  or  the  blood- 
serum.  In  the  first  instance,  these  cells  will  lose  water  and  shrink 
and  in  the  latter,  acquire  water  and  swell  up.^ 

Electrol3rtes. — The  law  of  osmosis  as  previously  stated,  is  prac- 
tically identical  with  the  law  of  Boyle  pertaining  to  the  diffusion  of 
gases.  The  latter  states  that  the  pi-essure  of  a  gas  is  proportional  to 
its  density,  i.e.,  to  the  number  of  the  molecules  in  a  given  volume  of 
the  gas.  Like  the  osmotic  pressure,  the  gaseous  pressure  remains  pro- 
portional to  the  absolute  temperature  and  the  sum  of  the  partial 
pressures  of  the  constituents  of  the  mixture.  A  slight  discrepancy  be- 
tween gas  pressure  and  osmotic  pressure,  however,  is  produced  by 
the  fact  that  the  molecules  of  many  substances,  when  in  solution,  are 
dissociated  into  two  or  more  parts  which  are  designated  as  ions.  These 
ions  are  charged  electrically  and  may  be  made  to  arrange  themselves 
in  accordance  with  their  potential  by  passing  an  electrical  current 
through  the  solution.  Thus,  it  will  be  found  that  sodium  chlorid 
gives  rise  to  Na  ions  and  CI  ions,  the  former  being  positive  and  the 
latter  negative.  If  an  electrical  current  is  now  passed  in  a  definite 
direction  through  this  solution,   these  ions  migrate  until  a  perfect 

1  McClendon,  Physical  Chemistry  and  Vital  Phenomena,  1917,  and  Bayliss, 
Principles  of  Gen.  Physiology,  1915.  • 

-  Overton,  Nagel's  Handb.  der  Physiologie,  1907. 


102G  ABSORPTION 

electrical  series  has  been  established  by  the  alternate  position  of  plus 
and  minus  elements.  Water,  on  the  other  hand,  is  not  easily  dissoci- 
ated and  hence,  cannot  serve  as  a  good  conductor  of  electricity.  The 
same  is  true  of  sugar.  Upon  these  differences  is  based  the  division 
of  substances  into  electrolytes  and  non-electrolytes.  Now,  since  an 
ion  plays  the  same  part  in  the  production  of  osmotic  pressure  as  a 
molecule,  it  will  be  seen  that  a  solution  of  an  electrolyte  must  exert 
a  proportionally  greater  osmotic  pressure,  because  it  contains  a  greater 
number  of  particles  consisting,  on  the  one  hand,  of  molecules  and,  on 
the  other,  of  ions. 

The  Diffusion  of  the  Proteins. — Conditions  in  our  body  are 
complicated  still  further  by  the  fact  that  its  different  fluids  do  not 
contain  solely  crystalloids,  but  also  other  substances,  such  as  proteins. 
The  latter  are  practically  indiffusible  through  animal  membranes, 
although  most  of  them  are  soluble  in  water,  weak  salt  solutions,  and 
dilute  acids  and  alkalies.  Moreover,  they  form  compounds  with 
metallic  salts,  acids  or  alkalies  and,  when  in  solution  or  pseudo-solution, 
can  be  converted  into  an  insoluble  form  by  various  simple  means, 
such  as  changes  in  the  reaction  and  temperature,  shaking,  and  the 
addition  of  neutral  salts.  By  reason  of  their  indiffusibility,  they  may 
be  separated  from  the  diffusible  crystalloid  substances  by  dialyzers, 
such  as  vegetable  parchment.  This  separation,  however,  cannot  be 
accomplished  without  difficulty. 

Considerable  progress  has  been  made  in  this  direction  more  recently  by  the 
work  of  J.  Loeb.i  It  has  been  shown  that  while  non-ionized  gelatin  may  exist  in 
gelatin  solutions  on  both  sides  of  the  isoelectric  point  (which  equals  an  hydrogen 
ion  concentration  of  CH  =  2.10"^  or  pH  =  4.7),  gelatin  when  it  ionizes,  can  only 
exist  as  an  anion  on  the  less  acid  side  of  its  isoelectric  point  (pPH>4.7)  and  as  a 
cation  only  ©n  the  more  acid  side  of  its  isoelectric  point  (pH>4.7).  At  the  iso- 
electric point  gelatin  can  dissociate  practically  neither  as  anion  nor  cation. 

On  the  acid  side  of  the  isoelectric  point  amphoteric  electrolytes  can  only  com- 
bine with  the  anions  of  neutral  salts,  on  the  less  acid  side  of  their  isoelectric  point 
with  cations;  and  at  the  isoelectric  point  neither  with  the  anion  nor  cation  of  a 
neutral  salt.  It  has  also  been  shown  that  the  isoelectric  point  of  an  amphoteric 
electrolyte  is  not  only  a  point  where  the  physical  properties  of  an  ampholyte  ex- 
perience a  sharp  drop  and  become  a  minimum,  but  that  it  is  also  a  turning  point 
for  the  mode  of  chemical  reactions  of  the  ampholyte.  It  is  suggested  by  Loeb 
that  this  chemical  influence  of  the  isoelectric  point  upon  life  phenomena  over- 
shadows its  physical  influence. 

Surface-tension. — Another  factor  which  no  doubt  plays  a  part 
in  absorption  is  surface-tension.  Its  action  may  be  illustrated  by 
placing  a  drop  of  water  upon  an  oily  surface  or  by  suspending  a  globule 
of  oil  in  a  fluid  with  which  it  does  not  readily  mix.  In  either  case, 
there  is  a  tendency  on  the  part  of  the  drop  to  assume  a  spherical  out- 
line. This  is  brought  about  by  the  fact  that  its  surface-layer  is  under 
a  certain  tension  which  tends  to  give  to  the  whole  as  small  a  surface  as 
possible,  and  naturally,  the  force  here  at  work  is  cohesion,  i.e.,  a 
mutual  attraction  between  its  constituent  molecules.  Supposing 
that  we  single  out  a  molecule  in  its  interior,  it  will  be  found  that  this 
1  Jour,  of  Gen.  Physiol.,  i,  1918,  39. 


THE    ABSOlfPTION    OF    THE    REDIU'EI)    FOODSTUFFS         1027 

unit  is  acted  upon  from  all  sides  by  llie  n('ighl)oriiifr  molecules,  and  that 
this  action  is  eciual  in  all  four  directions.  At  the  surface,  on  the  other 
hand,  conditions  are  difTerent,  because  iiere  the  molecules  are  not 
counterbalanced  by  a  tension  restinji;  upon  their  external  surfaces. 
Hence,  they  are  pulled  inward.  Now,  it  will  be  seen  that  if  the  drop  is 
surrounded  by  some  fluid,  its  suiface-molecules  must  be  acted  upon  by 
the  molecules  of  tlie  medium,  depending,  of  course,  upon  the  nature  of 
the  latter.  Obviously,  tliis  now  uneven  balance  must  give  a  different 
shape  to  the  drop  as  a  whole.  The  surface-tension  may  also  be 
altered  by  changes  in  temperature,  because  heat  tends  to  separate 
the  different  molecules  from  one  another  and  to  counteract  their 
power  of  attraction.  Cold,  on  the  other  hand,  increases  the  surface- 
tension,  because  it  brings  the  molecules  closer  together  by  removing 
from  them  the  kinetic  energy  necessary  for  expansion.  A  third  means 
by  which  the  surface-tension  may  be  altered,  is  the  electrical  current.^ 
Adsorption. — The  phenomenon  of  adsorption  may  be  illustrated 
by  exposing  a  solid  substance  in  powdered  form  to  a  solution  of  some 
kind.  The  dissolved  substance  then  accumulates  upon  the  surfaces 
of  the  sohd  particles  and  leaves  the  solution,  thereby  lessening  the 
concentration  of  the  latter.  This  property  is  well  displayed  by  the 
colloids  to  which  the  proteins,  with  the  exception  of  the  peptones,  be- 
long. Consequently,  since  our  body  contains  very  extensive  surfaces 
which  lie  in  relation,  on  the  one  hand,  with  the  body-fluids  and,  on 
the  other,  with  nutritive  material,  most  favorable  conditions  are 
estabUshed  for  the  occurrence  of  this  phenomenon.- 

A.  ABSORPTION  FROM  THE  INTESTINAL  CANAL 

The  Absorption  of  Water. — Water  and  the  ordinary  soluble  salts 
are  absorbed  unchanged,  but  the  quantity  which  actually  finds  its 
way  into  the  body,  depends  upon  the  intake  and  how  greatly  the 
system  is  in  need  of  it.  Since  water  is  lost  constantly,  because  it 
serves  as  a  medium  for  our  secretions  and  excretions,  correspondingly 
large  quantities  of  it  must  be  consumed  in  order  to  make  up  for  this 
loss.  In  a  way,  therefore,  it  may  be  said  that  the  body  is  in  water- 
equilibrium,  and  it  makes  little  difference  whether  a  man  takes  in  one 
liter  or  six,  because  any  superfluity  is  soon  compensated  for  by  a 
greater  discharge,  chiefly  through  the  kidneys.  Quite  similarly,  any 
scarcity  is  equalized  by  a  corresponding  reduction  in  the  quantity  of 
the  secretions  and  excretions.  In  the  latter  case,  however,  a  physio- 
logical limit  is  soon  reached,  at  which  the  phenomenon  of  tissue-thirst 
arises  as  a  means  of  safety.  The  body  also  possesses  the  power  of 
guarding  itself  against  too  large  an  intake,  because  unusually  large 

1  Macallum,  Ergebn.  der  Physiol.,  xi,  1911,  598;  also:  Traube,  Pfliiger's  Archiv, 
cv,  1904,  559. 

-Hofmann,  Zentralbl.  fiir  Physiol.,  xxiv,  1910,  805;  Robertson,  Jour.  Biol. 
Chem.,  iv,  1908,  35;  and  Van  Slyke,  ibid.,  iv,  1908,  259. 


1028  ABSORPTION 

quantities  of  water  give  rise  to  mechanical  reflexes,  nausea,  irritations 
of  the  gastric  and  intestinal  mucosa,  and  certain  symptoms  associated 
with  hydremic  plethora. 

One  of  the  reasons  for  the  relative  ease  with  which  the  system  may 
be  surcharged  with  water  is  that  the  alimentary  surface  is  not  suffi- 
ciently resistant  to  counteract  and  to  prevent  osmosis.  Moreover, 
while  the  excessive  intake  of  water  may  eventually  cause  the  feces 
in  the  large  intestine  to  become  watery,  this  channel  offers  a  certain 
resistance  to  its  escape  which  it  avoids  by  passing  through  the  epithe- 
lium. At  least,  this  is  the  tendency  in  most  persons.  Thus,  it  is  a  matter 
of  common  experience  that  constipation  is  usually  associated  with  a 
disincKnation  to  take  much  water,  and  as  much  as  3  to  5  liters  may  be 
absorbed,  before  the  feces  actually  assume  a  fluid  consistency.  The 
absorption  of  water  is  most  intense  in  the  small  intestine,,  but  some  of 
it  also  passes  over  into  the  cecum,  because  in  this  segment  the  fluid 
ileac  contents  are  gradually  changed  into  the  semi-solid  feces.  Under 
normal  conditions  the  stomach  does  not  allow  an  appreciable  quantity 
of  water  to  pass  through,  although  slight  amounts  of  peptones,  sugar, 
and  certain  drugs  may  be  absorbed  from  its  cavity.^  It  is  for  this 
reason  that  stenosis  of  the  pylorus  and  dilatation  of  the  stomach  are 
usually  accompanied  by  tissue-thirst,  which  cannot  be  relieved  by 
drinking.  As  far  as  the  channel  of  absorption  is  concerned,  it  has 
been  observed  that  the  introduction  of  salt  solutions  into  the  small 
intestine  does  not  increase  the  flow  of  Ij-mph  from  the  thoracic  duct, 
whereas  large  quantities  of  water  frequently  bring  about  a  dilution 
of  the  portal  blood.  It  is  probable,  therefore,  that  these  foodstuffs 
pass  directly  into  the  blood-stream  and  not  into  the  lacteals  and  lym- 
phatic system. 

The  osmotic  interchanges  betu-een  the  intestinal  contents  and  the 
blood,  may  be  illustrated  in  the  following  manner.  A  section  of  the 
small  intestine  of  an  etherized  mammal  is  drawn  through  a  wound  in 
the  abdominal  wall.  Two  loops  of  equal  size  are  then  marked  off 
bj^  three  ligatures.  Into  one  of  these  a  quantity  of  normal  saline 
solution  is  injected  which  thoroughly  distends  its  walls.  Into  the 
other,  a  few  drops  of  a  concentrated  solution  of  magnesium  sulphate 
are  injected.  Having  replaced  these  loops  in  their  proper  place  in 
the  abdominal  cavity,  the  animal  is  allowed  to  rest  for  about  one  hour. 
At  the  end  of  this  time,  it  will  be  found  that  the  loop  containing  the 
saline  solution,  is  now  practically  empty,  wliile  the  formerly  perfectly 
flabby  loop  containing  the  magnesium  sulphate,  is  highly  distended. 
This  experiment  clearl}^  shows  that  the  saline  solution  acts  as  a  hypo- 
tonic solution,  and  the  magnesium  sulphate  solution  as  a  hypertonic 
solution.  In  the  former  case,  water  is  removed  from  the  intestinal 
canal,  and  in  the  latter,  from  the  blood.  This  is  the  picture  of  saUne 
catharsis,  because  the  introduction  of  such  solutions  as  citrate  of  mag- 

1  Moritz,  Zeitschr.  fur  Biol.,  xlii,  1901.  565. 


THE    ABSOIU'TIOX    OF    THIO    liKDIU  Kl)    FOODSTUFFS  1029 

nesium,  cpsoiu  salt,  luul  otlicrs,  causes  largo  ciuantiticjs  of  watc^r  to  he 
poured  into  the  intestinal  canal  which  eventually  excite  peristalsis. 
Other  cathartics,  such  as  cascara  saf>;ra(la,  act  by  stinuilatinji;  the  j)eris- 
talsis  witiiout  reiulerinp;  the  feces  es]>eciall3^  watery,  and  still  others, 
such  as  the  inert,  oils,  hy  luhricating  the  intestinal  surfaces  as  well  as 
the  feces. 

While  the  experiment  just  described,  lays  special  emphasis  upon 
osmosis,  it  may  be  shown  that  this  factor  is  by  no  means  the  only 
one  concerned  in  absorption.  Thus,  it  Avill  be  remembered  that  the 
villi  of  the  small  intestine  are  supplied  with  capillaries  in  which  the 
pressure  cannot  be  less  than  30  or  40  mm.  Hg.  Evidently,  absorption 
takes  place  ajiainst  this  pressui'o.  It  has  also  been  shown  that  if  a 
certain  quantity  of  the  animal's  own  l)lood-serum  is  introduced  into 
the  intestine,  its  w^ater  and  salts  will  be  absorbed,  while  its  proteins 
are  left  behind.  Some  time  later,  however,  all  of  this  serum  is  taken 
up  and  this  in  spite  of  the  fact  that  the  fluids  on  the  two  sides  of  the 
intestinal  epithelium  are  practically  identical.  These  and  other 
experiments  that  might  still  be  mentioned,  prove  very  conclusively 
that  the  lining  cells  of  the  intestine  are  able  to  intervene  in  this  process 
by  virtue  of  certain  forces  which  originate  during  their  metabolism. 
This  impli(»s  that  the  different  substances  do  not  simply  pass  through 
the  pores  in  this  membrane,  but  actually  interact  with  the  solvent  as 
well  as  with  the  cytoplasm  of  these  cells. 

The  Absorption  of  the  Carbohydrates. — Since  only  the  mono- 
saccharides are  readily  dial,vzable,  the  polysaccharides  must  first  be 
converted  into  their  simplest  form.  We  have  seen  that  this  process 
involves  a  constant  hydrolysis  which  is  effected  by  the  enzymes 
mentioned  previousl3^  In  the  intestine,  therefore,  we  have  such 
substances  as  dextrose,  levulose  or  fructose,  and  galactose. 

The  first  is  present  in  largest  amounts  and  is  easily  diffusible  and 
reduced  by  the  tissue  cells.  Such  disacchari<les  as  cane-sugar,  milk- 
sugar,  and  maltose,  are  also  soluble  and  diffusible,  but  cannot  be  con- 
verted directly  into  glycogen,  nor  can  they  be  fully  utilized  by  the 
tissue-cells.  The  small  percentage  of  them  actually  made  available 
to  the  latter,  has  previously  been  acted  upon  by  the  maltase  of  which  a 
small  amount  is  present  in  the  bodj^-fluids.  The  difference  in  the 
diffusibilitj'  of  these  sugars  is  also  shown  by  the  fact  that  as  small 
an  amount  as  100  grm.  of  glucose  when  introduced  into  the  intestine, 
may  give  rise  to  glycosuria,  while  as  much  as  300  grm.  of  cane-sugar 
may  be  ingested  before  the  aforesaid  symptom  is  produced.  Lactose  is 
absorbed  with  even  greater  difficulty  and  hence,  this  sugar  must  pass 
into  the  feces  whenever  lactase  is  present  in  insufficient  amounts. 
The  absorption  of  the  simjjle  sugars  is  effected  chiefly  in  the  small 
intestine,  and  the  chief  channel  of  absorption  is  the  portal  vein  and 
not  the  lymphatic  system.  ^ 

1  Munk,  Archiv  fiir  Physiol.,  1890,  376. 


1030  .\BSORPTION 

The  Absorption  of  the  Fats. — In  the  upper  small  intestine  the  fats 
appear  as  glycerin  and  fatt}'  acids,  while  in  its  lower  segments 
some  of  these  fatty  acids  have  been  combined  with  alkalies  to  form 
soaps.  This  implies  that  the  neutral  fat  ingested  is  hydrolyzed  by  the 
gastric,  pancreatic  and  intestinal  juices,  the  end-products  of  this 
lipolysis  being  the  substances  just  mentioned.  We  know  that  the 
alkaline  soaps  are  soluble  in  water,  while  those  of  calcium  and  mag- 
nesium are  soluble  in  bile.  This  is  also  true  of  the  free  fatty  acids. 
Herein  really  lies  the  importance  of  bile  as  an  aid  to  pancreatic  diges- 
tion; i.e.,  while  it  does  not  dissolve  neutral  fat,  it  possesses  a  power- 
ful solvent  action  upon  fatty  acids  and  soaps  and  even  upon  the 
otherwise  insoluV^le  soaps.  From  this  statement  it  may  be  gathered 
that  this  secretion  is  a  prerequisite  of  the  normal  absorption  of  fat, 
because  in  its  absence  more  than  haK  of  this  foodstuff  is  lost  to  the 
body  and  escapes  into  the  feces.  It  cannot  surprise  us  to  find  that 
the  accumulation  of  these  masses  of  unutihzed  fat  also  seriously  in- 
terferes with  the  digestion  and  absorption  of  the  other  foodstuffs. 
Similar  conditions  result  in  the  absence  of  the  pancreatic  juice,  but 
it  seems  that  the  loss  of  this  secretion  may  be  compensated  for  in  a 
large  measure  by  the  secretions  still  remaining  as  well  as  by  the 
activity  of  micro-organisms.^ 

In  its  journey  through  the  epithelial  cells  this  material  is  then 
synthetized  into  neutral  body-fat.  The  soaps  are  spHt,  while  the  fatty 
acids  thus  liberated,  are  united  with  glycerin  to  form  neutral  fat 
under  elimination  of  water.  This  fat  is  then  diverted  into  the  lacteals 
of  the  different  villi,  whence  it  reaches  the  mesenteric  lymphatics  and 
eventually  the  thoracic  duct  and  venous  circulation.  It  is  true,  how- 
ever, that  only  about  60  per  cent,  of  the  95  per  cent,  of  the  fat  usually 
absorbed,  can  be  accounted  for  in  this  way,  whereas  the  other  40  per 
cent,  must  be  transferred  into  the  portal  radicles  directly  or  be  burned 
up  during  their  passage  through  the  intestinal  epithehum.  In  support 
of  the  former  view  might  be  mentioned  the  fact  that  from  32  to  48  per 
cent,  of  the  fat  enters  the  system  in  spite  of  the  hgation  of  the  thoracic 
duct.  Obviously,  this  absorption  can  only  take  place  through  the 
portal  terminals.  As  far  as  the  time  is  concerned  during  which  this 
transfer  is  accomphshed,  it  might  be  stated  that  in  the  dog  from  9  to 
21  per  cent,  of  the  fat  is  absorbed  within  3  to  4  hours,  21  to  46  per 
cent,  in  7  hours,  and  the  remaining  portion  in  18  hours. 

At  the  height  of  absorption  even  the  distalmost  l>Tnphatics  are 
sharply  outlined  against  the  dark  red  background  of  the  intestine 
by  their  milky  white  contents.  Even  the  blood  presents  an  oily 
appearance,  owing  to  its  admixture  with  chyle,  and  if  a  sample  of  this 
blood  is  allowed  to  clot,  the  serum  derived  therefrom  exhibits  a  white 
color,  and  fat  globules  gradually  collect  upon  its  surface.  This  cannot 
surprise  us,  because  fat  absorption  is  both  abundant  as  well  as  rapid, 

1  Leathes,  "The  Fats,"  Monographs  in  Bioch.,  Longmans,  Green  &  Co.,  1912, 
and  Dakin,  "Oxidations  and  Reductions  in  the  Animal  Body,"  ibid.,  1912. 


THE    ABSORPTION    OF    THE    REDUCED    FOODSTUFFS 


1031 


as  much  as  12  grams  of  i;it  l)cinfi;  absoibcd  Ijy  a  dog  ol"  iiiediuiu  weight 
in  the  course  of  one  hour.  Histologically,  it  is  of  interest  to  note  that 
the  fat  globules  may  be  traced  in  their  journey  through  the  epithelial 
lining  by  virtue  of  the  power  of  the  unsaturated  fatty  acids  to  reduce 
osmic  acid.  When  stained  in  this  way  they  appear  as  dark  granules 
of  varying  size  within  the  cytoplasm  of  the  different  cells.  It  should 
be  remembered,  however,  that  this  stain  does  not  furnish  a  means  of 
determining  the  actual  amount  of  fat  pres(>nt  within  these  colls,  be- 
cause only  the  free  fatt}'"  acids  are  rendered  visible  thei'eby.  On  leav- 
ing these  cells  the  fat  globules  enter  the  tributaries  of  the  lacteals.^ 
There  is  no  reason  to  believe  that  they  are  transported  into  these 
channels  by  the  leukocytes,  as  has 
been  supposed  by  Schafer  and 
others.  The  histological  picture 
just  briefly  described,  has  led  many 
observers  to  .conclude  that  the  fat 
globules  traverse  the  intestinal  epi- 
thelium in  their  original  form. 
This  view  constitutes  the  so-called 
mechanistic  theory  of  fat  absorption. 
As  we  have  seen,  the  evidence  now 
at  hand  shows  that  the  fat  is  broken 
down  and  is  reconstructed  into 
neutral  fat  before  it  leaves  the  lining 
cells.  This  fact  forms  the  basis  of 
the  chemical  theory  of  fat  absorption. 
The  Absorption  of  the  Proteins. 
— The  proteins  of  the  food  are  re- 
tained in  the  small  intestine  in  the 
form  of  peptones  and  their  amino- 
acid  derivatives.  The  latter  trav- 
erse the  intestinal  epithelium  and 
are  eventually  converted  into  the 
proteins  of  the  body.  We  know  this  to  be  true,  because  amino-acids 
may  be  isolated  from  the  blood,  and  because  animals  may  be  kept  in 
nitrogen-equilibrium  by  feeding  them  with  completely  predigested 
protein  mixtures.  It  has  also  been  observed  that  the  introduction 
of  foreign  proteins  and  even  of  peptones  into  the  circulation,  gives 
rise  to  severe  symptoms  and  may  even  result  in  the  death  of  the 
animal.  In  other  words,  the  direct  introduction  into  the  blood-stream 
of  substances  which  are  otherwise  chemically  indistinguishable  from 
the  digested  proteins  is  usually  followed  by  the  development  of  anaphy- 
lactic reactions.  These  same  substances  given  by  mouth,  are  per- 
fectly harmless.  It  appears,  therefore,  that  the  proteins  cannot  be 
absorbed  as  such  from  the  intestine,  but  must  first  be  reduced  into 

1  Whitehead,  Am.  Jour,  of  Physiol.,  xxv,   1910,   28,  and  Mendel,  ibid.,  xxir, 
1909,  493. 


Fig.  521. — Section  through  the 
Lining  Cells  of  the  Intestine  (JL\t)  at 
Different  Periods  after  the  Ingestion 
OF  Fat. 


1032  ABSORPTION 

their  amino-acids,  from  which  the  proteins  of  the  body  are  then  re- 
constructed. It  is  also  evident  that  these  products  of  protein  diges- 
tion enter  the  portal  radicles,  because  the  composition  of  the  lymph 
obtained  from  the  thoracic  duct,  is  not  appreciably  altered  during  pro- 
tein absorption.  Moreover,  it  has  been  shown  that  the  ligation  of 
this  collecting  channel  does  not  interfere  with  the  intake  of  proteins  as 
determined  by  the  output  of  urea.' 

These  facts  have  led  to  the  establishment  of  the  hypothesis  that 
the  amino-acids  are  reconstructed  into  the  proteins  of  the  blood  while 
they  traverse  the  intestinal  lining.  But  since  this  view  is  bascnl  upon 
negative  evidence,  and  is  contradicted  by  the  presence  of  amino-acids 
in  the  blood,  it  cannot  be  retained  in  its  original  form.  Instead,  it 
must  be  concluded  that  a  true  synthesis  of  the  amino-acids  by  the 
intestinal  lining  cells  does  not  take  place  and  that  these  bodies  enter 
the  blood  directly.  From  this  medium  they  are  then  picked  up  by 
the  different  cells  either  to  replace  the  protein  material  which  the  latter 
have  lost,  or  to  be  excreted  directly. ^  The  acceptance  of  this  view 
inakes  it  necessary  for  us  to  discard  the  assumption  that  the  white 
blood  corpuscles  play  a  part  in  the  transfer  of  these  bodies  from  the 
lining  cells  into  the  blood-stream  (Schafer).  Consequently,  it  may  be 
concluded  that  the  increase  in  the  number  of  leukocytes  after  meals  is 
caused  in  all  probability  by  changes  in  the  circulation. 

The  difficulties  encountered  in  endeavoring  to  prove  the  presence 
of  amino-acids  in  the  blood,  are  dependent  upon  the  fact  that  their 
absorption  is  effected  very  slowly  and  that  they  are  diluted  after  that 
by  large  quantities  of  blood,  and  carried  with  greatest  speed  to  the 
tissues.  Consequently,  they  do  not  remain  in  the  blood  for  any 
length  of  time,  but  are  quickly  acted  upon  by  the  tissue-cells.  An 
additional  difficulty  is  presented  by  the  fact  that  thcnr  chemical  isola- 
tion is  seriously  hampered  by  the  presence  in  the  blood  of  a  large  quan- 
tity of  coagulable  proteins. 

In  accordance  with  the  above  view,  the  amino-acids  must  be  re- 
garded as  mere  building  stones  which  may  be  brought  together  selec- 
tively to  form  the  botly-proteins.  This  is  also  true  of  the  amino-acids 
constituting  the  proteins  of  the  food,  because  the  differences  which  they 
show  are  really  due  to  the  manner  in  which  their  molecules  are  com- 
bined. As  soon  as  the  protein  material  has  been  split  by  the  ac- 
tion of  the  sucpessive  proteolytic  enzymes,  their  amino  constituents  are 
again  united  in  the  organism  in  accordance  with  the  peculiar  require- 
ments of  the  tissue-cells.  In  this  way,  a  large  number  of  perfectly  nev,- 
combinations  may  be  produced.  It  must  also  be  considered  a'3  an 
established  fact  that  the  intestinal  cells  possess  the  power  of  splitting 
the  amino  groups  from  those  polypeptides  which  have  been  swept 
into  them.     This  deduction  is  based  upon  the  fact  that  the  intestinal 

iFolin  and  Denig,  Jour.  Biol.  Chem.,xi,  1912,  493. 
•    ^  Paton  and  Goodall,  Jour,  of  Physiol.,  xxxiii,  1915,  20,  also  Burianand  Schur, 
Wiener,  klin.  Wochenschr.,  1897. 


THK    .\BSORPTI()N    OF    THE    HKDIXEI)    FOODSTUFFS         1033 

mucosa  contains  more  amnionic  tlian  any  other  (issue,  ami  lliat  tlie 
blood  of  the  mesenteric  veins  contains  from  G  to  10  times  as  much 
ammonia  as  that  of  other  veins. 

In  man  practically  all  the  proteins  are  taken  in  as  insoluble  com- 
pounds, or  are  rendered  so  by  the  process  of  cooking.  Their  absorp- 
tion, therefore,  necessitates  their  first  being  brought  into  solution  and 
this  end  is  attained  by  hydration  and  the  action  of  the  different  pro- 
teolytic enzymes.  Certain  evidence  is  also  at  hand  to  show  that  a 
certain  proportion  of  the  protein  may  be  absorbed  l)efor(»  it  has  ac- 
tually reached  its  final  stage  of  cleavage.  Thus,  it  has  been  mentioned 
above  that  the  proteins  of  blood-serum  are  eventually  taken  up;  in 
fact,  Friedliinder  states  that  as  much  as  21  per  cent,  of  white  of  egg 
may  be  absorbed  by  washed  small  intestine  in  the  course  of  three 
hours.  Syntonin  and  casein,  on  the  other  hand,  are  not  absorbed. 
Furthermore,  patients  fed  per  rectum  with  protein  material,  are  capa- 
ble of  absorbing  a  considerable  portion  of  it,  although  proteolytic 
enzymes  are  not  present  in  this  segment  of  the  intestine.  It  is  also  a 
matter  of  common  experience  that  certain  persons  may  tlovelop  an  idio- 
syncrasy or  anaphylaxis  against  the  proteins  of  milk  and  white  of  egg, 
which  is  due  in  all  probability  to  the  absorption  of  protein  in  its  more 
complex  form.  We  are  justified,  however,  in  concluding  that,  under 
perfectly  normal  conditions,  the  absorption  of  only  partiall}'  reduced 
protein  is  the  exception. 

Besides  the  increase  in  the  number  of  the  Icukocjiies,  it  has  been 
noted  by  Renter  that  the  cells  of  the  villi  become  swollen  when  protein 
absorption  is  going  on.  Furthermore,  their  cytoplasm  does  not  stain 
deeply  at  this  time,  owing,  in  all  probability,  to  the  accumulation  of 
a  hyaline  coagulable  material. 

B.  ABSORPTION  FROM  THE  CAVITIES  OF  THE  BODY 

Absorption  from  the  Peritoneal  Cavity. — In  the  intestine,  the  body- 
fluids  are  separated  from  the  liquefied  foodstuffs  by  a  layer  of  colum- 
nar epithelium  which  owing  to  its  depth,  is  capable  of  influencing 
diffusion  in  an  active  manner.  The  body-cavities,  on  the  other  hand, 
are  lined  with  only  a  thin  sheet  of  endothelial  cells,  and  hence,  we 
might  expect  in  this  case  a  preponderance  of  the  physical  forces. 
While  these  functional  differences  no  doubt  exist,  the  fact  still  remains 
that  the  endothelial  cells  are  by  no  means  perfectl}^  passive  entities. 
We  have  really  come  to  this  conclusion  on  previous  occasions,  while 
discussing  the  part  played  by  the  glomerulus  in  the  formation  of  urine 
and  the  function  of  the  endothehum  of  the  blood  capillaries  in  the  pro- 
duction of  lymph.  As  far  as  the  lining  of  the  pleural  and  peritoneal 
cavities  is  concerned,  it  has  been  noted  repeatedly  that  pleural  and 
ascitic  effusions  may  be  reabsorbed  in  the  course  of  time,  provided 
the  cause  leading  to  these  extravasations  has  ceased  being  active. 


1034  ABSORPTION 

This  is  also  true  of  blood-serum  and  isotonic  salt  solutions  when  intro- 
duced into  these  spaces. 

In  general,  it  maj'be  said  that  the  endothelium  acts  in  the  same  man- 
ner as  other  animal  membranes.  Thus,  it  has  been  shown  by  Roth^ 
that  the  introduction  of  hypotonic  salt  solutions  into  the  peritoneal 
cavity  leads  to  a  rapid  absorption  of  its  water  until  it  has  become  isos- 
motic  with  the  blood.  Eventually,  all  of  the  solution  disappears  from 
this  cavity.  A  hypertonic  salt  solution,  on  the  other  hand,  first  draws 
water  from  the  blood  until  an  isosmotic  condition  has  been  established. 
The  fluid  as  a  whole  then  begins  to  pass  over  into  the  system.  It  is 
difficult  to  explain  these  phenomena  unless  we  assume  with  Reckling- 
hausen- that  the  peritoneal  cavity  stands  in  direct  communication 
with  the  lymphatic  sj^stem  by  means  of  minute  defects  or  stomata 
which  are  situated  between  the  individual  endothelial  plates.  Thus, 
while  the  ordinary  laws  of  diffusion  would  play  the  most  important 
part  to  begin  with,  the  final  escape  of  the  fluid  would  occur  through 
these  openings.  This  explanation  has  much  in  its  favor  and  especi- 
ally since  this  absorption  is  proportional  to  the  pressure  under  which 
the  fluid  is  injected  into  the  cavity.  But  inasmuch  as  the  aforesaid 
stomata  have  not  been  definitely  recognized  by  histologists,  Starling^ 
has  supposed  that  the  absorption  from  these  cavities  is  dependent  upon 
the  fact  that  the  proteins  of  the  blood  are  indiffusible  and  exert,  there- 
fore, a  considerable  osmotic  pressure  upon  the  neighboring  salt  solu- 
tion. This  explanation  is  strengthened  by  the  fact  that  the  absorbed 
material  enters  the  blood  and  not  the  lymph,  because  the  ligation 
of  the  thoracic  duct  does  not  impede  this  process.  Obviously,  this 
subject  is  still  in  a  decidedly  theoretical  state  and  we  cannot  do  much 
else  at  the  present  time  than  to  consider  it  in  the  same  hght  as  the  for- 
mation of  the  hnnph,  i.e.,  we  must  suppose,  and  rightly  so,  that  the 
purely  physical  factors  of  diffusion  and  osmosis  are  modified  by  the 
metabolic  activity  of  the  endothelial  cells. 

Absorption  Through  the  Skin. — It  has  been  stated  in  one  of  the 
preceding  chapters  that  the  skin  excretes  carbon  dioxid,  water,  salts 
and  at  times  also  urea.'*  To  what  extent  the  skin  may  also  be  regarded 
as  an  organ  of  absorption  has  not  been  definiteh"  ascertained,  although 
it  may  be  assumed  that  this  function  must  differ  in  different  animals. 
Concerning  the  skin  of  man  it  has  been  established  that  it  possesses 
practically  no  absorbing  power  under  ordinarj^  conditions,  whereas 
that  of  the  frogs  and  eels  (not  the  fish)  absorbs  oxygen  as  well  as  water, 
alcohol,  and  possibly  also  salts  and  other  substances.' 

1  Engelmann's  Archiv.,  1899. 

2  Virchow's  Archiv,  xxvi,  72;  also:  Meltzer,  Jour,  of  Physiol.,  xxii,  1898,  196. 

3  Jour,  of  Physiol.,  x\nii,  1895,  106. 

^  Schierbeck,  Archiv  fiir  Physiol.,  1893,  and  Taylor.  Jour.  Biol.  Chem.,  ix,  1911, 
21. 

5  Berg,  Dissertation,  Dorpat,  1868,  Bohr.  Skand.  Archiv  fiir  Physiol.,  x,  1900, 
88,  and  Maxwell,  Am.  Jour,  of  Physiol.,  xxxii,  1913,  286. 


THE    ABSORPTION    OF   THE    REOTTrED    FOODSTUFFS         1035 

C.  THE  FORMATION  OF  THE  FECES 

Character  of  the  Feces. — The  iwvs  juv  alkaline  in  their  reaction, 
and  contain  the  intli<>;estil)le  constituents  of  the  f(;o(l  plus  a  very  snuill 
proportion  of  nutritive  material  which  has  escaped  digestion,  epithelial 
cells,  pigment,  mucin,  and  countless  bacteria.  The  products  of  bac- 
terial decomposition,  include  indol  and  scatol  to  which  their  disagree- 
able odor  is  due,  and  also  ('(Miain  gases,  such  as  NH4,  C'02,  H,  Nand 
H2S.  A  small  quantity  of  f(>cal  material  is  also  excreted  during 
periods  of  starvation,  as  well  as  from  isolated  loops  of  intestine.  In  the 
latter  case,  however,  it  consists  solely  of  desquamated  epithelium, 
intestinal  juice,  and  bacteria;  simulating,  therefore,  the  meconium  of 
the  new-born  child  which  embraces  solely  concentrated  bile  and  cast- 
off  epithelium.  The  character  of  the  feces  of  a  normal  adult  depends 
in  a  large  measure  iipon  the  type  of  the  food  ingested.  They  contain 
elastic  fibers,  and  the  remnants  of  the  connective  tissues,  spiral  ves- 
sels of  plants,  and  vegetable  residue  in  the  form  of  cellulose.  When 
no  vegetables  have  been  ingested,  about  60  to  75  per  cent,  of  the  feces 
consist  of  water,  while  their  dry  residue  contains  about  7  per  cent,  of 
nitrogenous  material.  Their  non-nitrogenous  portion  is  composed 
of  about  11  to  12  per  cent,  of  ash  and  12  to  18  per  cent,  of  substances 
soluble  in  ether,  as  well  as  of  sterobilin  and  other  bile  residues.  The 
ethereal  extract  embraces  fatty  acids,  cholesterol,  a  small  amount 
of  lecithin,  and  neutral  fat.  The  proteins  consist  of  mucin  and  nucleo- 
protein,  derived  from  the  epithelial  cells  and  the  countless  numbers  of 
bacteria.  The  ash  embodies  chiefly  calcium  phosphate  and  small 
amounts  of  iron  and  magnesium. 

Very  different  conditions  are  met  with  if  the  diet  contains  large 
amounts  of  cellulose,  because  this  material  escapes  from  the  small 
intestine  unchanged  and  may  carry  other  substances  with  it.  In 
the  large  intestine,  it  is  first  acted  upon  in  a  slight  measure  by  bacteria 
before  it  actually  becomes  a  constituent  of  the  feces.  Thus,  Voit  has 
shown  that  as  much  as  42  per  cent,  of  the  nitrogen  of  the  food  of  vege- 
tarians may  be  lost  to  the  system,  obviously  because  the  digestive 
juices  cannot  penetrate  its  cellulose  investments.  Only  about  85  per 
cent,  of  the  dry  substance  of  green  vegetables  is  available  for  absorp- 
tion, and  only  80  per  cent,  of  carrots  and  turnips.  But  naturally,  the 
vegetable  proteins  as  such  are  as  digestible  as  the  animal  proteins, 
and  their  complete  utilization  requires  merely  maceration  and  cooking 
to  free  them  from  the  cellulose.  In  the  herbivora,  of  course,  condi- 
tions are  quite  different,  because  in  them  the  beginning  portion  of  the 
large  intestine  is  set  aside  especially  for  the  digestion  by  fermentation 
of  these  particular  types  of  foods.  This  material  may  remain  here 
for  two  or  three  days,  while  it  undergoes  slow  reduction  and  absorption. 

Botulism. — Excessive  protein  putrefaction  in  the  intestine  may 
give  rise  to  a  complex  of  symptoms,  consisting  of  constipation,  vertigo, 
diplopia,  hemianopia,  difficulty  in  swallowing,  weakness,  and  cardiac 


1036  ABSORPTION 

irregularities.  In  most  instances,  tliese  symptoms  are  attributable  to 
an  unusual  inactivity  on  the  part  of  the  large  intestine  or  to  the 
ingestion  of  smoked  and  canned  meat  and  other  foods.  It  is  said 
that  these  toxins  are  derived  from  processes  instigated  by  the  Bacillus 
hotulinus,  an  anaerobe  which  is  easily  destroyed  by  the  cooking  of  the 
food. 

The  Formation  of  the  Feces. — Even  at  the  height  of  digestion  the 
small  intestine  is  not  distended  with  food,  but  contains  merely  froth 
and  semi-solid  masses  of  mucous  material  which  are  never  large  enough 
to  separate  its  walls  very  widely.  Hence,  the  name  of  jejunum  or 
"empty  gut."  This  peculiar  condition  finds  its  oi'igin  in  the  periodic 
entrance  of  chyme  and  its  relatively  rapid  distribution  through  a  large 
stretch  of  intestine.  At  the  ileocecal  valve  a  certain  quantity  of  its 
water  has  already  been  abstracted  from  this  material,  although  enough 
of  it  is  left  behind  to  give  to  the  contents  of  the  cecum  the  consistency 
of  a  thick  broth.  The  regular  and  antiperistaltic  movements  of  this 
segment,  together  with  those  of  the  ascending  colon,  then  allow  suffi- 
cient time  for  most  of  this  water  to  be  absorbed,  so  that  the  transverse 
colon  receives  this  material  in  a  more  compact  and  dry  form.  Ob- 
viously, any  retardation  of  the  feces  must  tend  to  increase  this 
absorption  of  water,  permitting  them  to  become  more  firmly  lodged 
in  the  haustral  spaces,  whence  they  are  dislodged  only  with  difficulty. 
In  extreme  cases  of  constipation  even  the  descending  colon  may  be- 
come blocked  with  these  impacted  masses,  which  then  set  up  disturb- 
ing reflexes  by  virtue  of  their  irritating  action  upon  the  intestinal 
mucosa  and  neighboring  abdominal  organs. 

While  it  is  not  my  intention  to  enter  into  a  lengthy  discussion  of 
the  causes  and  effects  of  intestinal  stasis  and  constipation,  it  might  be 
mentioned  that  the  ingestion  of  food  containing  a  larger  proportion 
of  vegetables  may  obviate  this  difficulty,  because  it  tends  to  shorten 
the  time  consumed  in  the  passage  of  the  food  through  the  intestine. 
This  result  it  accomplishes  first  by  virtue  of  its  greater  content  in* 
water,  and  secondly,  by  means  of  its  stimulating  influence  upon  peri- 
stalsis. Consequently,  the  indigestible  cellulose  of  the  food  is  not  with- 
out value,  because  it  increases  the  bulk  of  the  feces  and  sets  up  certain 
mechanical  reactions,  which  lead  to  a  quicker  evacuation  of  the  large 
intestine.  This  point  is  more  fully  illustrated  by  the  fact  that  an 
ordinary  mixed  diet  gives  rise  to  a  daily  output  of  feces  consisting  of 
about  100  gnn.  of  water  and  35  grm.  of  solids,  whereas  a  vegetable 
diet  yields  260  grm.  of  water  and  75  grm.  of  solids. 


HISTORY    OF   DIFFERENT    FOODSTUFFS    IN   BODY  1037 


C'HAPTER  LXXXVT 

THE  HISTORY  OF  THE  DIFFERENT  FOODSTUFFS 
IN  THE  BODY 

General  Discussion. — The  process  of  alimentation  having  been 
completed  by  the  absorption  of  the  foodstuffs,  the  latter  circulate  in 
the  blood  and  are  then  acted  upon  by  the  cells  of  the  different  tissues. 
One  of  two  things  may  now  happen  to  them,  namely,  they  may  be 
taken  up  to  form  an  intricate  part  of  the  tissue-substance  or  may  be 
burned  up  immediately  and  excreted.  Eventually,  of  course,  even 
the  first  portion  must  again  be  discharged  by  the  cells  into  the  cir- 
culating media,  because  activity  entails  a  constant  loss  of  substance. 
As  far  as  excretion  is  concerned,  it  is,  therefore,  quite  immaterial 
whether  a  given  foodstuff  first  becomes  an  actual  part  of  a  cell  or  does 
not,  because  both  portions  are  finally  turned  into  waste  products. 
Clearly,  every  living  entity  attains  at  a  particular  time  of  its  life  a 
mature  size  which  it  retains  for  some  time  by  properly  balancing  its 
outgo  in  waste  material  by  an  adequate  ingo  of  nutritive  substances. 
Meanwhile  its  physiological  destiny  is  to  produce  energy  in  its  various 
forms,  simulating  a  steam  engine  which  converts  its  fuel  into  waste 
under  an  evolution  of  energy.  In  order  to  satisfy  its  wants;  to  retain 
its  weight;  and  to  enable  it  to  yield  energy,  the  living  substance  re- 
quires fresh  air,  drink  and  food.  Only  when  each  of  these  three 
things  is  supplied  to  it  can  it  continue  incessantly  to  oxidize  and  to 
produce  work.  Thus,  each  cell  may  be  said  to  be  in  a  state  of  un- 
stable equilibrium  which  favors  the  building  up  processes  during  its 
period  of  growth  and  the  tearing  down  processes  during  its  period 
of  decline. 

While  cellular  anabolism  and  catabolism  in  this  general  form  is 
not  difficult  to  understand,  it  is  true  that  we  are  not  as  yet  in  a  satis- 
factory position  to  follow  the  different  foodstuffs  in  their  journey 
through  the  body  with  exactness.  The  reason  for  this  lies  in  the 
extreme  complexity  and  invisibility  of  the  intracellular  processes. 
Regarded  in  a  general  way,  it  may  be  said  that  the  body  consists  of 
64  per  cent,  of  water,  16  per  cent,  of  proteins,  14  per  cent,  of  fat,  5  per 
cent,  of  salt,  and  1  per  cent,  of  carbohydrates.  Among  its  constituents 
might  be  mentioned  carbon,  nitrogen,  hydrogen,  oxygen,  sulphur,  phos- 
phorus, fluorin,  chlorin,  iodin,  sodium,  potassium,  calcium,  silicon, 
magnesium,  lithium,  iron,  and  at  times  also  traces  of  manganese,  copper 
and  lead.     Excepting  oxygen,  nitrogen  and  hydrogen,  these  elements 


1038  ABSORPTION 

are  usually  united  into  compounds,  forming  (a)  the  mineral  or  inorganic 
constituents,  and  (b)  the  organic  constituents  of  our  body.  Physiolog- 
ical chemistry  concerns  itself  chiefly  with  the  latter  which  present 
themselves  as  carbohydrates,  fats  and  proteins.  So  far,  however, 
chemical  analyses  have  not  succeeded  in  establishing  anything  further 
regarding  the  ''life  history"  of  these  substances  than  what  might  be 
termed  a  balance  sheet  between  their  ingo  and  outgo.  This  need  not 
surprise  us,  because  even  the  simplest  determinations  frequently 
necessitate  difficult  analytical  procedures.  In  general,  it  may  be  said 
that  our  knowledge  regarding  the  sum  total  of  the  changes  which  the 
foodstuffs  undergo  in  our  body  (metabohsm)  has  been  derived  from 
determinations  of: 

(a)  the  quantity  and  quality  of  food  ingested, 

(&)  the  quantity  and  quality  of  the  material  excreted, 

(c)  the  weight  of  the  animal  before  and  after  the  experiment,  and 

(d)  the  energy  evolved  by  the  animal  in  the  form  of  work  and  heat, 
while  in  the  calorimeter. 


THE  METABOLISM  OF  THE  CARBOHYDRATES 

The  Formation  of  Glycogen. — The  animal  derives  its  carbohydrates 
in  the  main  from  vegetable  carbohydrates  which  upon  digestion 
yield  three  monosaccharides,  namely,  glucose,  fructose  and  galactose. 
About  500  grm.  of  carbohydrate  are  ordinarily  ingested  in  the  course 
of  a  day.  Our  body,  however,  is  normally  unable  to  synthetize  this 
foodstuff,  differing  in  this  regard  very  sharply  from  the  plants,  which 
are  able  with  the  help  of  the  chlorophyll  to  form  a  simple  carbo- 
hydrate, probably  formic  aldehyde,  from  carbon  dioxid  and  water. 
By  condensation  this  simple  substance  is  then  changed  into  sugar,  and 
eventually  into  starch.  Since  the  aforesaid  sugars  are  easily  inter- 
convertible, the  tissues  may  form  whatever  type  of  sugar  they  need. 
This  is  true,  for  example,  of  lactose,  a  constituent  of  the  secretion  of 
the  mammary  glands,  and  of  the  galactosides  of  nervous  tissue.  Since 
lactose  is  a  compound  of  glucose  and  galactose,  it  requires  only  a  very 
slight  intermolecular  rearrangement  to  produce  this  substance.  In 
other  words,  there  is  sufficient  evidence  at  hand  to  show  that  one  type 
of  sugar  may  be  transformed  into  another  either  by  the  cells  of  all 
the  tissues  or  only  by  those  of  certain  tissues. 

It  has  been  ascertained  by  CI.  Bernard  (1853)  that  the  sugar  ab- 
sorbed is  not  passed  directly  into  the  circulation,  because  the  amount 
of  reducing  sugar  present  in  the  blood  retains  the  almost  constant 
value  of  0.1  to  0.15  per  cent,  even  at  the  height  of  digestion.  In 
between  the  successive  periods  of  absorption  the  percentage  of  this 
substance  in  the  blood  of  the  portal  vein  is  about  the  same  as  that  of 
the  blood  in  the  systemic  channels,  whereas  during  absorption  the 


HISTORY    Ol'    DIFFKHKNT    FOODSTUFFS    IN   BODY  1030 

sugar-content  of  the  former  is  markedly  raised,'  Those;  facts  hnmo- 
diately  suggest  that  some  barrier  is  interposed  which  prc^ventstho  newly 
ahs()rl)(>d  sugar  from  eiilering  (h(>  general  circulation.  This  coiielusion 
is  also  upheld  hv  tlu;  fact  that  exti-acts  of  the  livers  of  animals  which 
had  been  killed  some  time  beforehand,  contained  a  large  (juantity  of 
reducing  sugar,  while  those  of  washed  livers  exhibited  an  opalescence 
which  was  proved  to  be  caused  by  the  pr(\sence  of  a  polysaccharide, 
known  as  qhicogcn  (Cf.HioOnn)-  When  an  extract  of  this  kind  is  treated 
with  alcohol,  it  yields  an  abundant  precipitate  which  may  be  con- 
verted into  sugar  by  hydrolysis  with  a  mineral  acid.  This  conversion 
also  takes  place  in  pieces  of  liver  which  have  been  allowed  to  stand  for 
some  time,  so  that  their  yield  of  glycogen  gradually  becomes  less, 
while  their  content  in  glucose  increases.  In  either  case,  this  glyco- 
genolyms  proves  that  the  hepatic  cells  must  contain  some  enzyme 
which  is  capable  of  effecting  this  transformation.  The  name  of 
glycogenase  has  been  applied  to  it. 

After  an  abundant  intake  of  carbohydrates  glycogen  may  be 
present  in  the  liver  in  as  large  amounts  as  12  per  cent,  of  the  weight 
of  the  fresh  organ.  It  is  demonstrable  here  in  the  form  of  hyalin 
chips  which  give  a  characteristic  port-wine  color  with  iodin;  more- 
over, a  liver  of  this  kind  is  large,  soft  and  easily  injured.  But  while 
the  chief  source  of  glycogen  is  the  assimilable  carbohydrate  material 
of  the  food,  namely,  glucose,  fructose,  galactose  and  mannose,  it  may 
also  be  formed  from  proteins  or  the  products  of  their  decomposition. 
Whether  this  conversion  takes  place  under  normal  conditions  cannot 
be  stated  with  certainty,  altholigh  it  is  known  that  a  starving  animal 
may  employ  this  means  to  retain  a  certain  store  of  sugar.  Thus, 
it  will  be  found  that  the  liver  of  an  animal  during  starvation  contains 
only  a  very  small  amount  of  glycogen,  whereas  its  blood  sugar,  al- 
though less  than  normal,  has  not  disappeared  altogether.  This  rem- 
nant of  liver-glycogen,  however,  may  be  removed  without  difficulty 
by  supplementing  the  starvation  with  muscular  work.  Inasmuch  as 
no  carbohydrates  are  ingested  during  this  period,  and  inasmuch  as 
the  glycogen  of  the  liver  and  muscles  has  been  used  up,  it  is  evident 
that  some  sugar,  or  a  substance  similar  to  it,  must  have  been  formed 
from  the  proteins.  This  deduction  seems  justified,  because  no  evi- 
dence has  been  presented  as  yet  to  show  that  glycogen  may  also  be 
derived  from  the  fats.  Further,  if  an  animal  whose  store  in  glycogen 
has  been  exhausted,  is  fed  with  washed  fibrin,  caseinogen,  or  even 
amino-acids,  the  liver  will  be  found  to  have  acquired  glycogen.  This 
substance  also  quickly  disappears  if  the  starving  animal  is  thrown  into 
convulsions  by  means  of  strychnin.  If  these  spasms  are  stopped 
later  on  by  the  administration  of  chloral,  a  certain  amount  of  glycogen 
is  again  found  in  the  liver,  derived  in  all  probability  from  the  tissue 
proteins. 

1  McLeoud  and  Fulk,  Am.  Jour,  of  Physiol.,  xlii,  1917,  193,  and  Dakin,  Oxida- 
tion and  reduction  in  the  animal  body,  Monogr.  in  Biochem.,  1912. 


1040  ABSORPTION 

Our  search  for  the  possible  source  of  this  glycogen  leads  us  first 
of  all  to  mucin,  which  j-ields  a  considerable  amount  of  carbohydrate, 
but  this  substance  does  not  play  a  significant  part  in  metabolism. 
Contrariwise,  it  has  been  proved  that  casein,  which  does  not  contain  a 
carbohydrate  radicle,  may  be  made  to  j-ield  sugar  when  fed  to  animals 
suffering  from  phloridzin  glycosuria.  Similar  tests  with  different 
amino-acids  have  given  positive  and  negative  results,  although  their 
composition  does  not  vary  very  considerably.  Two  of  these,  however, 
have  been  proved  to  yield  sugar,  namely,  alamin  and  aspartic  acid. 
In  the  former  instance  this  conversion  is  not  difficult  chemically,  be- 
cause the  substitution  of  HO  in  its  molecule  for  XHo  gives  lactic  acid, 
from  which  sugar  may  be  obtained  without  much  difficulty.  Quite 
similarly,  if  aspartic  acid  loses  carbon  dioxid,  it  is  transformed  into 
lactic  acid.  Another  substance,  the  conversion  of  which  into  carbo- 
hydrate does  not  seem  improbable,  is  glycerol.  It  may  be  concluded, 
therefore,  that  the  body  possesses  the  power  of  forming  its  sugar  from 
the  aforesaid  substances,  and  possibly  also  from  other  amino-acids, 
although  the  chemistrj^  of  their  conversion  is  not  so  obvious  as  in 
the  cases  just  cited.  Under  ordinary'  circumstances,  however,  the 
body  derives  its  glycogen  directly  from  the  carbohydrates  of  the  food. 

The  Utilization  of  Sugar. — In  the  ceUs  of  the  liver  a  twofold 
process  is  going  on.  namely,  a  conversion  of  the  sugar  into  glycogen, 
and  a  reconversion  of  this  polysaccharide  into  circulating  sugar  under 
the  influence  of  an  enz^^Tne.  We  have  seen  that  this  circulating  sugar 
is  changed  in  the  pancreas  into  a  form  (colloid)  which  is  more  acceptable 
to  the  tissue  cells,  i.e.,  one  which  they  can  burn  up  more  readily  than 
ordinary-  glucose.  Consequently,  the  glycogen  of  the  liver  ser^^es  as 
a  reserve  material  which  is  deposited  here  temporarily  as  an  inert 
polysaccharide.  But  the  liver  is  not  the  only  storehouse  of  sugar, 
because  it  is  also  found  in  abundant  amounts  in  the  muscle  tissue. 
The  difference  between  these  two  stores  seems  to  be  one  of  availabiHty, 
because  if  a  muscle  is  suddenly  called  upon  to  do  extra  work,  it  cannot 
await  the  transfer  of  sugar  from  the  liver.  It  is  for  this  reason  that 
rapidly  growing  tissues  invariably  contain  much  glycogen  which  they 
make  use  of  in  the  course  of  their  subsequent  development.  Thus, 
while  sugar  is  normally  released  by  the  liver  into  the  blood  stream, 
the  outlying  depots  are  there  for  the  purpose  of  serving  the  more  im- 
mediate needs  of  the  body. 

It  is  a  weU-known  fact  that  even*-  contraction  of  muscle,  whether 
in  the  body  or  outside  of  it,  consumes  glucose.  Thus,  the  normally 
contracting  heart  necessitates  about  4  mgr.  of  this  substance  per  gram 
of  tissue  in  the  course  of  1  hoiu*.^  Now,  since  the  muscle  tissue 
forms  about  42  per  cent,  of  the  body  weight,  its  requirements  in  sugar 
must  be  considerable.  Moreover,  since  our  body  contains  only  1.0 
per  cent,  of  carbohydrates,  it  will  be  seen  that  this  foodstuff,  contrary'' 

^  Starling  and  Knowlton,  Jour,  of  Physiol.,  xlv,  1912,  146. 


HISTORY    OF    DIFFERENT    FOODSTUFFS    IX    BODY  1041 

to  the  proteins,  does  not  serve  as  a  permanent  building  stone,  but 
merely  as  a  temporary  acquisition  which  is  destined  to  yield  ener^. 

Work  and  hi'at  an^  derived  in  largest  amounts  from  the  muscles, 
and  we  have  seen  that  their  contractions  retiuire  the  presence  of  glyco- 
gen and  sugar,  and  tiiat  each  gram  of  sugar  furnishes  as  nmch  as  four 
calories  of  the  latter  form  of  energy.  Considering  the  preponderating 
mass  of  muscle-tissue  and  the  high  heat-value  of  sugar,  it  may,  therefore, 
be  concluded  that  the  oxidation  of  tliis  substance  constitutes  a  safety 
mechanism  by  means  of  which  the  body  is  enal^led  to  protect  its  real 
building  stones,  the  proteins.  Fat  plays  a  similar  role,  but  we  shall 
see  later  on  that  it  occupies  an  intermediate  position  and  serves  merely 
as  an  accessory  means  of  safeguarding  the  protein  substratum  of  the 
body.  Thus,  an  animal  may  be  retained  in  nitrogen-equilibrium  if  it 
continues  to  ingest  a  small  amount  of  protein  material  to  make  up  its 
ordinary  loss  in  tissue-proteins,  and  if  it  continues  to  take  in  a  suffi- 
cient quantity  of  carbohydrates  (or  fats)  to  make  up  for  the  energy 
requirements  of  the  body.  Inasmuch  as  the  carbohydrates  merely 
play  the  part  of  oxidizing  substances  and  sparers  of  the  tissue-proteins, 
it  will  be  seen  that  they  alone  cannot  keep  the  body  in  nitrogen- 
equilibrium.  Consequently,  an  animal  fed  exclusively  on  carbohy- 
drate food  must  eventually  lose  its  tissue-proteins,  and  starve  to  death 
in  spite  of  its  abundant  intake  of  carbohj'drates.  On  the  other  hand, 
if  an  animal  is  in  nitrogen-equihbrium  to  begin  with,  the  abundant  inges- 
tion of  carbohydrates  first  gives  rise  to  a  storage  of  glycogen  and  subse- 
quently to  a  synthesis  of  the  superfluous  sugar  into  fat.  The  latter  is 
held  in  reserve  as  an  accessory  substance  to  be  employed  for  future 
oxidations.  This  ''carbohydrate-fat"  differs  somewhat  in  its  consist- 
ency from  the  ordinary  tissue-fat. 

The  final  product  of  the  oxidation  of  sugar  is  carbon  dioxid  and 
water,  and  its  principal  excretory  channel  the  lungs.  Thus,  we  find 
that  the  increased  output  of  energy  which  accompanies  muscular 
exercise  is  characterized  by  a  greater  outgo  of  carbon  dioxid  and  a 
greater  consumption  of  oxygen.  This  respiratory  change  immediately 
suggests  an  increased  metabolism  of  the  carbohydrates  and  fats.  But, 
while  the  final  stage  of  the  oxidation  of  the  carbohydrates  is  quite  evi- 
dent, much  diversity  of  opinion  prevails  regarding  the  intermediary 
transformations  of  this  foodstuff.  The  initial  change  is  a  hydrolytic 
cleavage  which  liberates  some  chemical  energy,  and  the  final  stage  an 
oxidation  and  evolution  of  that  large  amount  of  energy,  Avhich  after 
all  is  the  purpose  of  the  reduction  of  this  foodstuff.  As  an  interme- 
diary stage  is  usually  mentioned  the  production  of  lactic  acid,  through 
the  preliminary^  formation  of  glyceric  aldehyde  and  methjdglyoxal. 
It  has  been  shown  that  lactic  acid  is  present  in  the  body  chiefly  as  the 
dextro-rotatory  variety  or  sarcolactic  acid,  and  as  the  optically  inactive 
variety.  Whether  all  of  this  lactic  acid  is  derived  from  the  sugars  is 
still  in  doubt,  although  it  must  be  admitted  that  this  is  its  principal 
source. 

66 


1042  ABSORPTION 

The  Regulation  of  the  Sugar  Supply  of  the  Body. — The  sugar  con- 
tent of  the  blood  of  the  general  circulatory  system  is  determined  by 
two  factors,  namely,  by  the  production  of  glucose  by  the  liver  (glyco- 
genolysis),  and  by  the  consumption  of  this  substance  by  the  tissues 
(glycolj^sis) .  Both  these  processes  are  in  turn  dependent  upon  an 
adequate  conversion  of  the  absorbed  sugar  into  glycogen  (glycogenesis). 
Consequently,  it  ma}^  be  said  that  the  sugar  content  of  the  body  is 
the  result  of  an  interaction  between  these  three  factors,  and  that  such 
conditions  as  hyperglycemia  and  glycosuria  are  the  outcome  of  a  dis- 
turbance in  any  one  or  several  of  these  processes.^  Under  normal 
conditions,  a  harmonious  interaction  between  these  factors  may  be 
brought  about  through  the  nervous  system  or  through  chemical  agents 
contained  in  the  blood  stream.  Regarding  the  nervous  control  we 
have  the  positive  evidence  of  CI.  Bernard  that  a  puncture  of  the  floor 
of  the  fourth  ventricle  (rabbits)  is  usually  followed  by  an  excessive 
secretion  of  urine,  containing  abnormally  large  amounts  of  sugar 
(glycosuria).  This  has  led  to  the  assumption  that  the  aforesaid  ac- 
tivities are  under  the  control  of  a  special  center  which  is  often  referred 
to  as  the  glycogenic  or  diabetic  center. 

It  has  been  shown  that  the  stimulation  of  either  the  greater  splanch- 
nic nerves  or  the  hepatic  plexus  gives  rise  to  glycosuria,  the  claim 
being  made  that  these  nerves  are  concerned  with  the  storage  and  con- 
version of  glycogen  by  the  cells  of  the  liver.  It  is  held  further  that 
this  regulation  is  under  the  control  of  a  hormone  secreted  by  the 
adrenal  glands,  but  the  evidence  so  far  presented  in  support  of  this 
contention,  is  not  at  all  convincing.  In  spite  of  this  fact,  however,  it 
cannot  be  doubted  that  glycosuria  is  frequently  associated  with  mental 
excitement.  Furthermore,  the  disease  of  diabetes  mellitus  usually 
affects  persons  with  neurotic  tendencies  or  those  who  are  under  a 
constant  and  severe  mental  strain,  or  whose  work  demands  much 
mental  concentration  and  exactitude.  ^  At  present,  however,  no 
facts  are  at  hand  to  show  that  diabetes  mellitus  finds  its  initial  cause 
in  an  outpouring  of  adrenin  in  consequence  of  too  frequently  repeated 
emotions,  such  as  anger,  fear  and  fright.^ 

The  control  of  the  formation  and  consumption  of  the  sugars  by 
hormones  may  be  discussed  at  this  time  in  a  very  brief  manner,  because 
this  subject  matter  has  already  been  dealt  with  in  a  preceding  chap- 
ter. McLeod^  states  that  this  regulation  may  arise  in  consequence  of 
(a)  the  concentration  of  the  glucose  in  the  blood,  (b)  the  presence  in 
the  blood  of  the  products  of  decomposition  of  the  glucose,  and  (c)  the 
action  of  some  internal  secretion.  In  accordance  with  this  investi- 
gator, the  first  possibility  is  based  upon  the  law  of  mass  action,  in 

^  McLeod,  Physiol,  and  Biochem.  in  Modern  Medicine,  C.  Y.  Mosby,  St.  Louis, 
1918;  and  Hewlett,  Monogr.  Med.,  Appleton  and  Co.,  1917. 

^  Cannon,  Bodily  Changes  in  Pain,  Hunger,  Fear  and  Rage,  Appleton  and  Co., 
1915. 

3  Allen,  Glycosuria  and  Diabetes,  Boston,  1913;  also:  Von  Xoorden,  Metabolism 
and  Pract.  Medicine,  Chicago,  1907. 


HISTOIIV    OF    1)IFFERP]NT    F( )( )I)S  TIFFS    1  .\    IU)I)V  1043 

agreement  with  wliicli  the  coiivci-sion  of  the  glucose  into  {!;ly<''W»,  '^^ 
well  as  tlu'  coiiN-crsioii  of  the  latter  into  the  fofiner  substance,  is 
detenninecl  by  the  junounts  of  j^lucosc  in  the  blood  available  for  pur- 
poses of  oxidation.  It  eannot  be  doubted  that  this  })ro(!ess  is  actually 
at  work,  but  obviously,  the  fact  that  it  takes  plac(>  does  not  offer  an 
explanation  for  the  manner  in  which  it  is  accomplished.  The  second 
possibility  finds  its  basis  in  the  fact  that  such  products  as  lactic  acid 
and  carbon  dioxid  are  circulating  in  the  blood  and  chanp;(>  the  hydro- 
gen ion  concentration  of  the  blood,  thereby  exciting  a  gly<^ogenol3'sis. 
The  third  possibility,  that  this  regulation  is  effected  by  means  of  a  hor- 
mone sccretctl  by  some  ductless  gland,  possesses  a  sound  experimental 
basis.  Chief  among  these  internal  secretory  organs  is  the  pancreas, 
then  follow  the  adrenals,  parathyroids  and  pituitary. 

We  have  previously  noted  that  the  hyperglycemia  and  glycosuria, 
following  the  removal  of  the  pancreas,  are  due  to  the  loss  of  an  internal 
agent  which  makes  the  sugar  immediately  available  for  oxidation  by 
the  tissue  cells.  The  other  glands,  in  all  probability,  act  in  an  indirect 
way  through  the  nervous  system,  increasing  glycogenolysis.  These 
two  conditions,  therefore,  would  give  rise  to  the  so-called  pancreatic 
and  hepatic  types  of  glycosuria.  The  temporary  alimentary  type  is, 
of  course,  dependent  upon  an  increased  absorption  of  sugar  and  an 
overburdening  of  the  system  with  this  substance.  A  fourth  method  of 
producing  glycosuria  has  been  discovered  by  Mering.^  It  has  been 
used  extensively  by  Lusk,^  and  consists  in  the  administration  of  a 
glucoside,  known  as  phloridzin,  which  is  derived  from  the  bark  of  the 
roots  of  the  apple,  cherry  and  pear  trees.  It  produces  a  glycosuria 
in  spite  of  the  fact  that  the  sugar  content  of  the  blood  may  be  below 
normal.  This  shows  that  this  type  of  glycosuria  must  be  due  pri- 
marily^ to  a  leakage  of  the  sugar  through  the  kidneys  in  consequence  of 
an  injurious  action  of  this  substance  upon  the  renal  epithelium.  Phlor- 
idzin-glycosuria,  therefore,  is  a  type  of  renal  glycosuria.  The  tempo- 
rary glycosuria  which  may  be  developed  in  consequence  of  nervous 
excitement  is  in  all  probability  to  be  classified  as  a  disorder  of  glyco- 
genesis  and  glycogenolysis. 

It  will  now  be  seen  that  the  condition  of  acidosis  cannot  be  attrib- 
uted exclusively  to  a  disarrangement  of  the  carbohydrate  metabolism, 
because  the  bodies  causing  this  disturbance  are  aceto-acetic  and  j8- 
oxybutyric  acid,  which  are  the  oxidation  products  of  acetone  and  the 
fatty  acids.  When  these  substances  accumulate  in  the  course  of  dia- 
betes mellitus,  the  condition  is  known  as  ketosis.  It  appears  to  be  due 
to  the  fact  that  the  fats  cannot  be  burned  up  thoroughly  unless  their 
combustion  is  stimulated  by  the  heat  derived  from  oxidizing  sugar. 
In  the  absence  of  this  heat,  the  fats  are  imperfectly  reduced.     Conse- 

1  Verhandl.  des  Kongr.  fiir  inn.  Medizin,  vi,  1887,  and  Zeitschr.  fiir  klin. 
Med.,  1889. 

2  Zeitschr.  fiir  Biol.,  xlii,  1904,  31. 


1044  ABSORPTION 

quently,  ketosis  is  caused  by  an  imperfect  balance  between  the  metab- 
olism of  the  fats  and  carbohydrates.^ 

A  term  frequently  met  with  in  the  literature  upon  carbohj^drate 
metabolism  is  the  D :  N  ratio.  We  have  seen  that  the  absolute  with- 
drawal of  carbohydrate  from  a  diabetic  animal  does  not  prevent  the 
excretion  of  sugar  in  its  urine.  Since  this  dextrose  is  not  derived 
from  the  fats,  it  must  be  synthetized  from  the  proteins.  Minkowski 
and  Lusk^  have  shown  that  a  dog  in  complete  glucose  intolerance  may 
form  as  much  as  60  grm.  of  glucose.  Now,  inasmuch  as  100  grm. 
of  proteins  yield  about  16  grm.  of  nitrogen  in  the  urine,  the  ratio  of 
dextrose  to  nitrogen  would  be  60  :16  =  3.7.  Lusk  states  that  a  D  :N 
ratio  varying  between  3.3  and  3.7  is  a  fatal  ratio,  because  it  proves 
that  a  person  kept  on  a  diet  which  is  free  from  carbohydrate,  cannot 
consume  sugar. 

THE  METABOLISM  OF  THE  FATS 

The  Source  of  the  Body  Fat. — The  neutral  fats  formed  by  a  resyn- 
thesis  of  the  fatty  acid  and  glj'cerin  in  the  lining  cells  of  the  intestine, 
j&nd  their  way  into  the  lacteals,  whence  they  reach  the  blood  stream 
by  way  of  the  thoracic  duct.  But  since  the  fat  content  of  the  blood 
of  the  portal  vein  is  invariably  higher  than  that  of  the  external  jugular, 
it  is  claimed  by  some  investigators  that  a  slight  amount  of  fat  also 
enters  the  intestinal  capillaries  directly.  As  far  as  the  systemic  blood 
is  concerned,  it  has  been  found  that  its  content  in  fat  (0.7  per  cent.) 
remains  tolerably  constant,  provided  only  moderate  amounts  of  fat 
are  ingested.  The  intake  of  larger  quantities  of  fat,  on  the  other  hand, 
invariably  raises  its  percentage,  which  reaches  its  maximal  value  about 
6  hours  after  a  meal  and  then  gradually  declines  to  the  twelfth  hour. 
But  since  even  the  intravenous  injection  of  oil  emulsions  does  not  last- 
ingly increase  the  fat  content  of  the  blood,  it  must  be  concluded  that 
the  body  possesses  the  power  of  storing  this  fat  very  rapidty,  possibly 
in  the  liver.  Even  during  starvation  the  blood-fat  remains  rather 
constant,  proving  thereby  that  the  fat  is  being  transported  from  the 
different  depots  to  the  starving  tissues. 

In  the  animal  body  the  fats  are  usually  deposited  as  the  triglyc- 
erides of  the  different  fatty  acids,  those  of  adipose  tissue  consisting 
of  stearic,  palmitic  and  oleic  acids.  Cow's  milk  also  contains  these 
acids,  but  in  addition,  also  the  esters  of  butyric  and  caproic  acids  and 
small  amounts  of  caprylic,  capric,  lauric  and  myristic  acids.  Lard 
is  made  up  in  considerable  part  of  the  glycerides  of  the  more  unsatu- 
rated fatty  acids,  such  as  those  of  linoleic  acid.  It  is  evident,  therefore, 
that  the  composition  of  the  fat  differs  even  in  one  and  the  same  animal, 
and  may  in  addition  be  varied  by  changing  the  food.  This  fact  proves 
first  of  all  that  the  epithelial  cells  of  the  intestine  do  not  merely  resynthe- 
tize  the  glycerol  and  fatty  acids,  but  possess  the  power  of  forming  their 

^  Woodyatt,  Jour.  Am.  Med.  Assoc,  Ixvi,  1916. 
2  Science  of  Nutrition,  W.  B.  Saunders  Co.,  1912. 


HISTORY    OF    DIFFERENT    FOODSTUFFS    IN    HODV  1045 

own  particular  kind  of  chyle  fat.  Very  similar  modifications  must  also 
be  effected  by  the  tissue  cells  themselves,  becausi-  the  fats  aic  in  all 
probability  reiiych-olyzed  Iumc,  to  become  at  least  in  part  important 
constituents  of  the  protoplasm.  This  deduction  is  in  no  way  refuted 
by  the  fact  that  starving  animals,  when  fed  on  foreign  fat,  are  capable 
of  storing  this  substance  practically  unaltered.  This  merely  prov(!S 
that  it  can  be  utilizetl  in  this  form.  Thus,  Munk'  has  shown  that  an 
animal  fed  on  colza  oil,  deposits  fat  from  which  erucic  acid  may  bo 
obtained,  this  acid  being  the  basis  of  the  glyceride  contained  in  that 
oil.  In  a  similar  way,  it  has  been  demonstrated  by  Lebedeff^  that  the 
feeding  of  linseed  oil  or  mutton  fat  to  different  dogs  gives  ris(;  to  a 
deposition  of  bod}'  fat  which  is  characterized  by  a  different  melt- 
ing point;  that  derived  from  mutton  suet  remaining  solid  at  50°  C. 
Furthermore,  Liebig  has  pointed  out  that  the  fats  of  different  animals 
present  certain  peculiarities  in  their  appearance,  consistency,  inciting 
point,  and  general  chemical  properties,  and  are  in  turn  different  from 
the  fat  ordinarilj^  ingested  with  the  food.  In  fact,  many  animals,  such 
as  the  herbivora,  do  not  eat  fat,  although  they  often  acquire  a  consid- 
erable amount  of  body  fat.  But  this  is  really  an  old  established  fact, 
and  has  been  used  scientifically  by  Larves  and  G.  Wert  in  their  feeding 
experiments  upon  pigs. 

These  data  have  led  in  the  course  of  time  to  various  theories  re- 
garding the  origin  of  the  body  fat.  The  modern  view,  which  has  been 
placed  upon  a  solid  experimental  basis  by  Pfliiger,^  holds  that  it  origi- 
nates in  part  from  the  fat  and  in  part  from  the  carbohydrate  of  the  food. 
But  the  possibility  that  fat  may  also  be  derived  from  proteins,  cannot 
be  excluded,  because  since  the  latter  are  deaminized  and  converted  into 
sugar  and  glycogen,  these  products  may  in  turn  be  transformed  into 
fat.  The  proteins,  however,  cannot  form  an  important  source  of  fat 
under  ordinary  conditions,  because  they  constitute  a  relatively  small 
portion  of  the  daily  ingesta. 

While  it  cannot  be  stated  definitely  which  of  the  first  two  sources 
is  the  more  important,  the  fat  of  the  food  is  no  doubt  the  chief  element 
in  the  carnivora,  and  the  carbohydrate  in  the  herbivora.  Man,  in  all 
probability,  makes  considerable  use  of  the  carbohydrates,  because  they 
are  really  more  easily  reduced  than  the  fats.  Beyond  this  mere  fact, 
little  is  known  regarding  the  manner  in  which  this  conversion  is  ac- 
complished. It  involves,  of  course,  a  change  of  oxygen-rich  sugar 
into  oxygen-poor  fat.  Thus,  if  this  process  may  be  illustrated  with 
stearic  acid,  it  vvill  be  found  that  three  molecules  of  glucose  (CeHiaOe) 
give  stearic  acid  (C18H36O2)  under  an  evolution  of  16  atoms  of  oxygen 
The  fact  that  such  a  transformation  gives  rise  to  a  liberation  of  oxygen 
is  shown  by  animals  who  are  depositing  fat  on  carbohydrate  food. 

Their  respiratory  quotient,  ^  "  >  is  increased    considerably,    because 

^  Virchow's  Archiv,  xcv,  1884,  407. 

^  Centralbl.  fiir  die  med.  Wissensch.,  1881. 

'  Pfliiger's  Archiv,  Ixxvii,  1899,  521. 


1046  ABSORPTION 

some  of  this  oxygen  will  be  made  available  for  other  oxidations,  so  that 
the  animal  need  not  take  in  so  large  an  amount  by  respiration.  In 
addition  to  this  process  of  deoxidation,  other  changes  are  effected, 
such  as  the  reduction  of  glucose  into  two  molecules  of  lactic  acid  which 
in  turn  is  converted  into  aldehyde  and  formic  acid.  By  polymeriza- 
tion, the  aldehyde  may  then  be  changed  into  aldol  which  yields  buty- 
ric acid  on  oxidation  or  by  transposition  of  its  oxygen.^ 

The  Utilization  of  the  Fats. — The  final  product  of  the  metabolism 
of  the  fats  is  carbon  dioxid  and  water,  and  their  chief  function  to  supply 
energy.  This  being  the  case,  the  body  holds  a  considerable  portion 
of  this  substance  in  reserve  as  a  deposit  in  its  different  storehouses. 
Among  the  latter  might  be  mentioned  the  liver,  the  tissues,  and  such 
special  structures  as  the  panniculus  adiposus  in  the  deep  skin,  the  omen- 
tum, and  retroperitoneal  spaces.  Any  excess  is  stored  in  these  places 
to  be  drawn  upon  later  on  when  needed.  Thus,  fat  serves  as  an  addi- 
tional protection  to  the  proteins,  being  itself  safeguarded  by  the  carbohy- 
drates. It  presents,  however,  different  characteristics  in  accordance 
with  its  origin  and  place  of  deposition.  The  ordinary  depot-fat,  for 
example,  yields  95  per  cent,  of  its  total  weight  as  fatty  acids,  while  the 
tissue-fat  yields  only  60  per  cent.  This  might  imply  that  the  former 
is  neutral  fat,  while  the  latter  is  combined  into  lecithin  and  phos- 
pholipins.  In  the  liver,  the  character  of  the  fat  varies  with  the  inten- 
sity of  the  metabolism  of  this  organ,  being  more  like  the  fat  of  the  tissue 
during  its  periods  of  relative  quiescence  and  more  like  that  of  depot-fat 
during  its  periods  of  activity.  It  is  also  apparent  that  the  amount  of 
fat  which  may  be  stored  in  this  way  is  almost  unlimited,  contrary  to 
glycogen  which  at  best  cannot  be  stored  in  much  greater  quantities 
than  300  grm.,  i.e.,  150  grm.  in  the  liver  and  150  gnn.  in  the  muscles 
and  other  tissues. 

This  depot-fat  is  mobilized  and  transported  to  the  active  tissue 
"whenever  the  latter  has  used  up  its  own  store  of  energy-yielding 
material,  and  obviously,  this  mobilization  necessitates  its  conversion 
into  fatty  acids  and  glycerin,  which  products  again  give  rise  to  neutral 
fat  in  the  blood.  No  doubt,  the  chief  seat  of  these  oxidations  is  the 
muscle-tissue  itself,  and  principally  the  cardiac  and  skeletal  muscles. 
In  the  former,  for  example,  enough  fat  is  stored  up  to  last  for  6  or 
7  hours.  The  intake  then  being  insufficient  to  cover  the  outgo, 
all  the  available  stored  fat  is  drawn  upon.  Thus,  a  starving  animal 
first  exhausts  its  relatively  small  store  of  glycogen  and  then  its  depot- 
fat  to  the  extent  of  90  per  cent,  of  the  energy  required.  Consequently, 
a  fat  animal  is  able  to  survive  complete  abstinence  from  food  much 
longer  than  a  lean  one.  Besides  this  important  function  as  a  source 
of  energy,  the  body-fat  also  serves  as  a  factor  in  regulating  the  body- 
temperature  by  preventing  an  undue  heat-dissipation,  and  lastly,  as  a 
factor  in  protecting  delicate  structures  from  mechanical  injury. 

The  question  whether  the  liver  possesses  a  special  influence  upon 
^Leathes,  The  Fats,  Monogr.  in  Bioch.,  Longmans,  Green  and  Co.,  1912. 


HISTOin     OF    DIKFKIIEXT    I'OODSTII- FS    I\    1U)I)Y  1047 

the  metabolism  of  the  fats,  cannot  ho  deciflod  at  this  time.  It  iscvidcrit 
that  this  oif^an  may  absorb  a  considerable  pioportion  of  its  fat.  directly 
from  the  portal  blood.  Thus,  Ilaper'  has  shown  that  as  much  as  30 
per  cent,  of  cocoanut  introduced  in  thi;  intestine,  may  be  recovered 
from  the  liver.  The  same  is  true  of  unsaturated  oils,  such  as  cod-liver 
oil  and  other  fish  oils.  This  probably  accounts  for  tiieir  greater  nutri- 
tive value.  In  adcHtion,  it  has  been  shown  that  th<'  liver  possesses 
the  power  of  desaturatin^  fat,  whicli  may  render  it  more  easily  reduci- 
ble than  saturated  fatty  acid.  But,  inasmuch  as  this  organ  also  aids  in 
synthetizing  fatty  acid  radicles  into  the  complex  molecule  of  lecithin, 
it  is  entirely  jirobable  that  this  desaturation  constitutes  a  preliminary 
step  in  this  process  of  buikhng  up  lecithin.  While  this  substance  is 
made  up  of  gylcerin,  fatty  acids,  glyceryl-phosphoric  acid,  and  a  nitrog- 
enous base  cholin,  it  also  seems  to  contain  admixtures  of  proteins  or 
carbohydrates. 

Fatty  Degeneration.  Obesity. — Under  abnormal  conditions,  the 
cells  of  such  organs  as  the  liver,  heart,  and  kidneys  may  undergo 
degenerative  changes  which  make  them  appear  as  if  filled  with  ex- 
tremely fine  globules  of  fat.  This  is  a  common  result  of  poisoning  with 
phosphorus,  arsenic  or  antimon3\  Although  formerly  believed  to  be 
due  to  a  conversion  of  the  proteins  of  the  cytoplasm  into  a  fat-like 
substance,  fatty  degeneration  is  now  known  to  be  caused  either  by 
an  infiltration  of  the  cells  with  fat  transported  from  elsewhere  or  by  a 
transformation  of  the  molecular  fat  of  the  cells  into  a  different  variety 
of  it.  For  this  reason,  it  cannot  be  said  that  a  fatty  degenerated  cell 
contains  a  greater  amount  of  fat  than  it  did  normally;  in  fact,  in 
many  instances  the  reverse  relationship  holds  true.  Lusk,  however,  has 
shown  that  these  poisons  also  interfere  with  the  metabolism  of  the 
proteins  in  an  indirect  way  by  favoring  the  conversion  of  the  carbohy- 
drate-like radicle  of  the  proteins  into  leucine  and  tyrosine,  necessitat- 
ing for  this  reason  an  increased  consumption  of  protein. 

Obesity  signifies  a  disproportion  betw^een  the  total  mass  of  the 
body  and  that  made  up  of  fat.  This  condition  is  caused  by  an  exces- 
sive deposition  of  fat  within  the  different  depots  of  the  body,  giving 
rise  to  changes  in  the  contours  of  the  latter  and  various  interferences 
with  its  normal  activities  and  movements.  In  many  instances, 
however,  it  is  difficult  to  say  just  where  the  abnormal  begins,  because 
animals  differ  very  greatly  in  their  fat-carrying  capacity.  It  is 
evident  that  the  great  majority  of  animals  may  be  made  to  lay  on 
fat  by  lessening  their  expenditure  of  energy  or  by  increasing  their 
intake  of  carbohydrates  and  fats.  Since  this  is  a  perfectly  physiolog- 
ical phenomenon,  the  only  condition  to  explain  is  the  excessive  deposi- 
tion of  fat  on  a  normal  or  reduced  diet  in  the  presence  of  a  normal  or 
even  increased  expenditure  of  energy.  It  has  previously  been  pointed 
out  that  the  metabolism  of  the  fats  may  be  dependent  in  some  measure 
upon  the  secretion  of  some  ductless  gland.     In  the  absence  of  this  in- 

1  Jour.  Biol.  Chem.,  xiv,  1913,  117. 


1048  ABSORPTION 

ternal  agent,  the  oxidation  power  of  the  tissues  is  interfered  with, 
thereby  causing  an  excessive  storage  of  this  material.  Secondly, 
obesity  may  be  due-  to  an  unusually  high  efficiency  of  those  organs 
which  are  directly  concerned  with  fat  metabolism,  enabling  them  to 
keep  the  body  as  a  whole  in  a  proper  condition  on  an  unusually  low 
supply  of  food.  Obviously,  this  condition  can  only  be  remedied  by 
a  lessened  ingestion  of  food  and  a  greater  expenditure  of  energy. 
The  latter  alone  can  do  no  good,  because  if  the  patient  is  then  allowed 
to  control  his  intake  in  accordance  with  his  appetite,  he  no  doubt  would 
endeavor  to  balance  the  greater  outgo  by  a  greater  intake.  It  should 
be  remembered,  however,  that  a  fat  person  actually  needs  a  slightly 
greater  production  of  energy  than  a  lean  person,  because  his  body  sur- 
face is  larger,  favoring  heat  dissipation. 

THE  METABOLISM  OF  THE  PROTEINS 

The  Source  of  the  Protein  of  the  Body. — It  will  be  remembered 
that  the  proteins  of  the  food  are  completely  hydrolyzed  into  their 
amino-acids,  and  are  absorbed  as  such  and  passed  into  the  portal 
blood  stream.  Under  ordinary  conditions,  the  only  slightly  hydro- 
lyzed products  of  protein  digestion,  such  as  peptone  and  proteose, 
are  not  absorbed  in  significant  amounts,  because  it  is  a  well-known  fact 
that  these  substances,  when  injected  directly  into  the  blood  stream, 
produce  symptoms  of  intoxication.  This  anaphylaxis,  however,  does 
not  follow  if  they  are  introduced  into  the  intestinal  canal.  Whatever 
proportion  of  them  may  find  its  way  into  the  epithelial  lining  cells 
must,  therefore,  be  reduced  and  changed  in  its  course  through  these 
cells  into  inert  proteins.  This  change  may  also  be  effected  while  they 
circulate,  because  their  concentration  in  the  blood  can  never  be  in- 
creased sufficiently  to  produce  injurious  effects.  Such  a  result  is 
prevented  ordinarily,  because  they  are  brought  into  contact  with  a 
very  large  quantity  of  blood,  and  because  the  quantity  of  the  still  un- 
reduced protein  within  the  intestine  is  very  small.  At  all  events,  the 
evidence  so  far  presented  does  not  show  that  the  intestinal  lining  cells 
synthetize  the  amino-acids  into  the  proteins  of  the  blood,  which  in 
turn  would  have  to  be  changed  into  tissue  proteins.  Consequently, 
it  may  be  concluded  that  the  body  synthetizes  its  proteins  from  the 
amino-acids  directly,  using  in  this  case  only  those  which  are  of  special 
value  to  it.  The  others,  as  well  as  those  transferred  into  the  blood  by 
the  cells  as  waste,  are  split  into  two  portions,  one  of  which  represents 
the  ammonia  and  the  other  the  remnant  of  the  amino-acid  molecule. 
The  urea  is  derived  from  the  former,  while  the  latter  is  immediately 
oxidized  to  yield  energy.  For  this  reason,  we  commonly  speak  of  the 
so-called  tissue-protein  and  circulating  protein,  the  former  being  rep- 
resented by  that  portion  of  it  which  enters  the  cells  of  the  tissues  to 
become  an  intricate  part  of  them,  while  the  latter  is  broken  down 
immediately  without  having  been  converted  into  cellular  protoplasm. 


HISTORY    OF    DIFFEHENT    FOODSTIFFS    IN    IJODV  1049 

Tho  proportion  of  each  must,  of  courso,  differ  with  the  condition  of  the 
body.  If  (ho  latter  is  in  nUroqcu-iujiiilibrium,  a  more  considerable 
proportion  of  it  will  ])e  oxidized  ihi-ectly  to  yieldcnerpiy  than  when 
tlie  body  is  in  need  of  this  substance  to  make  good  a  previous  loss. 
Quite  similarly,  the  greater  the  amount  of  protein  taken  in  under  nor- 
mal conditions,  th(^  greater  must  be  that  amount  of  it  which  is  directly 
converted  into  energy. 

This  division  of  the  absorbed  proteins  into  tissue  and  circulating 
proteins  shows  that  their  catabolism  is  not  uniform,  but  consists  es- 
sentially of  two  separate  processes  (Liebig),  Obviously,  the  tissue 
catabolism  must  remain  rather  constant  under  normal  conditions, 
while  the  catabolism  of  the  circulating  proteins  nmst  differ  more  di- 
rectly with  the  amount  of  proteins  ingested.  Consequently,  any 
attempt  made  to  determine  the  metabolism  of  the  proteins  requires 
the  reduction  of  the  circulating  proteins  to  a  minimum.  Only  when 
this  end  has  been  accomplished  are  we  in  a  position  to  obtain  a  fair 
insight  into  the  protein  metabolism  of  the  tissues.  Any  analysis  of 
this  kind,  therefore,  must  take  into  account  first  the  so-called  exogenous 
'protein,  namely,  that  portion  of  it  which  is  derived  directly  from  the 
food,  and  secondly,  the  endogenous  protein,  which  is  the  result  of  the 
catabolism  of  the  substance  of  the  tissue  cells.  Clearly,  the  first  has 
really  little  to  do  with  the  life  of  the  cells,  while  the  latter  actually 
serves  as  a  measure  of  the  waste  of  the  tissues. 

The  Utilization  of  the  Proteins. — The  amino-acids  appear  in  the 
blood  in  amounts  scarcely  sufficient  for  a  quantitative  analysis.  Van- 
Slyke,  ^  however,  states  that  their  amount  is  fairly  constant  and  that  the 
fasting  animal  contains  from  3  to  5  mgr.  in  each  100  c.c.  of  blood. 
After  meals,  when  an  active  absorption  of  proteins  is  going  on,  their 
amount  may  be  doubled  and  similar  increases  jnay  be  obtained  by  the 
injection  of  amino-acids  into  the  intestine.  Thus,  10  grm.  of  alanin 
administered  in  this  way  yielded  as  much  as  6.3  mgr.  in  each  100  c.c. 
of  mesenteric  blood.  A  method  by  means  of  which  such  substances 
may  be  withdrawn  from  the  circulating  blood  has  been  described  by 
Abel. 2  It  is  known  as  vividiffusion.  The  apparatus  consists  of  a  long 
tube  of  collodion  coiled  upon  itself  and  immersed  in  a  solution  contain- 
ing approximately  the  same  content  in  salts  as  blood  plasma.  The 
ends  of  the  collodion  tube  are  connected  with  the  central  and  distal 
ends  of  an  artery.  As  the  blood  circulates  through  it,  its  diffusible 
constituents  dialyze  into  the  saline  solution  and  may  be  recovered 
from  the  latter.  In  this  way  it  has  been  possible  to  isolate  alamine 
and  vahne  in  crystalline  form,  and  also  to  detect  the  presence  in  the 
blood  of  histidine  and  creatine. 

It  is  a  well-known  fact  that  a  large  meal  of  protein  gives  rise  to  a 
rapid  increase  of  the  urea  in  the  urine  until  about  the  fifth  hour, 
when  at  least  50  per  cent,  of  the  total  nitrogen  of  the  food  will  have 
passed  into  the  urine.     If  we  consider  that  digestion  is  going  on  mean- 

^  Harvey  Lectures,  Xew  York,  Lippincott  and  Co.,  1916. 
2  The  Mellon  Lecture,  Science,  xlii,  1915,  135. 


1050  ABSORPTION 

while,  we  must  conclude  that  a  portion  of  the  nitrogen  of  the  food 
passes  over  almost  immediately.  Consequently,  urea  may  well  be 
employed  as  an  index  of  the  amount  of  protein  absorbed.  Even  the 
intravenous  injection  of  solutions  of  the  amino-acids  into  normal 
animals  docs  not  result  in  their  retention,  as  much  as  90  per  cent,  of 
the  original  amount  disappearing  from  the  blood  in  the  course  of  5 
minutes  after  the  injection.  These  facts,  as  well  as  others  that  might 
still  be  mentioned,  show  conclusively  that  the  amino-acids  do  not  tarry 
in  the  tissues,  but  are  rapidly  excreted  so  that  their  destruction  prac- 
tically equals  their  absorption.  This  need  not  surprise  us,  because  it 
has  been  shown  previously  that  the  tissue  proteins  are  equilibrated  in  a 
more  exact  manner  than  the  fat  and  carbohydrates,  and  that  a  definite 
relationship  must,  therefore,  be  retained  between  the  amino-acids  of 
the  blood  and  those  of  the  tissues.  But  while  the  power  of  protein- 
storage  of  the  tissues  is  extremely  limited,  it  seems  that  the  liver  is 
much  more  elastic  in  this  regard  and  is  capable  of  assimilating  125 
to  150  mgr.  per  100  gr.  of  the  original  amount.  Its  power  of  absorbing 
this  material  is  also  evinced  by  the  fact  that  the  concentration  of  the 
amino-acids  is  less  in  the  blood  leaving  this  organ  than  in  that  enter- 
ing it.^ 

The  deduction  to  be  made  from  these  data  is  that  the  liver  utilizes 
the  amino-acids  in  the  formation  of  urea.  But  since  this  body  may 
also  be  produced  after  the  removal  of  the  liver,  this  organ  cannot  be 
said  to  be  the  only  place  in  which  urea  is  formed,  although  it  is  safe  to 
conclude  that  it  is  its  chief  source.  Moreover,  since  it  is  the  endeavor 
of  the  system  to  remain  in  nitrogen-equilibrium,  it  is  the  function  of 
the  liver  to  prevent  any  flooding  of  the  tissues  with  amino-acids. 
Consequently,  this  organ  begins  its  function  of  forming  urea  almost 
immediately  after  these  substances  have  begun  to  be  absorbed. 
Besides,  the  liver  also  takes  care  of  the  protein  waste,  discharged  in 
consequence  of  the  catabolism  of  the  different  tissues. 

The  End-products  of  Protein  Metabolism,- — Obviously,  the  tissue- 
proteins  are  first  split  up  into  the  amino-acids  from  which  they  were  first 
synthetized,  and  supposedly  no  decisive  chemical  difference  exists 
between  these  catabolic  products  and  the  amino-acids  absorbed.  We 
know  that  the  tissues  possess  this  power  of  reducing  their  protein 
material,  because  they  are  in  possession  of  proteolytic  enzymes  (pro- 
teases) which  may  be  isolated  from  them  in  different  ways.  Thus,  it 
is  a  matter  of  common  experience  that  pieces  of  tissues,  when  kept 
under  proper  condition  of  temperature  and  moisture,  undergo  autolytic 
changes  which  yield  ammonia,  glycine,  tyrosine,  tryptolane  and  other 
basic  substances.  A  similar  process  of  autolysis  occurs  in  malignant 
tumors,  and  such  a  condition  as  cystinuria  merely  indicates  that  the 
cystin  is  not  taken  care  of  by  the  body,  owing  to  a  derangement  of 
the  metabolism  of  the  amino-acids.     It  enters  the  urine,  frequently 

1  Mendel,  Ergebn.  der  Physiol.,  1911. 


HISTORY    OF    DIFrEllENT    FOODSTUFFS    IX    IJODV  1051 

associated  with  loiiciiio  and  tyiosiiic.  whore  if  may  he  dopositod  in 
the  form  of  eak-uU. 

Whatever  interme(harv  slaj^es  tlie  amino-acids  may  pass  throuffh, 
they  are  finally  converted  into  carl)on  dioxid,  water,  and  ndatively 
simple  substances  containing  nitrogen,  ('hief  amonp;  the  latter  is  urea 
and  its  precursor  amnion  id,  hut  there  are  also  some  which  cannot  be 
regarded  as  members  of  the  amino-acid  group,  such  as  creatine  and 
creatinine.  These  bodies  are  very  largely  the  result  of  endogenous  pro- 
tein metabolism,  although  some  of  the  creatine  and  creatinine  of  the 
food  may  appear  as  such  in  the  urine.  Besides,  some  of  the  amino- 
acids  may  appear  in  the  urine  as  such,  giving  ris(^  to  the  so-called  amino- 
nitrogcn.  or  undetermined  nitrogen.  But  since  the  metabolism  of  the 
cells  also  includes  that  of  their  nuclear  material,  and  since  the  latter  is 
also  ingested,  for  example,  in  the  form  of  sweet-breads  or  thymus,  this 
list  should  be  augmented  to  embrace  the  purin  bodies.  The  determina- 
tion of  sulphur  in  the  urine  is  valuable  in  so  far  as  it  gives  a  fair  picture 
of  the  metabolism  of  the  proteins,  because  this  foodstuff  serves  prac- 
tically as  the  only  vehicle  for  its  entrance  into  the  body. 

The  purine  bodies  arise  from  purine.  The  first  product  of  the 
oxidation  of  this  body  is  hypoxanthine  from  which  adenine  is  derived. 
The  second  product  of  its  oxidation  is  xanthine  and  its  amino  deriva- 
tive guanine.  The  trioxypurine  is  uric  acid,  which  in  birds  and  reptiles 
is  the  chief  derivative  of  protein  metabolism.  Whether  this  substance 
is  also  excreted  by  the  mammals  in  important  amounts  is  still  a  ques- 
tion. ^  It  would  appear,  however,  that  the  urine  acquires  uric  acid 
and  also  a  certain  amount  of  purine  bases  after  a  copious  diet  of  meat 
and  especially  after  the  ingestion  of  glandular  material.  For  this 
reason,  Burian  and  Schur^  have  recognized  an  endogenous  and  exog- 
enous purine  metabolism,  the  former  having  to  do  with  the  reduction 
of  the  purine  of  the  tissues  and  the  latter  with  that  of  the  preformed 
purine  constituents  of  the  food  ingested.  In  general,  it  may  be  said 
that  the  exogenous  purine  bears  a  close  relation  to  the  purine  of  the 
urine.  If  it  accumulates  in  the  tissues  it  gives  rise  to  the  condition 
known  as  gout,  and  hence,  purine-rich  food  should  not  be  taken  by 
persons  who  suffer  from  this  metabolic  difficulty  or  tendency  (gouty 
diathesis).  More  recently,  it  has  also  been  shown  b}^  Ascoli  and  Izar^ 
that  purine  may  be  synthetized  in  the  mammalian  body  from  urea  and 
carbon-rich  residues,  two  molecules  of  the  former  uniting  with  a 
carbon  residue  containing  three  carbon  atoms.  This  purine  would  of 
course  be  endogenous  in  its  character. 

1  Jones,  Nucleic  Acid,  Monographs  in  Biochem.,  Longmans,  Green  and  Co., 
1914. 

2  Zeitschr.  phvsiol.  Chemie,  xxiii,  1897,  55. 

3  Ibid.,  xliii,  1911,  319. 


1052  ABSORPTION 

CHAPTER  LXXXVII 
THE  METABOLIC  REQUIREMENTS  OF  THE  BODY 

The  Effect  of  Starvation. — The  withholding  of  food  places  the 
animal  upon  its  own  resources.  The  tendency  must  then  be  to. 
conserve  its  most  important  metabolic  substances,  the  proteins,  and 
to  obtain  its  energy  from  the  carbohydrates  and  fats.  We  observe, 
therefore,  that  the  tissues  of  an  animal  really  fall  into  two  groups, 
namely,  those  which  form  the  metabolic  nucleus  of  the  body  and  those 
which  serve  principally  as  storehouses  for  energy-yielding  maiterial.' 
A  starving  animal  first  of  all  draws  upon  its  store  in  glycogen,  then 
upon  its  fat,  and  lastly,  as  an  emergency  measure,  upon  its  proteins. 

Obviously,  energy  must  be  produced  even  in  the  advanced  stages 
of  inanition,  but  naturally,  its  amount  must  then  be  slight,  because 
all  the  activities  of  the  body  are  greatly  reduced  during  this  period. 
This  in  itself  will  tend  to  conserve  the  resources  of  the  tissues.  Thus, 
inanition  gives  rise  almost  immediately  to  a  feeling  of  fatigue  and 
weakness  which  the  animal  complies  with  by  assuming  an  inactive 
position,  passing  its  days  in  sleep  and  semi-stupor.  The  rate  of 
respiration,  the  frequency  of  the  heart,  as  well  as  the  body- tempera- 
ture, are  those  of  a  resting  animal  and  remain  so  until  a  day  or  two 
before  death,  when  the  respiratory  and  cardiac  activities  are  greatly 
reduced  and  the  body-temperature  falls  very  markedly.  The  quan- 
tity of  the  urine  is  greatly  decreased,  and  so  is  its  content  in  urea. 
Feces  are  formed  until  about  the  time  of  death,  but  in  very  small 
amounts,  say,  .10  to  20  grm.  in  the  course  of  a  day.  Professional 
fasters,  however,  state  that  no  pain  is  experienced  at  any  time  during 
the  fast  and  that  the  uncomfortable  sensations  of  the  first  few  days 
disappear  very  quickly.  The  body-weight  decreases  steadily,  until  at 
the  end  of  10  days  this  loss  may  amount  to  about  1.0  or  1.5  per  cent, 
of  the  original  weight.  Naturally,  those  tissues  are  reduced  most 
which  contain  the  largest  amount  of  fat,  whereas  the  brain,  spinal 
cord,  heart,  lungs,  and  pancreas  suffer  least. 

This  discussion  shows  first  of  all  that  an  animal  which  is  in  posses- 
sion of  a  considerable  amount  of  fat  at  the  beginning  of  the  period  of 
starvation,  is  in  a  much  better  position  to  withstand  the  withdrawal 
of  food  than  one  not  protected  in  this  way.  Thus,  a  well-nourished 
dog  may  survive  a  period  of  starvation  lasting  4  weeks;  in  fact,  in 
some  instances  death  did  not  result  until  after  2  or  3  months.^ 
Succi,  the  professional  faster,  abstained  from  food  for  30  days,  and 
Marlatti  for  50  days.^     The  small  mammals  die  much  sooner,  and 

1  Falck,  Beitr.  zur  Physiol.,  Marburg,  1875,  and  Kumagawa,  Archiv  fiir 
Physiol.,  1898. 

'^  Luciani,  Das  Hungern,  1890. 


THK    METABOLIC    REQUIREMENTS    OF    THE    RODY  1053 

reptiles  and  amphibia  not  until  after  many  monlli.s  and  possiblj'  a 
year.  Secondly,  it  may  readily  be  {j;atheretl  tiiat  the  production  of 
heat  in  starvinf^-  animals  must  be  jj;i'eatly  reduced.  Thus,  the  profes- 
sional faster  C-etti'  rc(iuired  on  the  iirsi  tlay  only  '.V2A  calories  for  each 
kilogram  of  his  body-weij>;ht  and,  on  the  fifth  day,  only  30.0  calorics. 
Similar  values  have  been  found  by  Tigerstedt.^  In  accordance  with 
Rubner'  and  Magnus-Levy, •*  this  loss  of  energy  is  only  7  to  15  per 
cent,  lower  than  that  in  a  person  ingesting  a  moderate  amount  of  food. 

The  course  of  the  elimination  of  nitrocjcn  during  periods  of  star- 
vation is  closely  dependent  upon  the  condition  of  the  animal  at  the 
time  of  withholding  the  food.  If  the  animal  has  been  accustomed  to 
ingest  large  amounts  of  protein  material,  its  protein-catabolism  will 
be  rather  high  during  the  first  few  davs  of  the  period  of  starvation,  but 
a  uniformly  low  output  of  nitrogen  will  have  been  reached  at  the  end 
of  about  a  week.  Meanwhile,  its  store  in  glycogen  will  have  become 
exhausted,  while  its  fats  will  have  been  drawn  upon  incessantly  to 
shield  its  proteins.  As  soon  as  all  the  available  fat  has  become  ex- 
hausted, a  more  intense  metabolism  of  the  proteins  sets  in,  in  conse- 
quence of  which  the  output  of  nitrogen  is  increased.  This  'premortal 
rise  in  the  excretion  of  nitrogen  constitutes  an  unfavorable  diagnostic 
sign,  because  it  indicates  that  the  ordinary  fuel  of  the  animal  has  been 
thoroughly  depleted. 

In  the  herbivora,  conditions  are  somewhat  different,  because  these 
animals  possess  a  large  store  of  glycogen.  Thus,  it  is  commonly  found 
that  their  output  of  nitrogen  is  considerably  increased  during  the  first 
days  of  the  period  of  starvation,  because  since  they  have  been  accus- 
tomed to  use  carbohydrates  as  their  chief  fuel,  the  sudden  withdrawal 
of  this  foodstuff  forces  them  to  fall  back  upon  their  store  of  proteins. 
A  very  similar  reaction  takes  place  in  men  who  have  been  accustomed 
to  eat  large  amounts  of  carbohydrates.  In  both  instances,  therefore, 
starvation  changes  the  metabolism  into  a  type  more  nearly  like  that 
of  the  carnivorous  animals. 

The  ingo  of  oxygen  and  outgo  of  carbon  dioxid  soon  reach  a  minimal 
value.  Urea  nitrogen  falls  and  NH3N  rises,  but  the  total  amount  of 
creatinine  and  creatine,  which  form  peculiar  derivatives  of  the  meta- 
bolism of  muscle  tissue,  is  not  changed  materially.  The  excretion  of 
the  purines  is  decreased  at  first  and  then  increased,  owing,  in  all 
probability,  to  the  steady  destruction  of  the  nuclear  material.  As 
far  as  the  relation  of  the  sulphur  to  the  nitrogen  is  concerned,  it  is  to 
be  noted  that  their  ratio  is  at  first  as  17N:  IS,  and  later  on,  as  14. 5N :  IS. 
If  anything,  these  values  suggest  that  the  principal  source  of  protein 
during  the  later  stages  of  starvation  is  the  protein  material  of  muscle 
tissue. 

^  Virchow's  Archiv,  cxxxi,  1893;  also:  Benedict,  Carnegie  Inst,  of  Washington, 
No.  126,  1910. 

2  Skand.  Archiv  fiir  Physiol.,  vii,  1897,  29. 
2  Gesetze  des  Energieverbr.,  Leipzig,  1902. 
*  Pfluger's  Archiv,  Iv,  1894,  96. 


1054  ABSORPTION 

The  Effect  of  Sleep. — Sleep  does  not  affect  the  metabolism  of  the 
proteins  to  any  extent,  as  is  shown  by  the  fact  that  the  total  nitrogen 
excreted  remains  about  the  same.  Instead,  there  appears  a  slight 
reduction  in  the  output  of  endogenous  purine  nitrogen,  indicating  a 
lessened  destruction  of  nuclear  substances.  Contrariwise,  the  ingo 
of  oxygen  and  outgo  of  carbon  dioxid  are  markedly  diminished,  an 
indication  that  the  tonicitj^  and  activity  of  the  muscles  and  glands  are 
considerably  reduced. 

The  Effect  of  Temperature. — Within  narrow  limits  the  metr.bolism 
of  the  warm-blooded  animals  is  increased  by  a  cold  and  decreased  by 
a  warm  outside  temperature,  but  this  result  is  only  obtained  if  the 
body-temperature  is  not  greatly  altered  thereby.  Extreme  varia- 
tions in  the  outside  temperature,  which  in  turn  produce  a  material 
change  in  the  body-temperature,  affect  the  metabolism  in  a  reverse 
manner.  This  need  not  surprise  us,  because  the  body  constantly 
attempts  to  retain  its  normal  temperature  of  about  37.0°  C.  A  cooling 
of  the  air  gives  rise  to  a  greater  loss  of  heat  and  hence,  a  more  intense 
metabolism  must  immediately  be  instituted  to  counteract  this  effect. 
Contrariwise,  an  increased  temperature  of  the  atmosphere  lessens  the 
loss  of  heat  and,  consequently,  less  heat  need  be  produced.  But,  in 
case  this  heat-regulatory  mechanism  is  overcome,  an  excessive  fall 
in  the  body-temperature  invariably  diminishes  the  oxidations  and  heat 
production,  whereas  an  unusual  rise  increases  these  processes.  The 
body  having  been  sufficiently  cooled,  all  chemical  processes  within  it 
come  to  a  standstill.  Evidently,  in  the  presence  of  a  well-balanced 
heat-regulatory  mechanism,  any  deficiency  in  the  body-temperature 
is  made  up  at  the  expense  of  the  non-nitrogenous  constituents  of  the 
tissues.  This  is  shown  by  the  fact  that  the  consumption  of  oxygen 
and  elimination  of  carbon  dioxid  are  increased,  while  the  nitrogenous 
excretions  in  the  urine  remain  practically  the  same. 

The  Effect  of  Age  and  Sex. — The  output  of  energy  is  low  in  the 
new-born,  but  increases  rapidly  during  the  first  year  until  it  reaches 
its  maximal  value  at  about  the  sixth  year.  Subsequent  to  this  time, 
it  decreases  rather  rapidly  until  the  twentieth  year  and  then  more 
slowly  until  late  in  life.  This  steady  decline  is  interrupted  only  at 
the  time  of  puberty,  when  the  metabolism  is  temporarily  intensified. 
The  output  of  energ}^  by  the  female  is  about  4.3  per  cent,  below  that 
of  the  male. 

The  Effect  of  Muscular  Exercise. — The  metabolism  is  materially 
increased  even  by  ordinary  degrees  of  work,  although  the  protein 
waste  is  no  greater  than  during  rest.  After  excessive  exercise,  on  the 
other  hand,  the  latter  is  considerably  increased,  embracing  urea,  am- 
monia, creatinine,  and  even  uric  acid  and  purine  bases.  This  contra- 
dicts the  view  of  Liebig,  implying  that  the  greater  energy  hberated 
during  muscular  work  finds  its  source  in  a  break-down  of  the  muscular 
tissue,  and  must,  therefore,  be  performed  at  the  expense  of  an  increased 
metabohsm  of  the  proteins.     Such  a  result,  however,  is  never  obtained 


THE    METAHOLK      KKQr  I KKMENTS    OF    THE    IJODY  1055 

unless  the  animal  has  Ixm-h  iiourislKHl  oxclusivcly  on  protein  material 
and  is  not  in  possession  of  iioi-mal  amounts  of  ^lycofren  und  fat.  Thus, 
Voit  lias  found  lliat  an  ;ininial  which  is  in  fat  and  carhohyth-ate  e(|ui- 
librium  doesnot  exhibit  a  nitroj^t^nous  hreakchnvn.and  conchided,  there- 
fore, that  the  extra  energy  is  derived  wholly  from  the  non-nitrogenous 
constituents  of  the  body. 

These  results  soon  found  support  in  the  experiments  of  Fick  and 
Wisleeinus.  who  asceiKhxl  the  Faullioi-n  to  a  height  of  195G  meters. 
By  comparing  their  weight  with  the  height  to  which  they  climbed,  it 
was  possible  to  compute  the  amount  of  work  performed  by  each  of 
them.  In  the  case  of  Fick,  it  amounted  to  66  X  1956  =  120,006 
kilogrammeters  plus  about  30,000  kilogranuneters  of  work  perforined 
by  the  heart  and  muscles  of  respiration.  Since  only  non-nitrogenous 
food  had  been  ingested  by  these  investigators  during  a  period  of  17 
hours  before  the  climb  as  well  as  during  it,  the  urea  eliminated  by 
them  must  have  been  derived  entirely  from  their  body-proteins.  On 
determining  the  heat  value  of  this  urea,  it  was  found  to  be  entirely 
insufficient  to  account  for  the  amount  of  work  done.  Very  similar 
results  have  been  obtained  by  Parkes  upon  soldiers  during  periods  of 
rest  and  long  marches,  and  by  Atwater  by  means  of  the  respiration 
calorimeter. 

It  may  be  concluded,  therefore,  that  ordinary  muscular  work  does 
not  increase  the  metabolism  of  the  proteins  much  beyond  its  normal 
value,  provided  sufficient  non-nitrogenous  material  is  at  hand  to  pro- 
duce the  required  amount  of  extra  energy.  Accordingly,  if  the  non- 
nitrogenous  substances  are  present  in  insufficient  quantity,  some  of 
this  extra  energy  must  be  derived  from  the  proteins.  The  elimination 
of  nitrogen  in  the  urine  is  then  increased,  and  naturally,  this  waste 
must  be  the  greater  the  more  intense  the  muscular  exercise. 

Normal  Metabolism. — The  preceding  discussion  pertaining  to 
starvation  is  of  special  value,  because  it  furnishes  a  means  of  deter- 
mining the  amounts  of  energy  liberated  by  the  body  under  normal 
conditions,  and  allows  us  to  ascertain  the  amount  of  fuel  which  must 
be  ingested  in  order  to  supply  this  energy.  It  will  be  found  that  a 
marked  difference  exists  between  the  various  foodstuffs  in  this  regard. 
In  the  first  place,  it  should  be  noted  that  an  animal  fed  on  pure  fat 
or  carbohydrate,  or  a  mixture  of  the  two,  does  not  survive  this  diet 
for  a  much  longer  period  than  if  all  food  "were  withheld.  Consequently, 
this  diet  is  only  little  better  than  actual  starvation.  On  a  diet  of 
proteins,  salts  and  water,  on  the  other  hand,  the  animal  most  generally 
survives.  In  the  second  place,  it  is  not  correct  to  assume  that  an 
animal  may  be  kept  in  equilibrium  for  any  particular  foodstuff  if 
the  intake  is  exactly  balanced  with  the  waste. 

This  is  true  in  particular  of  the  proteins.  Thus,  if  a  starving 
animal  is  fed  an  amount  of  protein  which  exactly  balances  the  output 
of  nitrogen,  the  excretion  of  the  latter  rises  to  a  level  practically  equal 
to  that  of  starvation,  plus  that  of  the  protein  ingested.     This  implies 


1056  ABSORPTIOX 

that  the  waste  of  tissue-protoins  proceeds  as  before.  To  illustrate, 
if  a  dog  of  medium  size  excretes  on  the  fifth  day  of  starvation  about 
5  grm.  of  nitrogen,  this  loss  corresponds  to  a  combustion  of  31.25  grm. 
of  protein.  Now,  if  the  latter  amount  be  given  to  this  animal  as 
food,  it  will  excrete  nearly  10  grm.  of  nitrogen- waste.  In  order  to 
cause  this  animal  not  to  lose  more  nitrogen  than  it  receives,  or  better, 
in  order  to  place  it  in  nitrogen-equilibrium,  it  is  necessarj'  to  give  it  an 
amount  of  protein  the  nitrogen-content  of  which  is  at  least  two  and 
one-half  times  that  of  the  star\'ation  standard.  This  same  conclusion 
may  be  arrived  at  by  a  consideration  of  the  data  derived  from  profes- 
sional fasters.  Since  the  total  output  of  energy,  say,  on  the  fifth  day 
of  the  period  of  star\"ation,  amounts  to  1979  calories  and  the  output  of 
nitrogen  to  11.44  grm.,  it  requires  71.5  grm.  of  protein  to  meet  this  loss. 
But  71.5  grm.  of  protein  j-ield  only  293  calories  and  hence,  the  afore- 
said amount  of  energ}'  cannot  be  derived  entirely  from  this  protein. 
The  balance  must  be  suppHed  by  the  tissue-fat  and  glycogen.  Conse- 
quently, the  loss  in  the  substance  of  the  bod}'  cannot  be  stopped  by 
balancing  the  output  of  nitrogen  by  an  equal  ingestion  of  proteins. 
While  it  is  quite  simple  to  retain  by  this  means  the  nitrogen-equi- 
librium in  the  strictly  carnivorous  animals,  it  cannot  be  kept  in  this 
way  by  the  herbivora  and  omnivora. 

Since  man  belongs  to  the  latter  class  and  requires  about  3000 
calories  for  his  daily  work,  it  will  be  seen  that  at  least  3  lbs.  of  lean 
meat  must  be  ingested  bj'  him  in  order  to  supply-  this  amount  of  heat, 
1  lb.  of  meat  yielding  less  than  1000  calories.  But  this  method  of 
furnishing  the  necessary  energy  for  the  body  soon  overtaxes  the  organs 
of  metabolism  and  places  the  person  in  the  condition  of  partial  starva- 
tion. These  facts  form  the  basis  of  Banting's  cure^  for  obesity  which, 
by  the  ingestion  of  lean  meat,  attempts  to  give  the  feeling  of  satisfac- 
tion connected  with  a  "square"  meal,  and  at  the  same  time  causes 
the  body  to  burn  up  its  reserve  materials,  retaining  as  far  as  possible 
its  proteins. 

If  the  starving  animal  is  fed  a  mixed  diet  instead  of  pure  protein, 
it  is  able  to  retain  its  nitrogen-equihbrium  with  much  less  difficulty, 
because  the  ingestion  of  the  proteins  can  then  be  made  to  approximate 
the  waste.  The  carbohydrates  and  fats  are  protein  sparers.  This  is 
true  especially  of  the  carbohydrates,  because  it  has  been  shown  that  the 
combustion  of  proteins  during  starvation  may  be  greatly  reduced  bj'  the 
ingestion  of  this  foodstuff.  Thus,  the  administration  of  a  large  meal  of 
carbohydrates  to  a  starving  animal  may  raise  its  respiratory  exchange 
20  to  30  per  cent.  Furthermore,  it  is  possible  by  this  means  to  reduce 
the  daily  output  of  nitrogen  in  men  who  partake  of  an  average  diet 
of  from  15  grm.  to  6  grm.  and  less,  without  causing  them  to  lose  their 
nitrogen-equihbrium.  The  amount  of  carbohydrate  ingested  must,  of 
course,  balance  the  normal  daily  expenditure  of  energy.  This  subject 
msiy  also  be  approached  the  other  way,  i.e.,  by  determining  the  amount 

^Advocated  by  Wm.  Banting,  an  undertaker  of  London,  1797-1878. 


THE    MET.VBOLIC    REQUIREMENTS    OF    THE    BODY  1057 

of  protein  wliich  uiiist  be  ingested  in  order  to  bring  a  p(u-.son  into  nitro- 
gen-equilibrium. To  attain  this  end  we  need  30  grm.  of  the  proteins 
of  meat,  31  grm.  of  (he  proteins  of  milk,  54  grm.  of  (he  i)ro(eiiisof  beans, 
70  grm.  of  the  proteins  of  bread,  and  102  grm.  of  the  proteins  of  corn. 
This  outline  shows  very  clearly  that  the  proteins  of  the  vegetables 
are  not  so  easily  assimilated  as  those  of  meat. 

Excessive  Metabolism. — The  body  safeguards  itself  against  possi- 
ble disorders  in  its  metabolism  first  l)y  (he  (piality  and  secondly,  by  the 
quantity  of  the  food.  It  constantly  endeavors  to  retain  a  normal 
balance  sheet.  Under  ordinary  conditions,  however,  more  material 
is  ingested  than  is  actually  required  to  preserve  its  metabolic  equi- 
librium. This  fact  has  led  some  physiologists  to  believe  that  a  certain 
lux2is  consumption  is  a  necessity  in  order  to  allow  for  a  definite  waste. 
Any  excessive  ingestion,  on  the  other  hand,  leads  as  a  rule  to  a  certain 
deposition  of  the  superfluous  material  in  the  tissues.  Thus,  if  a 
normal  animal  is  given  excessive  amounts  of  fats  and  carbohydrates, 
a  large  portion  of  these  foodstuffs  is  converted  into  gl3'cogen  and 
tissue-fat  without  materially  increasing  the  general  metabolism.  In 
the  case  of  hyper  amounts  of  proteins,  however,  no  significant  storage 
takes  place,  and  by  far  the  largest  part  of  this  substance  is  excreted 
directly.  Consequently,  the  output  of  nitrogen  may  be  employed 
as  an  index  of  the  amount  of  protcnns  ingested. 

This  fact  shows  very  clearly  that  a  luxus  consumption  in  the  case  of 
proteins  cannot  serve  an  important  purpose,  and  is  very  expensive  be- 
sides. Chittenden  has  proved  that  a  normal  nutritive  condition  may  be 
attained  on  a  mixed  diet  containing  only  7  grm.  of  nitrogen  daily.  Men 
partaking  of  this  diet  followed  their  ordinary  vocations  without  diffi- 
culty, and  yielded  from  32  to  35  calories  per  kiloof  their  body-weight. 
In  fact,  when  somewhat  larger  quantities  of  carbohydrates  and  fats 
were  given,  the  nitrogen  ingo  could  be  reduced  to  5  grm.  daily  (33 
grm.  of  protein).  While  these  experiments  indicate  that  a  normal 
person  can  get  along  with  less  protein  than  he  usually  takes,  the  ques- 
tion as  yet  to  be  decided  is:  should  he  actually  so  deprive  himself 
for  his  own  benefit?  Quite  aside  from  an  actual  luxus  consumption, 
the  answer  might  be  that  a  material  reduction  in  the  ingo  of  pro- 
tein material  would  undoubtedly  lower  the  resistance  of  these  persons, 
at  least  in  the  course  of  time.  Much  also  depends  upon  the  quality 
of  the  protein.  The  accepted  view,  however,  is  that  a  reduction  in 
the  intake  of  proteins  of  one-third  to  one-half  might  be  effected  without 
injury  and,  naturally,  this  necessary  minimum  of  about  50  to  60 
grm.  of  proteins,  instead  of  the  usual  100  to  150  grm.,  must  be  sup- 
plied in  the  form  of  meat  and  vegetables  to  the  exclusion  of  neither. 
As  has  been  stated  above,  much  larger  amounts  of  the  latter  must  be 
ingested  in  order  to  furnish  the  same  amount  of  energy. 

The  foregoing  discussion  must  have  shown  that  an  animal  may  be 
in  nitrogen-equilibrium  and  not  in  carbon-equilibrium.  The  latter, 
however,  is  not  so  important,  because  the  quantity  of  fat  may  vary 

67 


1058 


.\BSORPTION 


considerably,  while  the  nitrogen  content  remains  practically  the  same. 
Obviously,  a  gain  in  carbon  means  a  gain  in  fat,  and  vice  versa.  In 
the  carnivorous  animals,  the  carbon-equilibrium  is  retained  on  an 
abundant  protein  diet,  but  this  foodstuff  must  be  supplied  in  excessive 
amounts.  Thus,  Voit  has  shown  that  the  larger  carnivora  need  at 
least  1500  grm.  of  meat  daily  to  prevent  a  loss  of  carbon.  For  a 
man  weighing  70  kilos,  this  would  mean  an  ingestion  of  2000  grm. 
of  lean  meat,  and  a  combustion  and  elimination  of  nitrogen  about  three 
times  greater  than  normal.  Obviously,  a  metabolism  of  this  kind 
could  not  be  continued  for  anj^  length  of  time.  This  again  shows  the 
necessity  of  a  mixed  diet,  as  being  more  beneficial  and  economical. 


CHAPTER  LXXXVIII 

THE  NUTRITIVE  VALUE  OF  FOOD 

The  Normal  Diet  of  Man. — The  quantity  of  food  which  is  required 
to  keep  a  person  in  a  condition  of  health  is  determined  by  its  power 
of  sustaining  the  energy  which  he  is  called  upon  to  liberate.  While 
the  latter  must  vary  considerably  with  the  activities  of  the  body, 
we  may  adhere  rather  closely  to  the  data  of  Rubner  which  show  the 
following  energy  requirements: 


Weight,  kilos 

Area,  sq.  m. 

Calories 

Calories  per  kg. 

80 

2283 

2864 

35.8 

70 

2088 

2631 

37.7 

60 

1885 

2368 

39.5 

50 

1670 

2102 

42.0 

40 

1438 

ISIO 

45.2 

Thus,  it  will  be  seen  that  a  vigorous  man  weighing  70  kilos  necessi- 
tates close  to  37  calories  for  each  kilogram  of  weight,  or  about  2600 
calories  in  all.  During  starvation  this  same  person  needs  32  calories 
per  kilogram,  or  2200  calories  in  all.  Consequently,  the  ordinar}-  re- 
quirement is  about  14  per  cent,  above  that  of  starvation.  In  order  to 
supply  this  energy,  \'oit  gives  the  following  ration  for  the  use  of  work- 
men performing  8  to  9  hours  of  work:  proteins  118  grm.,  fat  50  grm., 
and  carbohydrate  500  grm.  This  would  yield  3055  calories  which, 
owing  to  a  certain  non-utilization,  may  be  reduced  to  about  2700 
calories.  Rubner  allows  127  grm.  of  protein  and  Atwater^  125  grm. 
for  this  class  of  workmen.     Furthermore,  in  the  case  of  severe  work 

1  Physiologie  des  Stoffwechsels,  1881. 

^  Mem.  of  the  Nat.  Acad,  of  Sciences,  Washington,  1902. 


THi:    Nl'TRITrVE    VALUE    OF    FOOD  1059 

this  supply  must  be  iucrcasocl  considcialtly,  tluis:  proteins  lii")  j>;nn., 
fat  80  grin.,  anil  carbohydrate  500  grni.  This  represents  a  total  value 
of  334,S  calories. 

It  will  be  observed  that  the  amount  of  protein  reniains  fairly  eon- 
stant,  while  the  proport  ion  of  earboiiytlrato  and  fat  varies  considerably. 
Moreover,  these  nutritive  substances  nuiy  be  substituted  for  one  an- 
other within  narrow  limits,  but  none  of  them  should  be  eliminated 
from  the  diet  altop;ether,  because  the  retention  of  perfect  health  re- 
quires the  ingestion  of  a  certain  minimum  amount  of  each.  Various 
other  factors  must  also  be  considered.  For  example,  if  there  has 
been  a  loss  of  protein  material  from  one  cause  or  another,  it  is  impera- 
tive to  ingest  an  extra  amount  of  protein  to  allow  for  its  storage  in 
the  form  of  tissue  proteins.  Quite  similarly,  it  is  desirable  to  increase 
the  protein  metabolism  during  periods  of  training,  when  a  perfect 
stability  of  the  musculature  is  to  be  attained.  A  limited  reduction 
in  the  amount  of  the  protein  is  justifiable  only  in  vigorous  persons. 

Whether  the  prerequisite  amount  of  protein  is  derived  from  animal 
food  or  from  vegetables  is  rather  immaterial,  although  much  quicker 
results  are  obtained  with  the  former.  Both  have  their  advantages 
and  disadvantages.  While  vegetables  are  efl&cient  protein  producers, 
much  larger  quantities  of  them  must  be  ingested  in  order  to  yield  the 
same  degree  of  energy.  In  the  end,  this  may  not  prove  to  be  an  eco- 
nomical advantage,  at  least  not  at  the  present  time.  They  possess, 
however,  certain  stimulating  qualities  upon  peristalsis  and  bring  into 
the  body  a  greater  variety  of  proteins  than  could  possibly  be  introduced 
by  meat  alone.  It  appears,  therefore,  that  the  ordinary  person  should 
partake  of  a  mLxed  diet  rather  than  of  one  strictly  vegetarian  in  its 
character. 

It  has  been  observed  by  Rubner  that  a  starving  animal,  w^hen  fed 
with  carbohydrate,  shows  an  increase  in  its  heat  production  of  from 
30  to  40  per  cent.  The  feeding  of  meat  also  gives  rise  to  an  increase 
under  this  condition,  but  the  increase  is  then  almost  three  times 
greater.  It  will  be  seen,  therefore,  that  the  proteins  are  actual  stimu- 
lants of  metabolism  and  possess  for  this  reason  a  specific  dynamic 
action  upon  the  organs  of  metabolism. 

The  Factor  of  Growth. — In  accordance  wdth  the  well-established 
fact  that  the  intensity  of  the  metabolism  increases  inversely  with  the 
size  of  the  animal,  it  cannot  surprise  us  to  find  that  children  must  com- 
pensate for  a  much  greater  expenditure  of  energy  than  adults.  Small 
animals  invariably  lose  more  heat  in  proportion  to  the  mass  of  their 
body  than  large  ones,  although  area  for  area  of  their  body-surface 
their  dissipation  of  heat  is  practically  the  same.  In  order  to  make  up 
for  this  greater  loss  of  heat,  children  must  be  more  active.  This  is 
true  especially  of  boys  before  the  age  of  puberty.  In  addition,  it  is 
not  at  all  improbable  that  a  second  factor  is  at  work  at  this  time  in  the 
form  of  some  stimulus  derived  from  energized  and  growing  protoplasm. 
Thus,  a  body  between  the  ages  of  nine  and  fourteen  requires  as  much 


1060  ABSORPTION 

food  as  an  adult,  and  between  the  ages  of  fourteen  to  nineteen  even 
more  than  that.  In  the  females  there  is  a  smiilar  absolute  increase 
to  about  the  eleventh  year,  when  it  becomes  more  constant  and  equals 
about  that  of  a  woman  of  thirty.  These  brief  data  show  very  clearly 
that  the  total  energy  and  food  requirements  of  the  young  animal  are 
higher  than  those  of  the  adult.  In  the  second  place,  it  has  been  made 
evident  by  the  work  of  MendeP  and  others  that  growing  tissues  de- 
mand not  only  an  abundance  of  protein,  but  proteins  of  the  proper 
kind. 

This  statement  leads  us  to  infer  that  a  diet  may  be  well  balanced, 
as  far  as  the  ingo  and  outgo  of  the  proteins  are  concerned,  and  yet  fail 
absolutely  in  suppljdng  those  substances  which  are  absolutely  essential 
to  growth.  Thus,  it  has  been  shown  by  Osborne,  McCollum  and 
others  that  such  proteins  as  legumelin  (soy  bean) ,  gliadin  (wheat  and 
rye),  legumin  (pea),  hordein  (barlejO,  zein  (maize),  and  phaseolin 
(kidnej^  bean)  may  maintain  life,  but  prove  quite  insufficient  for 
growth.  Other  proteins  which  are  capable  of  sustaining  growth  are 
glycinin  (soy  bean) ,  glutein  (wheat) ,  glutelin  (maize) ,  globulin  (squash 
seed),  edestin  (hemp  seed),  and  casein.  In  the  case  of  casein  it  is  of 
interest  to  note  that  it  does  not  contain  glj^cocoll,  one  of  the  simplest 
of  the  amino-acids,  but  this  deficiency  does  not  prove  disturbing, 
because  the  body  is  in  a  position  to  synthetize  this  substance  from 
other  sources.  Just  the  opposite  result  follows  the  withdrawal  of 
cystine,  which  the  body  cannot  build  up  and  must,  therefore,  obtain  in 
an  available  form.  Quite  similarly,  the  tissues  may  be  maintained 
in  their  present  condition  without  Ij'sine,  although  they  cannot  grow 
in  its  absence.  This  substance  seems  to  be  a  requirement  of  all 
growing  tissues,  because  it  is  present  in  large  amounts  in  casein, 
lactalbumin  and  egg  vitellin.  It  will  be  seen,  therefore,  that  the  body 
demands  a  mixture  of  protein  foodstuffs  from  which  it  may  then  select 
those  amino-acids  which  are  most  essential  for  its  growth.  An  ex- 
clusive vegetable  diet  might  easily  prove  insufficient,  because  it  lacks 
the  aromatic  amino-acids,  tyrosine  and  tryptophane,  the  diamino- 
acid,  lysine,  and  the  sulphur  amino-acid,  cystine.  But  this  is  also 
true  of  certain  proteins  of  animal  origin;  for  example,  gelatin,  which 
for  this  reason  cannot  be  regarded  as  an  adequate  food. 

Since  milk  is  practically  the  sole  food  of  the  growing  mammal,  we 
should  expect  to  find  its  content  in  proteins  to  correspond  closely  to 
the  above  principles.  In  support  of  this  contention  it  might  be  men- 
tioned that  the  analyses  of  milk  from  different  animals  have  shown 
that  the  protein  content  of  this  secretion  varies  with  the  speed  with 
which  their  young  grow.  For  example,  since  the  infant  doubles  its 
weight  in  about  180  days  and  the  kitten  in  7  days,  human  milk 
contains  only  1.6  per  cent,  of  protein  and  that  of  the  cat  9.5  per  cent. 
Furthermore,  the  infant  receives  a  relatively  much  greater  proportion 
of  protein  than  the  adult  and,  besides,  an  excess  of  fat  in  order  to  be 

^  Harvey  Lectures,  Lippincott  and  Co.,  New  York,  1915. 


THE    NUTRITIVE    VALI'E    OF    FOOD  1061 

able  to  utilize  the  former  as  tissue-protein  and  to  burn  the  latter  to 
produce  heat.  In  view  of  the  larger  body-surface  of  the  infant  and 
its  more  intense  metabolism,  such  a  relationship  is  rather  to  be  ex- 
pected. Milk  is  also  rich  in  calcium  and  phosphorus,  a  peculiarity 
which  greatly  favors  the  growth  of  the  skeleton. 

The  Inorganic  Salts. — So  far  special  attention  has  been  paid  to 
the  carboliydnites,  fats  and  proteins.  It  is  to  be  noted,  however, 
that  an  animal  which  receives  these  foodstuffs  without  the  salts, 
succumbs  even  more  rapidly  than  one  fed  with  an  absolutely  inade- 
quate diet.  Evidently,  the  inorganic  constituents  are  as  important 
for  the  maintenance  of  life  as  the  organic  constituents,  and  this  in 
spite  of  the  fact  that  they  do  not  yield  energy.  They  are  absolutely 
essential  to  the  body  for  the  reason  that  they  help  in  maintaining  the 
composition  and  osmotic  pressure  of  the  body-fluids  and  determine, 
therefore,  the  interchanges  of  its  metabolites.  Secondly,  they  form 
essential  constituents  of  the  frame-work  of  the  body  and  even  enter 
into  the  composition  of  its  soft  parts.  Thus,  it  will  be  found  that 
the  incineration  of  the  body  yields  about  4.3  to  4.4  per  cent,  of  its 
weight  in  ash.  Of  this  amount,  five-sixths  must  be  apportioned  to 
the  bones  and  one-sixth  to  the  soft  parts.  The  ash  consists  of  the 
chlorids,  phosphates,  sulphates,  carbonates,  fluorides  and  silicates  of 
potassium,  sodium,  calcium,  magnesium  and  iron.  Besides,  iodin  occurs 
in  the  tissue  of  the  thyroid  gland.  It  is  also  evident  that  the  potassium 
salts  belong  more  particularly  to  the  organized  elements  of  the  tissues, 
whereas  the  sodium  salts  are  more  directly  concerned  with  the  com- 
position of  the  body-fluids,  and  the  calcium  salts  with  that  of  the  bones. 

In  the  latter  case,  it  has  been  demonstrated  beyond  doubt  that  a 
diet  poor  in  calcium  gives  rise  to  rickets,  a  condition  characterized  by 
a  deficient  and  imperfect  growth  of  the  bones.  In  adult  life,  most  of 
the  calcium  ingested  is  again  excreted  in  the  feces  and  urine,  although 
an  excessive  storage  may  result  later  on  which  leads  to  a  brittle  condi- 
tion of  the  bones  and  calcareous  infiltrations  of  different  tissues,  such 
as  the  walls  of  the  blood-vessels.  Iron  enters  the  body  in  organic 
combination,  and  it  is  still  a  much  debated  question  whether  inorganic 
iron  can  actualh^  be  taken  up  and  converted  into  so  complex  a  sub- 
stance as  hemoglobin. 

Bunge^  has  called  attention  to  the  fact  that  man  and  the  carnivor- 
ous animals  have  no  especial  longing  for  salts,  whereas  the  herbivora 
and  vegetarians  seek  it  eagerly.  With  the  exception  of  sodium  chlo- 
rid,  however,  these  salts  are  taken  into  our  sj^stem  unconsciously 
in  combination  with  the  different  foodstuffs,  but  the  addition  of  con- 
siderable amounts  of  the  former  to  our  food  does  not  seem  to  be  a 
necessity,  inasmuch  as  1  to  2  grm.  of  it  suffice  for  ordinary  pm-poses. 
Consequently,  the  daily  ingestion  by  the  average  man  of  10  grm.  of 
this  salt  may  rightly  be  considered  to  be  far  in  excess  of  his  actual 
needs.  Bunge  explains  this  large  intake  of  sodium  chlorid  by  saying 
^Physiol,  des  Menschen,  1001. 


1062  ABSORPTION 

that  the  potassium  sulphate,  which  is  so  abundant  in  vegetables  in- 
teracts with  the  sodium  chloiid  of  the  blood,  forming  potassium  chlo- 
rid  and  sodium  sulphate.  Both  salts  are  then  removed  in  the  urine 
and  hence,  it  becomes  imperative  to  renew  the  sodium  chlorid  content 
of  the  blood  repeatedly  in  order  to  keep  it  fairly  constant. 

Accessory  Factors. — Besides  the  digestibility  and  nutritive  value 
of  the  diet,  practical  dietetics  must  also  pay  attention  to  its  palata- 
bility.  This  involves  cooking  and  the  addition  to  the  food  of  flavors, 
condiments  and  stimulants.  The  first  factor  is  important  first  of  all 
from  an  economic  standpoint,  because  it  tends  to  render  the  cheaper 
foods  more  available  and  to  decrease  the  perfectly  appalling  waste  of 
all  food.  Secondly,  it  makes  the  food  more  appetizing  and  destroys 
its  indigestible  envelopes  so  that  the  digestive  juices  are  able  to  attack 
the  nutritive  material  directly.  Thirdly,  it  destroys  parasites  and 
microorganisms  and  those  antibodies  which  might  inhibit  the  action 
of  the  digestive  juices.  Thus,  it  is  a  well-known  fact  that  raw  white 
of  egg  is  not  digested  in  the  stomach,  because  it  contains  an  antibody 
which  hinders  the  action  of  the  pepsin,  while  a  finely  divided  boiled 
egg  is  more  rapidly  acted  upon  by  this  enzyme.  Lastly,  cooking  is 
of  importance  because  it  renders  the  food  more  bulky  and  macerates 
the  cellulose  material  of  green  food  so  that  it  can  be  more  advanta- 
geously utilized  as  ballast  for  the  feces.  This  in  itself  stimulates  peri- 
stalsis and  liberates  certain  substances  possessing  a  laxative  action. 

The  flavors  and  condiments  have  no  especial  food-value,  but  are 
of  importance  because  they  make  the  food  more  appetizing.  They 
are  divided  into  (a)  aromatics,  inclusive  of  such  substances  as  cinna- 
mon, vanilla  and  nutmeg,  (6)  pepper,  (c)  alliaceous  substances,  such 
as  garlic  and  mustard,  {d)  acid  condiments,  such  as  pickles,  vinegar 
and  citron,  (e)  salty  substances,  such  as  the  ordinary  table  salt,  and 
(/)  sugar. 

The  stimulants  consist  of  wine,  beer,  tea,  coffee,  chocolate  and 
cocoa.  While  some  of  these  contain  considerable  amounts  of  nutritive 
material,  their  principal  action  is  very  similar  to  that  of  the  condiments, 
i.e.,  they  render  the  food  appetizing  and  stimulate  the  secretions. 
However  nourishing  a  food  may  be,  it  eventually  produces  an  antago- 
nistic effect  unless  mixed  with  these  stimulants.  Thus,  the  rind  of  the 
bread,  the  skin  of  fruits,  and  extracts  of  meat  are  almost  as  important 
as  the  foodstuffs  contained  in  these  articles  of  diet.  Besides,  such 
articles  as  beer  and  cocoa  possess  a  distinct  nutritive  value,  although 
they  do  not  form  an  adequate  food  when  ingested  alone.  Thus,  14 
liters  of  beer  would  be  required  to  yield  15  grm.  of  nitrogen,  and  10 
liters  of  it  to  furnish  250  grm.  of  carbon.  In  the  case  of  cocoa,  we  obtain 
as  much  as  50  per  cent,  of  fat,  4  per  cent,  of  starch  and  13  per  cent,  of 
proteins,  but  excessive  quantities  would  have  to  be  consumed  in  order 
to  satisfy  our  caloric  needs.  Its  stimulating  alkaloid  is  theobromine 
or  dimethyl  xanthin  (C7H8N4O2),  which  exerts  a  tonic  action  upon  the 
nervous  and  vascular  system  similar  to  that  of  caffeine. 


THE    MTHITIVK    VALUE    OF    FOOD  1063 

The  usual  stimulant  taken  by  healthy  persons  is  coffee  or  tea.  In 
addition  to  ethereal  oil,  tannic  acid  and  other  siibstjinccs,  these  articles 
contain  tlie  alkaloid  caffeine  (Kunfi;e,  1820j  or  llieiiie.  ('ofTee  differs 
from  tea  in  being  rich  in  aromatic  materiul  (call'eal).  Tea  contains 
a  bitter  substance,  tannin,  and  hence,  it  should  not  be  allowed  to  draw 
for  longer  than  a  few  minut(>s,  otherwise  too  nuich  tannin  will  enter 
the  solution  and  pnxhice  injurious  effects.  Simihii- stinuihiting  drinks 
are  the  mate  of  Paraguay,  the  guarana  of  Brazil,  the  bush-tea  of 
South  Africa,  and  the  cola  of  Central  Africa.  Not  being  in  possession 
of  caffeine  plants,  the  inhabitants  of  Mexico  derive  their  stimulating 
beverage  from  the  fermented  seeds  of  the  chocolate  plant  which  contain 
theobromine. 

Among  the  alcoholic  stimulants  might  be  mentioned  the  malt 
liquors,  red  and  white  wines,  fortified  wines,  distilled  liquors,  or  spirits, 
and  elixirs.  Having  a  great  affinity  for  water  and  being  a  .coagulant 
of  protein,  alcphol  tends  to  destroy  the  cells.  It  should,  therefore,  be 
regarded  essentially  as  a  protoplasmic  poison.  Regarchng  its  action 
as  a  stimulant  and  its  value  as  a  food,  the  reader  must  be  referred  to 
the  more  specialized  literature  upon  this  subject,  because  it  is  alto- 
gether too  contradictory  and  extensive  to  be  included  in  a  book  of 
this  kind.^  In  general,  however,  it  may  be  said  that  alcohol  does  not 
build  up  the  tissues,  although  it  may  serve  to  spare  and  to  replace  fats 
and  carbohydrates  for  a  time  and  also  to  protect  the  proteins.  For 
this  reason,  it  may  be  considered  as  an  adjunct  article  of  diet  but  not 
as  a  true  food.  Obviously,  its  properties  of  yielding  energy  are  com- 
pletely overshadowed  by  its  pharmacologic  actions  as  a  depressant  and 
irritant. 

^  Welch,  "The  Pathological  Effects  of  Alcohol;"  Abel,  "Tlie  Pharniac.  Action 
of  Alcohol,"  and  Atwater,  "The  Nutritive  Value  of  Alcohol,"  in  Physiol.  Aspects 
of  the  Liquor  Problem,  1903. 


SECTION  XXVIII 
EXCRETION 

CHAPTER  LXXXIX 
THE  SECRETION  OF  URINE 

General  Discussion. — The  term  excretion  is  commonly  applied  to 
that  process  which  purposes  to  remove  the  waste  products  from  the 
body.  Living  matter  undergoes  constant  metabohc  changes,  and  it  is 
essential  that  the  substances  formed  in  the  course  of  these  processes 
be  removed  as  quickly  and  thoroughly  as  possible.  But  this  state- 
ment does  not  imply  that  the  substances  previously  taken  into  the 
body,  are  simply  split  into  their  components  and  excreted,  because  in 
several  instances  the  end-products  are  first  converted  into  by-products 
by  synthesis.  In  other  words,  excretion  should  not  be  thought  of  as 
a  passive  elimination  of  the  simple  constituents  of  the  food,  but  rather 
as  an  active  cellular  synthesis.  It  is  also  evident  that  this  process 
must  concern  itself  with  the  elimination  not  only  of  fluids,  but  also  of 
semi-solid  material  as  well  as  of  gases,  and  this  is  true  of  each  in- 
dividual cell  as  well  as  of  the  body  as  a  whole.  Thus,  cellular  dis- 
similation counterbalances  cellular  assimilation,  whereas  excretion 
counterbalances  the  nutritive  material  ingested. 

On  the  excretory  side  of  metabolism  matters  are  relatively  simple, 
because,  while  gases  and  liquids  of  varying  composition  are  in- 
volved, the  number  of  the  excretory  channels  may  really  be  reduced 
to  four,  namely,  the  skin,  lungs,  alimentary  canal  and  kidneys.  The 
chief  gaseous  excretion  is  furnished  by  the  lungs  in  the  form  of  carbon 
dioxid.  It  constitutes  the  final  stage  in  the  elimination  of  the  carbon 
of  the  absorbed  food.  The  principal  fluid  excretion  is  furnished  by  the 
kidneys  in  the  form  of  the  urine,  which  contains  the  hydrogen  and 
unchanged  water  of  the  food  as  well  as  the  various  end-products  of 
protein  metabolism.  But  the  hydrogen  and  unchanged  water  of  the 
food  are  also  eliminated  by  the  skin,  lungs,  intestinal  canal  and,  in  a 
small  measure,  also  by  the  nasal  mucosa,  lacrimal  glands  and  mucous 
glands.  The  undigested  and  unabsorbed  portions  of  the  food,  as  well 
as  certain  true  excretory  materials,  are  eliminated  in  the  feces. 

The  Structure  of  the  Kidney. — The  urinary  organs  embrace  the 
two  kidneys,  the  two  ureters,  and  the  urinary  bladder  with  the  urethra. 
In  man  each  kidney  is  .invested  by  a  fibrous  capsule  and  is  deeply 
imbedded  in  the  fatty  tissue  of  the  lumbar  region.     Its  capsule  is  only 

1064 


THE    SECRETION    OF    ITRINE 


1065 


slightly  adherent  lo  its  substance  and  is  continued  onward  as  the 
external  coat  of  the  upper  and  dilated  segment  of  the  ureter.  In 
transverse  section  each  ki(hiey  presents  two  i-atlier  siiarply  differen- 
tiated portions,  namely,  an  outer  or  cortical  and  an  inner  or  metlullary. 
This  difference  in  the  appearance  of  its  cut  surface  is  due  to  the  peculiar 
distribution  of  the  urinary  tubules,  of  which  practically  its  entire 
substance  is  composed.  Consequently,  it  may  be  said  that  the 
kidney  is  a  compound  tulmlar  j^land,  th(>  individual  secretory  units 
of  which  are  directed  radially  outward  from  a  common  central  reser- 
voir, known  as  the  pelvis.  For  this  reason,  the  beginning  portion,  or 
glomerulus,  of  each  urinary  tubule  must  come  to  lie  much  closer  to 


Fig.  522.  Fig.  523. 

Fig.  522. — Diagraaimatic  View  of  the  Kidney  in  Longitudinal  Section,  Showing 

THE  AeRANGEMENT  OF  THE  UrINIFEKOUS  TuBULES. 

G,   Glomerulus;  P,  pelvis;  V,  ureter;  C,  cortical  substance;  M,  medullary  substance. 
Fig.  523. — Glomerulus  with  the  Beginning  Segment  of  the  Uriniferous  Tubule. 
G,  Glomerulus;  A  and  E,  afferent  and  efferent  blood-vessels;  C,  capsule  of  Bowman; 
A'',  neck  oi  uriniferous  tubule;  CT,  distal  convoluted  tubule. 

the  surface  of  the  organ  than  its  collecting  segment.  The  renal  cortex, 
therefore,  is  made  up  principally  of  the  glomeruli  and  distalmost  por- 
tions of  the  uriniferous  tubules,  while  the  medulla  contains  chiefly 
the  smaller  and  larger  collecting  channels  as  they  strive  to  attain  the 
cavity  of  the  pelvis. 

Each  tubule  begins  as  a  dilatation  in  which  is  suspended  a  coil  of  capillaries. 
The  former  constitutes  the  capsule  of  Bowman  and  the  latter  the  corpuscle  of  Mal- 
pighi.  At  its  point  of  exit  from  this  enlargement  the  tubule  is  highly  constricted, 
forming  here  the  so-called  neck  of  the  tubule.  It  then  pursues  a  ser[)entine  course, 
this  entire  segment  of  it  being  known  as  the  first  or  distal  convoluted  tubule.  Then 
follows  a  narrow,  straight  portion  which  actually  enters  the  medulla  but  soon  recurs 
as  a  straight  segment  parallel  to  the  former.  These  constitute  the  descending  and 
ascending  limbs  of  the  U-shaped  loop  of  Henle.  Having  reentered  the  cortex,  the 
tubule  again  pursues  a  wavy  course  and  forms  the  second  or  proximal  convoluted 
tubule.      It  now  unites  with  others  of  the  same  kind  into  smaller  collecting  channels 


1066 


EXCRETION 


and  these  in  turn  into  larger  ones  until  about  a  dozen  conical  bundles  have  been 
formed,  each  of  which  constitutes  what  is  known  as  a  pyramid.  The  pointed  ex- 
tremity or  apex  of  each  p\Taraid  projects  well  into  the  pelvic  ca%'ity,  subdividing 
the  latter  into  a  number  of  recesses.  The  peh-is  is  in  free  communication  with  the 
ureter  of  which  it  really  forms  its  funnel-shaped  upper  expanse. 

The  flattened  epithelium  of  Bowman's 
capsule  is  reflected  over  the  tuft  of  capil- 
laries. In  the  distal  convoluted  tube, 
however,  the  lining  consists  of  high  and 
markedly  granular  cells  which  exhibit  a 
peculiar  brush-hke  ouiei  margin  and  vesic- 
ular formations.  In  the  descending  limb 
of  the  loop  of  Henle,  the  cells  are  flat  and 
clear,  while  those  of  the  ascending  limb 
are  again  higher  and  striated.  These 
changes  in  the  character  of  this  epithe- 
lium are  responsible  for  the  relative  nar- 
rowness of  the  lumen  of  the  ascending 
limb.  The  cells  of  the  proximal  con- 
voluted tubule  again  present  a  decided 
fibrillated  appearance.  Those  of  the 
collecting  channels  are  cuboidal  or  colum- 
nar in  shape  and  quite  clear. 

The  arterial  supply  of  the  kidney  is 
derived  from  the  renal  arterj'-.  Its  two 
terminal  branches  break  up  into  smaller 
ones  which  pass  at  first  directly  outward 
but  bend  at  almost  right  angles  as  soon  as 
they  have  reached  the  junction  between 
the  medulla  and  cortex.  From  these 
arched  transverse  vessels  arise  the  inter- 
lobular arteries  which  are  directed  straight 
toward  the  surface  of  the  organ  and  give 
off  here  and  there  transverse  branches 
which  finally  form  the  tufts  of  capillaries, 
pre\"iously  described  as  the  Malpighian 
corpuscles.  Each  glomerulus,  therefore, 
consists  of  an  afferent  vessel  representing 
one  of  these  branches,  and  a  much  nar- 
rower efferent  vessel  which,  after  leav- 
ing this  structure,  ramifies  extensively 
between  the  different  convoluted  tubules, 
rhis  capillars'  network  then  gives  rise  to 
the  interloHular  veins  and  these  in  turn  to 
the  renal  vein.  The  medulla  derives  its 
blood-supply  from  straight  arterioles 
which  arise  from  the  transverse  arterial 
arches.  These  constitute  the  arterial 
rectse. 

The  nerves  innervating  the  kidney  are 
derived  from  the  suprarenal  plexus  and 
follow  the  highway  of  the  arterv-  around 
which  they  form  a  rather  close  network.  This  plexus  is  known  as  the  renal 
plexus.  It  contains  afferent  and  efferent  fibers  which  are  chiefly  concerned  with 
the  acti%'ity  of  the  blood-vessels,  although  it  has  been  claimed  that  they  are  also 
secretomotor  in  their  function.  Preganglionically  these  fibers  are  contained  in 
the  greater  and  lesser  splanchnic  nerves. 


Fig.  524. — Dl\gr.\milvtic  Rzprzsex- 

TATIOX  OF  THE  BlOOD-SUPPLT  AXD  CoCRSE 
OF  THE  UrENIFEROUS  TuBrLE. 

J ,  Interlobular  blood-vessels  derived 
from  arches  between  corte.x  and  medulla; 
G,  glomenili;  C,  distal  convoluted  tubule; 
D  and  A,  descending  and  ascending 
limbs  of  the  loop  of  Henle;  CT,  collect- 
ing tubule;  P,  papilla  and  pelvis  of  the 
kidney. 


THE    SECRETION    OF    I'RINE  1067 

Theories  of  Urinary  Secretion. — The  kidney  is  the  most  important 
excretory  <)rji;an  of  tlie  body.  Its  function  is  to  separate  the  constitu- 
ents of  the  urine  from  tlu>  l)lo()d — its  watery  j)art  as  well  as  its  solids. 
Upon  it,  in  particular,  rests  the  maintenance  of  the  composition  of  the 
body-fluids;  and  hence,  it  must  keep  up  an  ahnost  continuous  activity 
which  cannot  be  compensated  for  by  any  other  or^an.  Thus,  it  is  a 
well-known  fact  that  the  removal  of  both  kidneys  is  fatal,  owing;  to 
the  accumulation  in  the  blood  of  the  end-products  of  protein  metabo- 
lism. Tiie  same  result  follows  the  ligation  of  both  renal  arteries, 
but  the  extirpation  of  only  one  organ  usually  produces  no  untoward 
effects,  because  the  opposite  organ  then  enlarges  and  accomplishes 
the  work  previously  performed  by  the  two  organs  together. 

The  modern  views  regarding  the  manner  in  which  the  renal  tubules 
perform  their  work,  is  based  upon  the  older  theories  of  Ludwig^  and 
Heidenhain.2  The  former  embodies  the  simple  physical  principles  of 
filtration  and  diffusion  and  the  latter,  these  principles  in  conjunction 
with  a  secretory  activity  on  the  part  of  the  lining  cells  of  tlie  tubules. 
The  filtration  theory  of  Ludwig  holds  that  the  glomerulus  plays  the 
part  of  a  filter,  giving  rise  to  a  quantitatively  and  qualitatively  com- 
plete urine  under  the  pressure  of  the  blood.  This  structure,  therefore, 
constitutes  the  most  important  segment  of  the  urinary  tubule,  while 
the  others  fulfill  merely  the  function  of  a  conducting  channel.  In 
substantiating  this  view,  Ludwig  laid  particular  stress  upon  the  struc- 
tural peculiarities  of  the  glomerulus,  emphasizing  the  fact  that  it 
consists  of  a  coil  of  capillaries  which  are  suspended  in  a  double-walled 
capsule.  Moreover,  the  narrowness  of  the  efferent  vessel  tends  to 
augment  the  lateral  pressure  and  to  diminish  the  velocity  of  the  blopd- 
flow.  As  far  as  the  pressures  are  concerned,  it  will  be  noted  that  a 
capillary  blood  pressure  of  40  to  60  mm.  Hg.  is  in  this  instance  con- 
trasted against  a  pressure  of  about  zero,  thus  affording  most  favorable 
conditions  for  a  passive  transfer  of  the  constituents  of  the  blood  into 
the  capsule  of  Bowman.  In  the  tubule  this  process  is  then  augmented 
by  an  endosmosis  between  the  concentrated  blood  and  the  watery 
urine  which  leads  to  a  passage  of  the  molecules  of  water  from  the  urine 
into  the  blood  until  the  former  has  acquired  its  normal  consistency. 
This  process  of  reabsorption  of  water  from  the  urine  Ludwig  conceived 
as  purely  physical  diffusion,  although  he  clearly  recognized  the  fact 
that  this  process  may  undergo  decided  changes  in  consequence  of  the 
administration  of  diuretics,  such  as  urea  and  sodium  chlorid. 

In  ]842  Bowman^  expressed  the  idea  that  the  glomerulus  serves 
merely  as  the  seat  of  the  secretion  of  the  watery  part  of  the  urine, 
whereas  its  solid  constituents  are  formed  in  the  tubule  itself.  In 
analogy  with  his  work  upon  other  glands,  Heidenhain  then  promulgated 
the  theory  that  the  urine  is  not  produced  solely  by  filtration  and 

1  Wagner's  Handworterb.  der  Physiol.,  ii,  1844,  628. 

2  Hermann's  Handb.  der  Physiol.,  v,  1883,  279. 

3  Phil,  transact.,  London,  i,  1842,  57. 


1068  EXCRETION 

osmosis,  but  is  materially  modified  by  the  activity  of  the  cells  lining 
the  convoluted  tubule.  It  is  assumed  that  the  glomerulus  furnishes 
the  water  and  inorganic  salts,  while  the  distal  convoluted  tubule 
produces  the  specific  organic  constituents,  together  with  an  inconsider- 
able quantity  of  water.  Thus,  the  character  of  this  secretion  depends 
in  reality  upon  the  activity  of  both  groups  of  cells  and  varies  with  the 
differences  in  the  composition  of  the  blood,  the  blood  pressure,  and  the 
velocity  of  the  capillary  blood-stream.  Th  ^s  rather  schematic  presenta- 
tion of  these  two  theories,  however,  should  not  convey  the  idea  that 
they  are  directly  opposed  to  one  another.  They  are  not,  because 
Heidenhain  does  not  deny  the  occurrence  of  filtration,  but  merely 
amplifies  this  process  by  the  secretory  activity  of  the  cells. 

Facts  Contradicting  the  Pure  Mechanical  Theory. — The  kidney 
is  one  of  the  most  vascular  organs  in  our  body,  receiving  about  150 
c.c.  of  blood  per  minute  for  each  100  grm.  of  substance;  moreover, 
its  blood-supply  is  accurately  controlled  by  a  vasomotor  mechanism 
contained  in  the  renal  and  suprarenal  plexuses.^  The  division  of  these 
fibers  gives  rise  to  a  relaxation  and  injection  of  the  blood-vessels  of 
this  organ,  this  change  being  associated  as  a  rule  with  a  copious  flow 
of  urine  and  a  slight  albuminuria.  It  is  also  a  well-established  fact  that 
urinary  secretion  is  closely  dependent  upon  the  blood  pressure,  because 
a  fall  in  the  latter  is  usually  followed  by  a  diminution  in  the  quantity 
of  the  urine,  and  vice  versa.  While  this  relationship  is  entirely  in 
accord  with  filtration,  it  can  easily  be  shown  that  pressure  is  not  the 
only  factor  here  at  work,  because  if  the  renal  vein  is  temporarily  ob- 
structed, a  procedure  which  must  necessarily  raise  the  intraglomerular 
pressure,  the  flow  of  urine  stops  altogether.  In  a  similar  way  it  has  been 
shown  that  a  partial  obstruction  of  the  venous  return  produces  only  a 
slight  diminution  in  the  rate  of  flow,  which  may  immediately  be  in- 
creased by  the  administration  of  a  diuretic.  This  latter  fact  is  of 
importance,  because  Sollmann's  experunents  upon  perfused  excised 
kidneys  have  shown  that  the  stoppage  of  the  flow  of  urine  following 
the  ligation  of  the  renal  vein,  may  be  caused  by  a  mechanical  obstruc- 
tion of  the  uriniferous  tubules  caused  by  the  distention  of  the  entire 
organ.  A  dissociation  between  the  renal  blood-supply  and  the  flow  of 
urine  may  also  be  effected  by  the  temporary  hgation  of  the  renal 
artery,  or  by  the  stimulation  of  the  vagus  nerve. ^  Almost  directly 
thereafter  the  flow  of  urine  ceases,  as  might  be  expected,  but  the  flow 
does  not  regain  its  former  value  immediately  upon  the  reestablishment 
of  normal  circulatory  conditions,  but  in  many  instances  only  after  an 
interval  of  from  30  to  60  minutes.  Consequently,  while  it  may  be 
granted  that  the  function  of  the  kidney,  like  that  of  other  organs, 
is  closely  dependent  upon  the  blood-supply,  it  is  easily  apparent 
that  some  outside  factor  is  here  at  work.     In  this  connection,  brief 

1  Bradford,  Jour,  of  Physiol.,  x,  1889,  358,  Asher  and  Pearce,  Zeitschr.  fur 
Biol.,  Ixiii,  1913,  83,  and  Burton-Opitz,  Jour.  Exp.  Med.,  xl,  1916,  437. 
-  Richards  and  Plaut,  Am.  Jour,  of  Physiol.,  xlii,  1917,  592. 


THE    SECRETION    OF    URINE  1069 

reference  should  also  be  made  to  the  action  of  adrenalin  which 
stops  the  secretion  of  urine  in  spite  of  the  fact  that  it  heightens  the 
blood  pressure.  This  discrepancy,  however,  is  only  an  appanmt  one, 
because  upon  its  entrance  into  the  kidneys,  this  agent  constricts  the 
local  blood-vessels  and  j^ives  rise  to  an  anemia  which  effectively  blocks 
the  activity  of  these  cells. 

Secondly,  it  might  be  mentioned  that  a  certain  secretory  resistance 
does  not  retard  the  function  of  the  renal  cells  but  actually  stimulates  it. 
While  it  is  true  that  urine  is  formed  under  a  glomerular  pressure  of 
from  40  to  60  mm.  Hg  and  a  ureter  pressure  of  about  zero,  the  latter 
may  be  heightened  considerably  before  the  cells  actually  cease  their 
function.  The  upper  limit  is  reached  at  about  60  to  80  mm.  Hg,  i.e., 
at  a  pressure  less  than  half  of  that  necessary  to  stop  the  secretion  of 
saliva.  The  reason  for  their  inability  to  raise  the  urinary  pressure 
more  decidedly  above  that  prevailing  in  the  capillaries,  is  due  in 
largest  part  to  the  early  occurrence  of  hydremia  which  indicates  that 
the  watery  constituents  of  the  urine  escape  into  the  interstitial  spaces 
and  are  reabsorbed.  Slight  increases  of  the  urinary  pressure,  on  the 
other  hand,  invariably'  augment  the  activity  of  these  cells. 

Thirdly,  mention  should  be  made  of  those  experiments  which 
jointly  establish  the  fact  that  the  epithelial  lining  of  the  urinary  tubules 
possesses  true  secretory  properties.  Heideniiain  first  attempted  to 
prove  this  positively  by  injecting  coloring  material  into  the  blood-stream 
of  rabbits  and  demonstrating  its  presence  in  the  cells  of  the  urinary 
tubule  by  histological  means.  In  order  to  eliminate  the  factor  of 
pressure  as  much  as  possible,  the  spinal  cord  was  cut  previous  to  the 
injection.  The  vascular  relaxation  then  ensuing  gave  rise  to  so  low 
a  blood  presssure  that  practical^  no  fluid  came  down  the  tubules. 
In  all  these  cases,  the  indigo-carmine  appeared  in  the  form  of  blue 
granules  within  the  cytoplasm  of  the  rodded  epithelium,  lining  the  con- 
voluted tubules  and  ascending  limb  of  the  loop  of  Henle,  but  not  in 
the  cells  of  the  glomeruli.  In  fact,  some  of  these  granules  could  also 
be  detected  in  the  lumen  of  the  urinary  tubule  This  was  invariably 
the  case  in  all  those  animals  whose  spinal  cord  had  not  been  divided 
before  the  injection.  Evidently,  the  retention  of  the  vascular  tonus 
of  the  kidney  tends  to  wash  these  granules  rapidly  out  of  the  cells 
into  the  secretory  duct. 

More  recently  Schaffer^  has  confirmed  these  results  by  means  of 
leuco-indigo-carmine,  a  colorless  reduction  derivative  of  indigo-car- 
mine. This  pigment  remained  colorless  in  the  cells  themselves,  but 
appeared  in  its  oxidized  (blue)  form  in  the  lumen  of  the  tubule.  It 
could  not  be  detected  in  the  capsule  of  Bowman.  Heidenhain  has  also 
shown  that  urate  of  soda  is  excreted  by  the  lining  cells  of  the  tubules. 
In  attempting  to  prove  that  the  glomerulus  acts  independently  of  the 
convoluted   tubule,   Lindemann-  sought   to  isolate  this  structure  by 

1  Am.  Jour,  of  Physiol.,  xxii,  1908,  323. 

2  Zeitschr.  fiir  Biol.,  xlii,  1902,  161. 


1070 


EXCRETION 


injecting  oil  into  the  circulation,  but  since  oil  embolisms  were  then  also 
found  in  the  blood-vessels  of  the  tubules,  this  method  yielded  no  positive 
results,  although  it  was  evident  that  the  tubular  vessels  ridded  them- 
selves of  these  embolisms  much  sooner  than  the  glomerular  vessels. 
Indigo-carmine  injcctctl  at  this  time  found  its  way  in  increasingly  small 
quantities  into  the  urine,  indicating  thereby  a  gradual  opening  up  of 
the  cells  lining  the  convoluted  tubules.  The  opposite  condition  may 
be  produced  in  rabbits  by  means  of  sodium  tartrate  which  substance 
gives  rise  to  an  inflammation  or  nephritis  of  the  tubule.^  If  a  solution 
of  sodium  chlorid  and  urea  is  then  injected 
into  the  circulation,  the  chlorin  enters  the 
urine  but  not  the  urea.  Obviously,  the  urea 
is  ordinarily  secreted  by  the  lining  cells  of  the 
tubule  and  not  by  those  of  the  glomerulus. 

Fourthly,  the  secretory  character  of  the 
tubular  epithelium  may  be  established  as 
follows:  In  the  frog  it  is  possible  to  render 
either  the  glomerular  or  the  tubular  segment 
of  the  urinary  tubule  bloodless,  because  the 
kidney  of  this  animal  receives  a  double  blood- 
supply.  The  one  from  the  renal  artery  nour- 
ishes the  glomerulus  and  the  one  from  the 
renal  portal  vein,  the  tubule.  Nussbaum^ 
has  shown  that  the  ligation  of  the  renal 
artery  greatly  diminishes  the  flow  of  urine. 
If  urea  is  now  injected  into  the  dorsal  lymph 
sac  of  this  animal,  a  very  considerable  amount 
of  this  substance  may  be  removed  from  the 
urine.  Obviously,  therefore,  the  urea  must 
have  found  its  way  through  the  cells  of  the 
tubules.  The  successful  outcome  of  this  ex- 
periment requires  a  constant  supply  of  oxygen 
in  order  to  retain  these  cells  in  a  proper  con- 
dition of  activity.  This  end  can  be  accom- 
plished by  placing  the  frog  in  an  atmosphere  of  oxygen.  Contrariwise, 
sugar,  peptone  and  egg-albumin,  when  injected  into  the  blood-stream,  do 
not  enter  the  urine  under  these  circumstances.  These  results  have  in 
the  main  been  confirmed  by  Beddard.^  In  addition,  it  has  been  shown 
that  the  cells  of  the  convoluted  tubule  eventually  degenerate  when 
supplied  only  with  renal-portal  blood,  because  this  blood  is  deficient 
in  oxygen.  The  stimulating  action  of  this  gas  upon  the  secretory 
power  of  the  renal  cells  is  also  indicated  by  the  experiments  of  Collis,^ 
which    show    that   the    perfusion    of    the    frog's    kidney    with    non- 

1  Underhill,   Wells  and  Goldschmidt,   Jour,   of  Exp.   Med.,  xviii,    1913,  347. 

2  Von  Furth,  Ergebn.  der  Physiol.,  1902,  395. 

3  Jour,  of  Physiol.,  xxviii,  1902,  20. 
^  Ibid.,  xxxvii,  1908,  8. 


Fig.  525. — Section 
through  the  convoluted 
Tubule  (Frog)  after  In- 
jection OF  TOLUIDIN. 

L,  Lumen  of  tubule;  C, 
blood  capillary.  The  lining 
cells  show  blue  pigment  and 
vesicles. 


TIIH    SECRETION    OF    URINE  1071 

oxygenated  saline  solution  •irc-itly  (liiiiiiiislics  llic  flow  of  urine. 
Contrariwise,  the  perfusion  of  lliisor^an  with  oxygenated  salt  solution 
increases  its  quantity. 

Fifthly,  attention  should  he  called  to  the  fact  that  the  cells  lining 
the  distal  urinary  tubule,  poss(>ss  all  the  essentials  of  secretory  cells. 
Thus,  vesicles  may  be  seen  to  form  within  their  cytoplasm,  the  con- 
tents of  which  are  later  on  discharged  into  the  lumen  of  the  tubule.* 
Besides,  Bowman  has  observed  crystals  of  uric  acid  within  th(>  ccills 
of  the  convoluted  tubules  of  birds.  Lastly,  it  is  a  well-known  fact 
that  the  secretion  of  urine  may  be  stimulated  by  means  of  various 
agents  to  which  the  name  of  diuretics  has  been  given,  and  which  in 
accordance  with  their  stimulating  action  upon  the  cells  themselves, 
may  be  placed  in  the  same  class  with  the  lymphagogu(\s,  cholagogues 
and  lactagogues.  Their  action  may  be  tested  most  advantageously  by 
perfusing  the  renal  portal  system  of  the  frog  with  oxygenated  salt 
solution  to  which  either  caffeine,  urea,  phloridzin,  or  sodium  sulphate 
has  been  added.  All  these  agents  incite  a  copious  secretion  of  urine 
as  well  as  a  very  striking  increase  in  the  oxygen  consumption  of  this 
organ.  Very  similar  results  may  be  obtained  in  mammals,  but  it  is 
to  be  noted  that  the  urine  secreted  under  the  influence  of  these  secreto- 
gogues, is  not  at  all  like  the  blood  plasma  in  its  composition  and  also 
varies  with  the  character  of  the  diuretic  employed.  The  vital  activity 
of  the  renal  cells  is  elucidated  further  by  the  fact  that  the  sugar 
and  proteins  of  the  blood  are  normally  retained  in  the  body,  whereas 
peptone  and  egg  albumin,  when  injected  into  the  circulation,  are 
eliminated  almost  immediately.  Moreover,  the  kidney  possesses 
the  power  of  abstracting  urea  from  the  blood,  but  does  not  excrete 
significant  amounts  of  sugar,  and  this  in  spite  of  the  fact  that  the  latter 
substance  is  present  in  much  larger  quantities  than  the  former. 

Absorption  from  the  Tubules. — While  the  preceding  experiments 
fully  disprove  the  pure  filtration  theory  of  urinary  secretion,  there  is 
still  another  point  embodied  in  Ludwig's  theory  which  has  given  rise 
to  much  discussion.  Reference  is  now  had  to  the  absorption  of  water 
from  the  urinary  tubule  to  render  the  urine  more  concentrated  than 
when  first  secreted.  This  reabsorption,  it  is  claimed  by  Ludwig,  is 
effected  through  the  blood  as  well  as  through  the  lymph.  In  the  first 
place,  it  must  be  admitted  that  the  constituents  of  the  urine  may  be 
made  to  pass  in  the  reverse  direction,  as  can  be  done  by  blocking  the 
ureter  and  allowing  the  pressure  in  the  tubules  to  rise  well  above  that 
prevailing  in  the  renal  capillaries.  Moreover,  when  substances, 
such  as  potassium  iodid,  are  at  this  time  injected  into  the  pelvis  of 
the  kidney,  they  soon  find  their  way  into  the  blood  where  they  may 
be  recognized  chemically.     The  only  question  to  be  decided  is  whether 

1  Gurwitch,  Pfluger's  Archiv,  xci,  1902,  71;  Courmont  and  Andre,  Jour,  de 
Physiol,  et  path,  gen.,  vii,  1905,  255;  and  Hliber  and  Konigsberg,  Pfluger's  Archiv, 
cviii,  1905,  323. 


1072  EXCRETION 

this  process  as  outlined  by  Liidwig  and  more  recently  by  Cushny,* 
also  takes  place  under  normal  conditions.  In  general,  it  may  be  said 
that  this  point  has  not  been  satisfactorily  proven;  at  least,  the  evi- 
dence so  far  presented  does  not  point  toward  a  reabsorption  of  suffi- 
cient magnitude  to  account  for  the  complete  concentration  of  the 
freshly  formed  waterj^  urine. 

The  factor  of  reabsorption  has  been  emphasized  in  more  recent 
years  by  Brodie  and  Callis,^  and  especiall}^  by  Cushny.  Possibly  the 
strongest  point  against  this  contention  is  that  the  amount  of  water 
which  would  have  to  be  reabsorbed  from  the  uriniferous  tubules,  ap- 
proximates the  enormous  value  of  70  liters  per  day,  but  Cushnj^  believes 
that  this  is  not  a  convincing  criticism,  inasmuch  as  the  secretion 
for  each  tubule  would  even  then  be  only  about  0.014  c.c.  in  the  course 
of  one  hour.  Ribbert^  has  approached  this  problem  by  removing 
as  extensive  a  portion  of  the  tubules  as  possible,  the  contention  being 
that  if  reabsorption  actually  takes  place,  a  much  more  fluid  urine  should 
then  be  obtained.  Wliile  this  was  actuall}^  the  case,  these  results  and 
their  interpretation  in  favor  of  the  absorption  theory  have  been  ad- 
versely criticized  by  Boyd^  and  H.  Meyer.  ^  The  latter  in  particular 
lays  stress  upon  the  fact  that  the  character  of  the  urine  after  partial 
removal  of  the  medullary  substance  more  closely  approaches  that  of 
an  albumin-free  filtrate.  Furthermore,  Gurwitsch*'  has  pointed  out 
that  the  ligation  of  the  renal  portal  system  in  frogs  diminishes  the 
quantity  of  the  urine,  as  compared  with  that  secreted  by  the  normal 
organ  on  the  opposite  side.  Consequently,  if  the  tubules  actually  did 
absorb  a  large  portion  of  the  water  of  the  newly  formed  urine,  the 
abolition  of  their  function  should  really  give  rise  to  a  more  copious 
and  watery  urine.  As  has  just  been  stated,  this  is  not  the  case.  In 
addition,  it  must,  of  course,  be  evident  that  a  process  of  secretion 
invariabh^  necessitates  two  solutions,  namely,  the  blood  and  the  secre- 
tory product  separated  by  an  animal  membrane,  and  ]\Iagnus,  SoU- 
mann  and  others  have  shown  repeatedly  that  any  interchange  between 
these  cannot  be  effected  without  the  participation  of  the  dissolved 
substances.  For  this  reason,  a  slight  reabsorption  may  be  essential 
at  times  to  equalize  osmotic  conditions,  but  not  at  all  for  the  singular 
purpose  of  removing  only  the  water. 

"Modem"  Theory  of  the  Secretion  of  Urine. — The  so-called 
"modern"  theory  of  Cushny  embodies  the  principles  of  urinar}^  secre- 
tion as  outlined  by  Ludwig,  and  in  addition,  a  reabsorption  of  the  water 
and  inorganic  constituents  of  the  newly  formed  urine.  The  latter 
is  effected  by  a  vital  activity  on  the  part  of  the  epithelium  of  the  tub- 

^  The  Secretion  of  Urine,  London,  1917;  also:  Addis  and  Sheokv,  Am.  Jour,  of 
Physiol.,  xliii,  1917,  363. 

2  Jour,  of  Physiol.,  xxxiv,  1906,  224. 

3  Virchow's  Archiv,  xciii,  1883.  169. 
^  Jour,  of  Physiol.,  xxviii,  1902,  76. 
5  Marb.  Sitzunssber.,  1902. 

"  Pfiuger's  Archiv,  xci,  1902,  71. 


THE    SECRETION    OF   URINE  1073 

ulos.  It  is  held  that  a  large  quantity  of  plasma  is  filtered  through  the 
gloiiKM-ular  vessels  under  the  pressure  of  tlie  blood  anrl  under  exclusion 
of  the  colloidal  proteins.  The  non-colloidal  material  being  allowed  to 
pass,  owing  to  the  permeability  of  the  vessel-wall,  imparts  to  the  urine 
a  concentration  approximately  e(iual  to  that  of  the  blood.  Corise- 
(piently,  the  blood  leaving  the  glomeruli,  may  be  compared  to  a  con- 
centrated colloid  solution  which  requires  salts  and  water  to  reconvert 
it  into  its  original  form.  This  end  the  blood  attains  as  it  traverses 
the  tubule  by  absorbing  the  constituents  recpiired  by  it  from  the 
glomerular  filtrate.  Those  substances  which  the  plasma  must  again 
obtain,  are  called  threshold  substances,  while  those  which  it  does  not 
need  again,  are  designated  as  non-threshold  substances.  The  latter 
remain  in  the  urine  to  be  excreted.  Thus,  urea  must  leave  the  body 
as  long  as  any  of  it  is  present  in  the  blood,  whereas  the  urinary  sugar 
must  again  pass  into  the  blood,  provided  its  concentration  remains 
below  the  physiological  limit. 

This  theory  may  well  be  employed  to  explain  several  perplexing 
points  regarding  the  pathology  of  the  kidney,  particularly  such  as 
concern  diuresis,  albuminuria  and  the  phenomena  associated  with  the 
stagnation  of  the  urine  in  consequence  of  urethral  obstructions.  In 
spite  of  this  fact,  however,  it  cannot  be  said  that  it  rises  above  the 
dignity  of  a  mere  working  hypothesis,  because  in  view  of  the  uncertain 
and  contradictory  character  of  the  evidence  presented  in  its  favor, 
it  seems  risky  to  accept  it  as  a  truity.  None  seems  sufficiently  definite 
to  allow  of  no  other  and,  possibly,  more  correct  interpretation.  It 
appears,,  therefore,  that  the  student  who  accepts  Heidenhain's  theory 
which  does  not  wholly  exclude  the  factor  of  glomerular  filtration,  can- 
not be  considered  as  less  "modern"  than  the  one  who  adheres  to  the 
absorption-hypothesis.  Thus,  it  may  be  said  that  water  and  salts, 
and  even  such  substances  as  sugar,  egg-albumin,  peptone  and  hemo- 
globin when  injected  into  the  blood-stream,  are  mainly  excreted  by 
the  glomeruli,  whereas  urea,  uric  acid,  and  the  other  organic  constitu- 
ents, together  with  small  amounts  of  water  and  salts,  are  excreted 
by  the  epithelium  of  the  uriniferous  tubule.  Neither  process  is  accom- 
plished by  filtration  alone,  but  embraces  a  definite  vital  element 
consisting  of  unknown  physicochemical  factors  resident  in  the  renal 
cells.  Both  processes  are  closely  dependent  upon  the  pressure  and 
velocity  of  the  renal  blood  flow.  In  this  connection,  it  should  also 
be  mentioned  that  the  existence  of  separate  secretory  nerves  to  the 
kidney  has  not  been  proved, '^  although  it  must  be  granted  that  the 
stimulation  of  the  fibers  constituting  the  renal  plexus,  profoundly 
affects  the  quantity  and  quahty  of  the  urine.  These  results,  however, 
may  be  due  wholly  to  vasomotor  influences. 

Diuresis, — The  diuretics  produce  their  characteristic  effect  in  two 
ways,  namely,  by  augmenting  the  secretory  pressure  and  concentra- 

^  Asher  and  Pearce,  Zeitschr.  fiir  Biol.,  Ixiii,  1913,  83;  and  Pearce  and  Carter, 
Am.  Jour,  of  Physiol.,  xxxviii,  1915,  350. 

68 


1074  EXCRETION 

tion  of  the  blood,  or  by  furthering  the  activity  of  the  renal  cells.  Con- 
sequently, either  the  glomerulus  or  the  tubule  may  be  involved  in  this 
process.  Thus,  we  might  say  that  digitalis  enhances  the  circulatory 
conditions,  because  it  stimulates  the  cardiac  musculature  and  raises 
the  tonicity  of  the  vascular  channels.  Caffeine  possesses  a  similar 
action.^  It  is  evident,  however,  that  a  mere  increase  in  the  vascularity 
or  a  passive  injection  of  the  renal  capillaries  does  not  give  rise  to  a  flow 
of  urine.  Another  way  in  which  the  secretory  conditions  might  be 
altered,  is  to  change  the  osmotic  pressure  of  the  blood.  For  example, 
if  a  hypertonic  solution  of  sodium  chlorid  is  injected  into  the  circula- 
tory system,  the  osmotic  pressure  of  the  blood  is  increased,  and  fluid 
is  drawn  into  the  vascular  channels  from  the  lymphatics  until 
it  acquires  a  lower  osmotic  pressure. ^  This  condition  is  called 
hydremic  plethora.  It  follows  then  that  the  renal  blood  flow  is  more 
rapid  and  forceful,  a  change  which  greatly  favors  the  transudation 
of  the  excess  of  fluid  through  the  renal  capillaries.  The  same  effect 
may  be  produced  intentionally  by  the  ingestion  of  large  quantities 
of  water  or  by  means  of  dialyzable  substances,  such  as  sodium  sul- 
phate, sodium  or  potassium  bicarbonate,  the  acetate,  citrate  or  bitar- 
trate  of  potassium,  liquor  ammonii  acetatis,  liquor  ferri  et  ammonii 
acetatis,  urea,  and  dextrose.  The  most  efficient  of  these  are  the 
bicarbonates  and  potassium  acetate.  Urea  and  dextrose  may  act 
chiefly  as  direct  stimulants  to  the  renal  cells,  but  also,  in  a  measure, 
by  changing  the  osmotic  conditions.  Pituitary  extract  seems  to 
possess  a  direct  action  upon  the  cells  although  its  action  upon  the 
circulatory  system  cannot  be  excluded. 

A  more  detailed  explanation  of  diuresis  cannot  be  given  unless  re- 
sort is  taken  to  the  well-conceived  but  still  hypothetical  absorption 
"theory."  If  the  polyuria  of  diabetes  mellitus  is  taken  as  an  example, 
it  might  be  said  that  the  kidney  is  quite  unable  to  concentrate  the 
urine  against  the  concentrated  sugar-urine  in  the  tubules.  In  accord- 
ance with  the  preceding  discussion,  this  would  imply  that  sugar  be- 
comes a  "non-threshold"  substance,  owing  to  the  presence  of  sugar 
in  the  blood  in  amounts  greater  than  the  optimum. 

Albuminuria.— While  the  proteins  of  the  blood  do  not  enter  the 
blood  under  normal  conditions,  their  escape  cannot  be  prevented  if 
the  permeability  of  the  glomerulus  is  increased.  A  condition  of  this 
kind  develops  rn  acute  nephritis  and  cardiac  failure.  The  quantity 
of  the  urine  is  then  usually  diminished,  but  the  question  of  whether 
this  disease  remains  confined  to  the  glomeruli  or  also  involves  the 
tubules,  cannot  be  decided  with  certainty.  Theoretically,  however, 
we  might  expect  to  obtain  a  glomerular  as  well  as  a  tubular  nephritis. 
In  the  chronic  type  of  this  disease  the  urine  retains  a  low  specific 
gravity  and  viscosity^  and,  using  the  absorption  hypothesis  as  a  basis, 

1  Lowi,  Arch,  fur  exp.  Path,  und  Pharm.,  liii,  1905,  i. 

2  Gottlieb  and  Magnus,  ibid.,  xlv,  1901,  223. 

3  Burton-Opitz  and  Dinegar,  Am.  Jour,  of  Physiol.,  xlvii,  1918,  220. 


THE    EXPULSION    OF   THE    URINE.       MICTURITION  1075 

it  might  be  said  that  this  com Ut ion  is  depciulcnt  upon  an  impairment 
of  the  resorbing  mechanism. 

Let  us  also  remember  that  the  removal  of  one  kidney  is  not  followed 
by  any  untoward  results,  because  the  opposite  or^jan  th<^n  enlarges 
and  continues  to  do  the  work  previously  accomplished  by  th(!  two. 
The  extirpation  of  both  Icidneys,  however,  proves  fatal  invariably,  the 
animal  dying  a  few  days  later  of  uremic  poisoning.  The  same  re- 
sults follow  the  ligature  of  both  renal  arteries.'  While  the  conditions 
of  anasarca,  ascitis,  and  others,  woukl  furnish  many  points  of  physi- 
ological interest,  they  more  properly  belong  into  the  field  of  general 
pathology. 


CHAPTER  XC 
THE  EXPULSION  OF  THE  URINE.     MICTURITION 

The  Function  of  the  Ureter. — The  duct  of  each  kidney,  or  ureter, 
is  a  muscular  tube  measuring  about  30  to  45  cm.  in  length.  It  begins 
above  at  the  pelvis  and  terminates  below  in  the  wall  of  the  bladder. 
It  is  lined  by  mucous  membrane  and  consists  of  an  inner  circular  coat 
of  smooth  muscle  tissue  and  an  outer  coat  of  fibrous  tissue.  As  the 
small  globules  of  urine  escape  from  the  different  collecting  tubules, 
they  are  retained  at  first  in  the  pelvic  cavity  until  this  reservoir  has 
become  sufficiently  distended.  A  reflex  is  then  set  up  which  gives 
rise  to  peristaltic  waves  which  travel  slowly  in  the  direction  of  the 
bladder,  each  contraction  forcing  a  small  amount  of  urine  ahead  of  it. 
These  waves  recur  at  rather  regular  intervals  and  increase  in  frequency 
as  larger  amounts  of  urine  are  secreted.  Their  number  is  usually  3 
to  6  in  a  minute  and  their  rate  of  progression  2  to  3  cm.  in  a  second. ^ 

The  activity  of  the  ureter  is  controlled  by  nerve  fibers  derived  from 
the  renal  plexus  as  well  as  from  the  hypogastric  nerves.  Their  central 
segments,  however,  are  said  to  be  free  from  them,  although  ganglion 
cells  have  been  detected  throughout  their  entire  length.  In  accordance 
with  this  rather  deficient  nerve-supply,  Engelmann^  has  formulated 
the  theory  that  these  rhythmic  contractions  are  of  myogenic  origin. 
This  view  finds  additional  support  in  the  fact  that  even  excised  portions 
of  the  ureter  show  a  peristaltic  activity  which  may  be  greatly  increased 
by  immersing  them  in  warmed  saline  solution.  Equally  convincing 
data,  however,  might  be  submitted  in  favor  of  the  neurogenic  theory, 
and  hence,  no  definite  statements  can  be  made  at  this  time  regarding 

1  Pitcher,  Jour.  Biol.  Chem.,  xiv,  1913,  387. 

''■  Heidenhain,  Archiv  fiir  mikr.  Anat.,  1874;  and  Protopow,  Pfliiger's  Archiv, 
Ixvi,  1897. 

3  Pfliiger's  Archiv,  ii,  1869. 


1076  EXCRETION 

this  matter.  The  pelvic  segment  of  the  ureter  is  undoubtedly  well 
equipped  with  nerve  fibers  and  it  appears  that  this  portion  acts  as  the 
pace-maker  for  the  lower  segments.  Experimentally,  however,  it  is 
possible  to  evoke  peristalsis  in  any  part  of  this  organ.  Since  smooth 
muscle  tissue  is  seldom  richly  supplied  with  nerve  tissue,  the  relatively 
"nerve-free"  central  portion  might  normally  be  dependent  upon  in- 
fluences conveyed  to  it  from  the  pace-maker  through  the  agency  of 
the  aforesaid  ganglion  cells.  ^ 

The  Urinary  Bladder. — The  bladder  is  composed  of  a  mucous, 
submucous,  muscular  and  serous  layer.  Its  muscular  coat  contains 
an  outer  longitudinal,  a  middle  circular,  and  an  inner  anastomosing 
or  oblique  layer  of  fibers.  The  fibers  of  the  first  pass  in  an  almost 
direct  line  from  the  fundus  to  the  urethra,  where  some  of  them  become 
attached  to  the  pelvis  as  the  pubovesical  muscle.  Posteriorly,  the 
strands  end,  in  the  male,  in  the  prostate  and,  in  the  female,  in  the 
urethral-vaginal  septum.  The  median  coat  is  much  thicker  and  con- 
sists of  fibers  arranged  transversely  to  the  long  axis  of  the  organ.  At 
the  cervix,  this  layer  is  materially  strengthened,  forming  here  the  inter- 
nal sphincter  vesicse.  Farther  outward  and  enveloping  the  root  of 
the  urethra,  is  a  second  sphincter  which  is  composed  of  striated  muscle 
tissue,  and  is  usually  designated  as  the  external  sphincter  or  sphincter 
urethrae.  The  inner  coat  of  muscle  tissue  consists  of  obliquely  ar- 
ranged fibers  which  are  distributed  in  an  irregular  manner  and  per- 
meate the  different  layers. 

As  each  ureter  continues  to  empty  small  quantities  of  urine  into 
the  fundus  of  the  bladder,  its  walls  are  forced  outward  more  and  more 
until  they  have  attained  a  physiological  degree  of  distention.  A 
contraction  of  the  musculature  then  ensues  which  drives  the  urine 
through  the  relaxed  sphincters  to  the  outside.  Under  ordinary  con- 
ditions, therefore,  the  peristaltic  waves  of  the  ureters  need  not  over- 
come a  considerable  resistance  and  their  power  is  more  than  ample  to 
force  the  urine  into  the  fundus.  But  a  regurgitation  of  the  urine  into 
the  ureters  is  quite  impossible  even  during  the  interims,  because  the 
orifices  of  the  ureters  are  firmly  closed.  This  end  is  not  accomplished 
by  special  sphincters,  but  in  an  indirect  way  by  the  distention  of  the 
walls  of  the  bladder.  Inasmuch  as  the  ureters  perforate  the  latter  in 
an  obhque  direction  and  open  by  means  of  slit-like  orifices,  the  gradual 
filling  of  the  bladder  must  cause  the  lip-like  margins  of  these  openings 
and  neighboring  segments  of  the  ureters  to  become  firmly  approxi- 
mated. Consequently,  the  greater  the  internal  pressure,  the  more 
firmly  will  these  orifices  be  closed.  In  general,  therefore,  it  may  be 
said  that  three  factors  are  at  work  to  prevent  the  regurgitation  of 
the  urine,  namely,  gravity,  the  peristaltic  action  of  the  ureters,  and  the 
mechanical  closure  of  their  orifices  by  the  distention  of  the  walls  of 
the  bladder. 

The  foregoing  discussion  also  shows  that  the  high  pressures  which 
1  Lucas,  Am.  Jour,  qf  Physiol.,  xvii,  1906,  392. 


THE    EXPULSION    OF    THE    IHINK.       MKTrHITION  1077 

are  dovelopod  at  tiiiios  within  the  bhuklcr  durinji;  its  periods  of  con- 
traction, cannot  possibly  inlorfcre  with  th(!  vascular  supply  nor 
the  secretory  function  of  the  kidneys.'  Very  different  conditions, 
however,  arise  if  the  pressure  in  the  ureter  itself  is  raised  excessively, 
a  condition  commonly  associated  with  the  staM;nation  of  the  urine  in 
consequence  of  renal  calculi.  A  very  decided  reduction  in  the  blood 
flow  through  the  corresponding  kidney  then  results  which  cannot 
remain  without  effect  upon  its  secretion. 

Physiologically,  the  bladder  must  be  considered  as  a  hollow  muscu- 
lar organ,  the  contraction  of  which  places  its  contents  under  a  consider- 
able pressure. 2  Since  the  orifices  of  the  ureters  are  closed,  the  pressure 
so  developed  must  be  directed  toward  the  internal  and  external  sphinc- 
ters. The  resistance  of  the  latter,  however,  cannot  be  overcome  by 
pressure  alone,  and  hence,  the  voiding  of  urine  or  act  of  micturition 
must  also  necessitate  the  relaxation  of  these  bands  of  muscle  tissue, 
the  inner  one  by  reflex  action  and  the  outer  one  volitionally.  A  third 
factor  at  work  during  this  process  is  the  abdominal  press.  It  will  be 
remembered  that  the  latter  consists  in  an  inspiratory  action  which 
is  immediately  followed  by  a  closure  of  the  laryngeal  orifice  and  a  con- 
traction of  the  abdominal  muscles  and  diaphragm.  The  increase  in 
the  abdominal  pressure  produced  thereby  is  propagated  unto  the  pelvic 
organs  and  favors  micturition  as  well  as  defecation.  In  most  in- 
stances, however,  it  is  not  brought  into  play  until  the  final  stages  of 
these  acts. 

Under  ordinary  conditions,  micturition  does  not  result  until  the 
pressure  in  the  bladder  has  risen  to  about  150  mm.  H2O,  i.e.,  at  a  time 
when  this  organ  has  been  distended  sufficiently  to  contain  between 
230  and  2.50  c.c.  of  urine.  To  begin  with,  of  course,  the  pressure 
increases  very  slowly,  owing  to  the  constant  relaxation  of  the  walls  of 
the  bladder.  Eventually,  however,  as  the  tissues  have  about  attained 
their  maximal  degree  of  stretching,  the  pressure  rises  more  rapidly 
and  finally  evokes  a  series  of  slight  rhythmic  oscillations  which  are 
soon  succeeded  by  more  forcible  contractions.  But,  much  depends 
ujx)n  the  rapidity  with  which  the  bladder  is  being  filled,  because  a  slow 
influx  of  urine  enables  the  different  muscle  fibers  to  lengthen  more 
gradually,  while  a  more  rapid  influx  causes  them  to  react  antagonisti- 
cally by  tonic  or  rhythmic  contractions,  thereby  evoking  micturition 
much  sooner.  Furthermore,  since  the  external  sphincter  is  under  the 
control  of  the  wfll,  the  forceful  contraction  of  this  ring  of  muscle  tissue 
may  overcome  these  reflexes,  at  least  for  a  short  time.  When  aided 
by  the  abdominal  press,  a  pressure  of  2  m.  HoO  may  be  produced. 

The  Nervous  Control  of  the  Bladder. — The  reflex  center  for  mictu- 
rition is  situated  in  the  lumbosacral  segment  of  the  spinal  cord,  whence 
connections  are  formed  wnth  the  higher  centers.     In  this  way,  volition 

^  Burton-Opitz,  Pfliiger's  Archiv,  cxxiii,  19. 

^  Rehfisch,  Virchow's  Archiv,  xl,  1897,  ill;  also:  Mosso  and  Pellacani,  Arch, 
ital.  de  biol.,  i,  1882,  291. 


1078 


EXCKETION 


and  various  afferent  impulses  may  be  brought  to  bear  upon  this  reflex 
mechanism.  Thus,  we  have  previously  found  that  micturition  may 
also  be  evoked  by  associations  resulting  in  consequence  of  visual  and 
auditory  impressions,  such  as  the  sight  or  sound  of  running  water. 
Secondly,  the  action  of  the  simple  center  may  be  inhibited  or  accelerated 
by  volition.  In  the  latter  case,  however,  the  impulses  seem  to  be  con- 
centrated upon  the  sphincter  mechanism  and  upon  those  perineal  mus- 
cles which  normally  aid  in  the  closure  of  the  urethra.     Contrariwise, 


Bud.  tnes.  ganglion 


Sup.  nies.  nerves* 

Median  mes.  nerves. 
Inf.  mes.  nerves'- 


3rd  lumb.  vert 


-  -.flypogastric 
plexus 

-  --Sacrum 

-  •  •.Sciatic  n. 
Sacral  nerves 


Fig.  526. — Nerve  Supply  to  Bladder  of  Cat.      {Nawrocki  and  Skabitschewsky.) 

the  relaxation  of  these  sphincters  may  be  hastened  by  the  con- 
traction of  the  abdominal  muscles;  in  fact,  it  is  held  by  some  investi- 
gators that  even  the  involuntary  muscle  tissue  of  the  bladder  is  partially 
under  the  control  of  the  cortex  of  the  cerebrum.  This  view  is  based 
upon  the  fact  that  the  destruction  of  the  crus  cerebri  in  animals  whose 
abdomen  had  been  opened,  gives  rise  to  a  contraction  of  the  bladder. 
Since  the  local  mechanism  of  micturition  requires  efferent  impulses 
which,  on  the  one  hand,  lead  to  a  contraction  of  the  musculature  of 


THE    EXPULSION    OF   THE    URINE.       MICTURITION  1079 

the  bladder,  and,  on  the  other,  to  a  rehixatioii  of  the  sphincter,  two 
separate  nerve  paths  must  he  provided  for.  According  to  Langlcy 
and  Anderson,'  one  of  these  arises  in  the  four  upper  hnubar  nerves  and 
the  other,  in  the  second  and  tiiird  sacral  nerves  by  way  of  the  visceral 
nerves  of  the  pelvis,  the  nervi  erigentes.  The  former  eventually  termi- 
nate in  the  bilateral  inferior  mesenteric  ganj^lion,  whence  a  new  relay 
of  fibers  is  formed  which  extends  in  the  form  of  two  nerves,  the  hypo- 
gastric nei-ves,  into  the  pelvis  on  each  side  of  the  rectum.  They  termi- 
nate finally  at  the  base  of  the  bladder  in  an  extensive  ramification 
which  is  known  as  the  hypogastric  plexus.  From  here  these  fibers 
ascend  to  the  fundus  of  the  bladder.  The  second  S(!t  of  fibers  passes 
from  the  second  and  third  sacral  nerves  directly  to  the  hypogastric 
plexus,  and  hence,  they  do  not  first  enter  the  sympathetic  system. 
Their  relay  stations  lie  in  the  aforesaid  plexus  and  in  the  walls  of  the 
bladder  itself.  The  afferent  impulses  from  this  organ  select  chiefly 
these  visceral  fibers  of  the  pelvis  in  reaching  central  parts. ^ 

This  brief  enumeration  shows  that  the  hypogastric  plexus  is  sup- 
plied with  sympathetic  fibers  from  the  lumbar  cord  and  with  para- 
sympathetic fibers  from  the  sacral  cord.  As  far  as  the  individual 
action  of  these  fibers  is  concerned,  further  investigations  are  needed  to 
be  able  to  cite  definite  results.  All  physiologists,  however,  are  agreed 
that  the  excitation  of  the  sacral  fibers  on  either  side  produces  a  strong 
contraction  of  the  bladder,  leading  to  the  relaxation  of  the  sphincters 
and  the  discharge  of  the  urine.  But,  the  question  whether  these 
nerves  actually  contain  inhibitory  fibers  for  the  sphincters,  has  not  been 
definitely  settled.  Fagge,^  for  example,  claims  that  they  do  not  and 
that  the  relaxation  of  the  sphincters  takes  place  indirectly  in  conse- 
quence of  the  high  intravesical  pressure.  The  function  of  the  hypo- 
gastric nerves  has  not  been  clearly  established,  because  it  is  not  the 
same  in  all  animals.  In  the  dog,  their  stimulation  leads  to  a  strong 
contraction  of  the  musculature  around  the  base  of  the  bladder,  whereas 
in  the  cat  and  rabbit  this  procedure  gives  rise  to  an  inhibition.  It 
appears,  however,  that  they  are  never  without  motor  fibers  for  the 
sphincter  vesicae  and  the  constrictor  tissue  of  the  urethra. 

1  Jour,  of  Physiol.,  xix,  1895,  71;  also  Stewart,  Am.  Jour,  of  Physiol.,  xxx, 
1899,  i. 

2  Nawrocki  and  Skabitschevvsky,  Pfliiger's  Archiv,  xlix,  1891,  141. 
5  Jour,  of  Physiol.,  xxviii,  1902,  305. 


1080  EXCRETION 


CHAPTER  XCI 
THE  COMPOSITION  OF  THE  URINE 

General  Characteristics  of  Urine. ^ — The  urine  of  man  is  a  clear, 
fluorescent  fluid,  the  color  of  which  varies  from  hght  yellow  to  dark 
yellow  in  accordance  with  its  content  in  pigmentous  material.  The 
latter  consists  chiefly  of  urochrome,  which  is  composed  of  11.1  per  cent, 
of  nitrogen  and  5  per  cent,  of  sulphur,  and  is  in  all  probability  derived 
from  protein.  Urobilin,  another  pigment,  is  present  in  normal  urine 
in  only  very  small  quantities.  It  is  derived  from  the  coloring  mate- 
rial of  the  bile  which  is  converted  in  the  intestines  into  stercobilin. 
While  the  latter  leaves  the  body  principally  in  the  feces,  some  of  it 
is  reabsorbed  to  be  finally  excreted  in  the  urine.  Its  mother-sub- 
stance, known  as  urobilinogen,  is  present  in  somewhat  greater  quanti- 
ties and  is  easily  oxidized  into  urobilin  proper.  The  pink  coloring 
material  of  the  urates  is  uroerythrin.  A  trace  of  hem.atoporpJnjrin 
is  also  present  normally. 

The  odor  of  urine  depends  upon  the  quality  of  the  food  ingested. 
When  meat,  bread  and  butter  are  taken,  it  is  not  at  all  unpleasant. 
A  most  peculiar  odor  is  imparted  to  it  by  asparagus.  To  the  taste  urine 
is  bitter  and  salty.  The  quantity  of  urine  varies  considerably,  and  de- 
pends upon  the  intake  of  water  and  the  proportion  of  it  which  is  ex- 
creted through  other  channels,  such  as  the  intestines,  sweat  glands  and 
respiratory  passage.  Under  ordinary  conditions,  from  1400  to  1800 
c.c.  are  voided  in  the  course  of  twenty-four  hours,  the  smallest  portion 
of  this  amount  being  excreted  during  the  night.  If  a  reverse  relation- 
ship exists  so  that  the  person  must  micturate  during  the  night,  sus- 
picions of  renal  disease  should  be  aroused,  but  naturally,  only  if  moder- 
ate amounts  of  water  and  other  fluids  have  been  taken  on  the 
evening  preceding. 

The  specific  gravity  of  the  urine  varies  greatly  in  different  persons  as 
well  as  in  the  same  person  at  different  times  of  the  day.  The  chief 
factor  tending  to  vary  its  value  is  the  proportion  of  water  to  the  amount 
of  solids  ingested,  and  the  relationship  between  the  activity  of  the 
kidneys  and  that  of  the  other  excretory  channels.  Under  ordinary 
conditions,  values  between  1.015  and  1.025  are  encountered,  while 
a  constant  value  of  1.010  and  less  would  point  toward  the  presence 
of  hydruria,  and  one  of  1.030  and  over,  toward  diabetes.  Temporary 
variations  of  this  kind,  however,  are  common  and  may  easily  be  pro- 
duced by  an  intake  of  large  quantities  of  water  or  by  profuse  sweating. 

1  For  a  more  detailed  discussion  the  reader  is  referred  to  Mathew's  Biological 
Chemistry,  Hamburger's  Osm.  Druck  and  Jonenlehre,  and  Oppenheimer's  Handb. 
der  Biolog.  Chemie. 


THE    COMPOSITION    OF    THE    URINE  1081 

The  viscosity  of  wine  is  normally  1.2  as  great  as  that  of  distilled  water 
at  37°  C.  While  blood  freezes  at  -0.50°  C,  urine  freezes  at  -°1.0  to 
—  2.5°  C.  If  \(ny  dilute,  the  freezing  point  may  lie  at  0.075°  C,  and  if 
very  concentrated  at  —5°  C. 

The  reaction  of  the  urine  of  man  and  the  carnivora  is  acid  to  litmus 
and  phenolphthalein.  This  is  due  to  the  fact  that  neutral  constitu- 
ents of  the  food  are  eventually  transformed  into  acid  end-products,  the 
sulphur  of  the  proteins  giving  rise  to  sulphuric  acid,  and  the  phosphorus 
of  lecithin  to  phosphoric  acid.  An  ingestion  of  large  quantities  of 
vegetables  and  fruits,  however,  will  make  it  alkaline  and  turbid,  owing 
to  the  precipitation  of  earthy  phosphates.  In  the  herbivora,  the  urine 
is  alkaline,  because  their  food  embraces  fruits  and  vegetables  which 
contain  salts  of  dibasic  or  polybasic  acids,  such  as  acid  potassium 
malate,  citrate,  acetate  and  tartrate.  The  oxidation  of  these  bodies 
during  metabolism  gives  rise  to  carbonates.  Some  of  the  carbonic 
acid  leaves  the  body  through  the  lungs,  whereas  their  bases  are  excreted 
in  the  urine  as  alkaline  carbonates.  For  this  reason,  the  urine  of  these 
animals  frothes  on  addition  of  an  acid.  Furthermore,  if  these  animals 
are  starved,  their  urine  becomes  acid,  because  thc}^  then  live  upon  their 
tissues  and  are  converted,  so  to  speak,  into  carnivorous  animals.  This 
is  also  true  of  man,  because  the  withholding  of  fruits  and  vegetables 
removes  all  possibility  of  the  urine  becoming  alkaline.  In  disease, 
it  is  more  generally  acid,  this  change  being  due  in  most  instances  to  the 
restriction  of  the  diet.  With  the  increase  in  acidity,  the  excretion  of 
ammonia  is  usually  augmented. 

The  composition  of  the  urine  differs  somewhat  with  the  type  of 
food  ingested  and  the  quantity  of  water  eliminated  through  this  channel. 
In  general,  however,  it  may  be  said  to  contain  60  grm.  of  solids,  of 
which  25  grm.  are  in  the  form  of  inorganic  and  35  grm.  in  the  form 
of  organic  substances.  Thus,  an  adult  man  on  a  mixed  diet  j'ields 
about  1500  c.c.  of  urine  in  a  day  which  shows  the  following  compo- 
sition:^ 

Inorganic  substances  Organic  substances 

Sodium  chloric! 15.0  grams  Urea 30 . 0  grams 

Sulphuric  acid 2.5  grams  Uric  acid 0.7  grams 

Phosphoric  acid 2.5  grams  Creatinine 1.0  grams 

Potassium 3.3  grams  Hippuric  acid 0.7  grams 

Ammonia 0.7  gram  Other  constituents 2.6  grams 

Magnesia 0.5  gram 

Lime 0.3  gram 

Other  constituents 0.2  gram 

THE  INORGANIC  CONSTITUENTS  OF  URINE 

Chlorids. — 'The  inorganic  or  mineral  constituents  of  urine  consist 
principally  of  chlorids,  phosphates,  sulphates  and  carbonates  of  sodium, 
potassium,  ammonium,  calcium,  and  magnesium.     The  total  amount 
1  Mosenthal,  Arch.  Int.  Med.,  xvi,  1915,  733. 


1082  EXCRETION 

of  these  salts  varies  between  19  and  25  grm.  per  dsLj,  of  which  sodium 
chlorid  is  the  most  abundant,  because  it  is  excreted  in  amounts  of  10 
to  16  grm.  in  a  day.  Evidently,  the  chlorids  of  the  urine  are  derived 
almost  wholly  from  the  chlorids  of  the  food  and  hence,  their  amount 
must  vary  verj'  closely  with  the  character  of  the  material  ingested.  If 
the  latter  is  rendered  relatively  chlorin  free,  the  chlorids  may  dis- 
appear almost  completely  from  the  urine,  although  the  blood  retains 
its  normal  composition  in  this  regard.  Quite  similarly,  the  intake  of 
large  quantities  of  table  salt  raises  the  chlorin  content  of  the  urine. 
It  is  diminished  in  certain  diseases,  such  as  acute  pneumonia. 

Sulphates. — The  sulphates  of  urine  are  principally  those  of  potas- 
sium and  sodium,  but  since  the  salts  of  sulphuric  acid,  owing  to  their 
bitter  taste,  etc.,  do  not  form  an  important  constituent  of  our  food, 
the  sulphates  in  the  urine  are  derived  almost  exclusiveh'  from  the 
oxidation  of  the  sulphur  of  the  proteins.  The  nitrogen  of  these  sub- 
stances leave  the  body  chiefly  as  urea,  while  their  sulphur  constituents 
are  converted  into  sulphuric  acid  which  is  passed  into  the  urine  in  the 
form  of  sulphates.  Consequently,  the  output  of  sulphates  may  be 
employed  as  an  index  of  protein  metabolism,  in  the  same  way  as  urea. 
The  average  daily  output  of  sulphates  varies  between  1.5  and  3.0  grm. 

In  addition  to  the  sulphates  of  the  alkahne  metals,  urine  also  con- 
tains a  small  proportion  of  them  in  the  form  of  conjugated  or  ethereal 
sulphates  (10  per  cent.),  principally  as  phenyl  sulphate  and  indoxyl 
sulphate  of  potassium.  The  latter  originates  in  largest  part  in  the 
putrefactive  processes  within  the  intestine,  chiefly  from  indole,  and  as 
it  j-ields  indigo  when  treated  with  certain  reagents,  it  is  usually  called 
indican.  The  presence  of  this  substance  is  of  some  importance,  be- 
cause it  allows  us  to  estimate  the  intensity  of  intestinal  putrefaction 
and  the  power  of  our  body  to  convert  these  poisonous  derivatives  into 
the  innocuous  ethereal  sulphates.  A  small  proportion  of  the  sulphur 
contained  in  urine,  is  present  as  neutral  sulphur  representing  its  un- 
oxidized  form. 

Carbonates. — These  salts  are  present  only  in  alkaline  urine,  and 
are  represented  by  the  carbonates  and  bicarbonates  of  sodium,  calcium, 
magnesium,  and  ammonium.  They  arise  from  the  carbonates  of  the 
food,  and  must,  therefore,  be  most  evident  in  herbivora  and  vege- 
tarians. A  urine  of  this  kind  becomes  cloudy  on  standing,  owing  to 
the  precipitation  of  its  carbonates,  chiefly  calcium  carbonate,  and  also 
phosphates. 

Phosphates. — These  salts  are  derived  partly  from  the  phosphates 
of  the  food  and  partly  from  the  oxidation  of  the  organic  phosphorus- 
containing  bodies  of  the  tissues,  such  as  nuclein,  lecithin,  etc.  Their 
daily  excretion  varies  between  1.0  and  5.0  grm.,  calculated  as  P2O5, 
and  is  almost  wholly  dependent  upon  the  phosphate  content  of  the 
food.  Thus,  if  much  calcium  or  magnesium  is  present  in  the  latter, 
they  are  excreted  in  the  feces  as  calcium  and  magnesium  phosphate, 
sometimes  as  much  as  30  per  cent,  of  the  total  choosing  this  medium 


THE    COMPOSITION    OF   THE    URINE  1083 

for  Icavinp;  the  body.  The  nMiuiinder  exists  in  the  urine  as  rnono- 
and  disodiuni  hydrogen  phosphate,  the  amount  of  each  varying  with 
the  reaction  of  this  medium.  If  neutral  or  alkahne,  a  deposit  of 
earthy  phosphates  results  which  may  inmiediatcly  he  cleared  up  by  th(! 
addition  of  acid.  This  condition  generally  arises  after  a  copious  vege- 
table diet,  when  a  large  amount  of  disodiuni  hydrogen  phosphate  is 
produced.  Quite  similarly,  an  abundant  ingestion  of  protein  sub- 
stances, gives  rise  to  an  acid  urine,  owing  to  the  ff)rmntion  of  sulphuric 
and  other  acids.  In  the  latter  case,  there  is  a  greater  formation  of  phos- 
phoric acid  and  production  of  monosodium  hydrogen  phosphate. 

On  standing,  the  urine  assumes  an  alkaline  reaction,  owing  to  the 
conversion  of  the  urea  by  the  micro-organisms  into  ammonium  car- 
bonate. Under  these  circumstances,  a  creamy  white  precipitate  is 
formed  which  consists  of  triple  phosphate  or  ammonium-magnesium 
phosphate,  and  stellar  phosphate  or  calcium  phosphate.  It  should  be 
remembered,  however,  that  even  normal  human  urine  contains  a 
small  quantity  of  ammonia,  i.e.,  from  0.6  to  0.8  grm.  in  a  day. 
This  amount  may  serve  as  an  index  of  the  excess  of  acids  over  bases 
which  are  to  be  excreted.  While  it  is  possible  to  vary  this  amount  arti- 
ficially, for  example,  by  the  administration  of  mineral  acids,  any 
increase  during  the  normal  ingestion  of  food  invariably  signifies  that 
abnormal  acid  substances  are  formed  in  the  body.  This  is  the  case  in 
diabetes  mellitus,  a  disease  in  the  course  of  which  the  fatty  acids 
accumulate  in  consequence  of  their  diminished  oxidation.  This  accu- 
mulation must  necessarily  lead  to  a  rise  in  the  ammonia  content  of  the 
urine. 

THE  ORGANIC  CONSTITUENTS  OF  URINE 

Urea  or  Carbamide. — The  greatest  amount  of  the  organic  material 
in  urine  is  made  up  of  nitrogenous  bodies  which  are  derived  from  the 
proteins  of  the  food.  We  have  seen  that  the  substances  are  broken 
up  in  the  intestinal  canal  into  their  amino-acids  which  after  their 
absorption  are  either  converted  into  the  proteins  of  the  tissues  or  are 
diamidized.  In  the  latter  case,  the  principal  portion  of  the  carbon, 
oxygen,  and  hydrogen  is  oxidized  to  form  CO2  and  water,  whereas  the 
smaller  portion  is  combined  with  nitrogen  to  form  urea,  ammonia, 
uric  acid,  and  other  bodies.  This  same  fate  awaits  the  tissue-proteins 
which  are  constantly  broken  down  and  replaced  b}^  new  material.  It 
has  also  been  pointed  out  above  that  by  far  the  largest  amount  of  the 
nitrogen  of  the  food  is  excreted  in  the  urine,  and  that  only  a  small 
portion  of  it  enters  the  feces  or  is  lost  in  the  sweat.  Consequently, 
the  total  nitrogen  content  of  the  urine  gives  in  a  fair  way  the  total 
amount  of  nitrogen  ingested,  because  under  ordinary  conditions,  the 
body  is  in  nitrogen-equilibrium  and  its  N-ingo  equals  its  N-outgo. 
This  relationship,  however,  does  not  hold  true  when  the  bod}'  is  grow- 
ing and  needs  nitrogenous  material  for  the  construction  of  its  cells.  It 
may  also  be  disturbed  for  a  time  for  other  reasons.     Thus,  a  reduc- 


1084  EXCRETION 

tion  in  the  amount  of  the  proteins  ingested  finally  causes  a  diminution 
of  the  body-proteins,  which  in  turn  arc  drawn  upon  later  on  to  make 
good  the  loss  in  the  intake.  Quite  similarly,  any  increase  in  the  protein 
content  of  the  food  gives  rise  to  an  increase  in  the  nitrogen  of  the  urine. 
The  nitrogen  metabolism  of  the  body,  however,  cannot  be  estimated 
precisely  unless  a  comparison  is  made  between  the  total  nitrogen  of 
the  urine  and  the  amount  of  nitrogen  ingested,  because  only  when 
both  factors  are  known  is  it  possible  to  determine  the  character  of 
the  intermediary  processes. 

The  most  important  nitrogenous  constituent  of  urine  is  urea. 
Formerly  thought  to  be  produced  in  the  kidneys,  it  is  now  a  well 
established  fact  that  it  arises  elsewhere  in  the  body  and  is  brought  to 
these  organs  in  the  form  of  a  rather  complete  precursor.  The  renal 
cells,  therefore,  merely  remove  this  product  from  the  blood  by  virtue 
of  a  peculiar  selective  power.  We  know  this  to  be  true,  because  the 
formation  of  urea  and  other  waste  products  of  this  type  continues 
even  after  the  kidneys  have  been  extirpated  or  have  been  rendered 
functionally  useless  by  disease.  This  substance  then  accumulates  in 
the  blood  and  gives  rise  to  the  condition  of  uremia.  It  should  be 
noted,  however,  that  the  poison  acting  at  this  time,  is  not  the  urea  nor 
any  other  normal  constituent  of  urine,  but  some  intermediary  product 
of  protein  catabolism.  The  question  pertaining  to  the  place  of  origin 
of  this  substance  seems  to  have  been  decided  in  favor  of  the  liver, 
because : 

(a)  The  removal  of  this  organ  in  mammals  proves  fatal  owing  to  the  accumula- 
tion of  certain  catabolic  substances.  This  is  indicated  by  the  gradual  diminution 
of  the  urea  content  of  the  urine.  A  similar  effect  may  be  produced  by  the  establish- 
ment of  an  Eck  fistula,  the  urea  of  the  urine  then  being  lessened  and  the  ammonia 
increased. 

(b)  The  extirpation  of  the  liver  in  the  frog  and  allied  animals  brings  aljout  a 
substitution  of  the  urea  by  ammonia. 

(c)  Such  diseases  as  cirrhosis  and  yellow  atrophy  of  the  liver  are  characterized 
by  a  similar  change.  In  the  latter  case,  the  amino-aoids,  such  as  leucine  and 
tyrosine,  appear  in  the  urine,  because  they  escape  further  reduction  in  the  liver 
and  pass  directly  into  the  urine. 

(d)  If  amino-acids,  such  as  glycine,  leucine,  arginine,  and  others  are  adminis- 
tered by  the  mouth  or  are  injected  into  the  blood-stream,  the  urea  excretion  is 
increased. 

This  view,  that  urea  is  the  result  of  a  conversion  of  the  amino-acids 
by  the  cells  of  the  liver,  is  also  strengthened  by  the  fact  that  some  of 
these  bodies  may  be  made  to  undergo  this  change  in  the  test  tube. 
In  the  case  of  arginine,  Kossel  and  Dakin^  have  found  that  it  consists 
of  a  urea  radicle  and  a  substance  known  as  ornithine.  On  hydrolysis 
it  splits  into  urea  and  ornithine.  This  same  reaction  is  supposed  to 
occur  in  the  liver  under  the  influence  of  arginase,  the  arginine  then 
being  split  up  into  simpler  compounds  which  are  again  combined 
1  Zeitschr.  fur  Physiol.  Chemie,  xlii,  1904,  181. 


THE    COMPOSITION    OF    THE    URINE  1085 

differently  into  urea.  Schroder'  has  shown  tluit  one  of  these  simple 
compounds,  although  not  the  principal  one,  is  ammonium  carbonate. 
Thus,  it  may  be  concluded  that  urea  is  a  synthetic  product  of  the  liver 
cells. 

In  accordance  with  our  previous  discussion,  urea  may  be  regarded 
as  partly  exogenous,  and  partly  endogenous,  because  it  is  derived,  on  the 
one  hand,  from  nitrogenous  bodies  which  have  been  absorbed  but  have 
not  become  intimate  constituents  of  the  tissue  cells,  and,  on  the  other, 
from  bodies  which  have  been  discharged  by  the  cells  after  they  have 
previously  formed  a  part  of  them.  In  other  words,  urea  finds  its 
origin  in  the  circulating  proteins,  as  well  as  in  the  tissue  proteins.  It 
may  then  be  reasoned  that  a  person  in  nitrogen-equilibrium  discharges 
only  a  small  and  rather  constant  amount  of  tissue  proteins  and  that, 
therefore,  the  endogenous  urea  must  possess  a  small  and  constant  value. 
Contrariwise,  it  may  be  assumed  that  the  amount  of  the  exogenous 
urea  is  much  larger  and  variable,  because  it  is  taken  from  the  variable 
and  excess  quantities  of  proteins  ingested.  It  is  true,  however,  that 
the  endogenous  variety  may  also  undergo  marked  alterations,  for 
example,  in  fevers  and  other  pathological  conditions  causing  a  rapid 
destruction  of  the  tissue  proteins. 

Although  subject  to  variations  for  reasons  just  stated,  the  amount 
of  urea  excreted  in  the  course  of  a  day  is  usually  given  as  33  to  35 
grm.,  provided  about  100  to  120  grnt.  of  protein  are  ingest ed.- 
Its  amount  becomes  greatest  three  hours  after  a  mixed  meal  and  may 
constitute  as  much  as  90  per  cent,  of  the  total  nitrogen  if  large  quanti- 
ties of  protein  are  ingested.  Upon  a  low  protein  diet,  such  as  has  been 
advocated  by  Chittenden,  the  urine  shows  a  nitrogen-content  consid- 
erably below  that  ordinarily'  regarded  as  normal.  The  proportion 
of  urea  may  then  be  diminished  to  60  per  cent.,  because  its  chief  source, 
the  exogenous  nitrogen,  has  been  eliminated  in  part.  Muscular  exer- 
cise does  not  affect  the  urea  output,  showing  that  the  energy  is  derived 
in  this  case  from  the  combustion  of  non-nitrogenous  substances, 
chiefly  the  carbohydrates.  Some  authors  also  state  that  a  direct 
relationship  exists  between  the  rate  of  urine  secretion  and  the  amount 
of  urea  in  the  blood  and  urine,  and  claim  to  be  able  to  evaluate  the 
functional  power  of  the  kidnej'  by  a  comparison  of  these  factors.^ 

Urea  possesses  the  formula  CO(XH2)2  and  is  isomeric  with  ammo- 
nium cyanate  (NH4CNO).  This  implies  that  it  has  the  same  empirical 
but  not  the  same  structural  formula.  This  substance  was  employed 
by  Wohler  in  1828  in  the  sj-nthetic  preparation  of  urea.  Crystals  of 
this  substance  may  be  obtained  by  warming  potassium  cyanate  to- 
gether with  ammonium  chlorid.  In  this  form,  urea  is  readilj-  soluble 
in  water  and  alcohol  and  possesses  a  salty  taste  and  a  neutral  reaction 
to  litmus      On  treatment  with  nitric  acid,  the  nitrate  of  urea  is  formed 

1  Archiv  fiir  exp.  Path,  und  Pharm.,  xv,  1882,  364. 

-  Addison  and  Watanabe,  Jour.  Biol.  Chem.,  xxvii,  1917,  381. 

^  Ambard  and  Weil,  Physiol,  norm,  et  path,  des  reins,  Paris,  1914. 


1086  EXCRETION 

(CON2H4.HNO3),  and  on  treatment  with  oxalic  acid  its  oxalate  (CON2 
H4.H2C2O4+H2O).  Urea  melts  at  130°  C,  undergoing  finally  a  decom- 
position which  yields  ammonia,  biuret  and  cyanic  acid,  the  latter 
being  polymerized  to  cyanuric  acid.  On  hydrolysis  by  means  of 
heating  with  strong  acids  or  alkalies,  it  yields  carbon  dioxid  and 
ammonia. 

Ammonia. — The  urine  of  man  and  the  carnivora  contains  a  small 
quantity  of  ammonium  salts  which  serve  as  a  means  of  transfer  for 
the  acid  radicles  which  have  been  ingested  or  have  been  formed  in 
the  body.  The  chief  source  of  these  salts  is  the  ammonia  of  the  blood, 
derived  from  the  nitrogenous  portion  of  the  diamidized  amino-acids. 
This  ammonia  is  carried  to  the  liver  where  urea  is  synthetized,  but 
some  of  it  escapes  and  reaches  the  kidneys  where  it  slips  through  into 
the  urine.  Some  of  it  is  also  derived  from  the  ammonium  salts  in- 
gested from  the  ammonia  produced  in  the  course  of  the  intestinal 
putrefaction  of  the  proteins.  In  the  body,  it  exists  as  ammonium 
carbonate  which  is  the  precursor  of  urea.  It  is  for  this  reason  that  so 
little  of  it  circulates,  but  when  mineral  acids  are  administered,  or  when 
excessive  quantities  of  acids  are  produced,  as  in  diabetes  mellitus,  the 
body  makes  use  of  the  ammonia  as  a  base  and  an  extra  amount  of  it 
appears  in  the  urine.  An  excess  of  alkali,  on  the  other  hand,  causes 
it  to  be  transferred  into  urea  and  to  disappear  as  such  from  the  urine. 
This  accounts  for  the  fact  that  it  is  not  present  in  the  urine  of  vege- 
tarians nor  in  that  of  the  herbivora.  Ordinarily,  the  daily  output  of 
ammonia-nitrogen  varies  between  0.3  and  1.2  grm.,  the  average  being 
0.7  grm.,  or  3.5  per  cent,  of  the  total  amount  of  nitrogen. 

Acidosis. — It  has  been  known  for  some  years  that  the  urine  of 
diabetics  is  loaded  with  acetone,  diacetic  acid  and  /S-oxybutyric  acid. 
It  was  supposed  at  first  that  these  bodies  are  derived  from  glucose, 
because  they  are  present  in  glycosuria,  but  it  is  now  known  that  they 
are  the  result  of  a  disordered  process  of  breaking  down  the  fats. 
Ordinarily,  this  foodstuff  is  converted  into  carbon  dioxid  and  water, 
but  in  certain  abnormal  conditions  there  is  produced  /S-oxybutyric 
acid,  then  diacetic  acid  and  lastly,  acetone.  Since  a  small  amount  of 
acetone  is  normally  present  in  urine  and  especially  after  the  ingestion 
of  butter  consisting  of  the  lower  fatty  acids,  and  since  none  of  these 
substances  is  poisonous,  except  in  enormous  doses,  it  may  be  asked 
why  they  cause  such  serious  disturbances  when  formed  in  the  course  of 
metabolism.  Briefly,  the  answer  is  this:  Fats  are  converted  into  these 
abnormal  acids  instead  of  into  carbon  dioxid  and  water  whenever 
the  tissues  are  unable  to  obtain  sugar  from  the  blood.  The  blood  is 
normally  alkaline  and  the  functions  of  the  tissues  are  adapted  to  this 
particualr  reaction.  In  consequence  of  the  production  of  diacetic  and 
especially  of  |8-oxybutyric  acid,  its  alkalinity  is  greatly  reduced.  The 
functional  disturbances  then  ensuing  constitute  the  condition  of 
acidosis.  It  would  seem,  therefore,  that  an  artificial  supply  of  alkahes 
should  place  the  body  in  a  position  to  withstand  the  presence  of  these 


THi;    ((IMPOSITION    OF    THE    URINE  1087 

acids. ^  This  is  true  to  a  huge  extent,  because  even  the  body  attempts 
to  remedy  this  defect  by  caUing  to  its  defense  first  its  reserves  of 
Rodiuni  and  potassium  and  histly,  and  most  effectively,  large  quantities 
of  ammonia.  We  have  seen  that  the  proteins  turn  their  effete  nitrogen 
into  annnonium  carbonate  and  carbamate  which  are  tiien  converted 
into  urea  in  the  liver.  When  the  body  employs  this  ammonia  as  a 
defense,  it  combines  it  with  the  diacetic  and  /3-oxybutyric  acids  and 
does  not  convert  it  into  urea.  Consequently,  the  ammonia  escapes  in 
this  case  into  the  urine  as  ammonium  diacetate  and  ammonium 
/3-oxybutyrate.  Finally,  when  the  body  has  reached  its  limit  in  this 
regard,  the  normal  alkalinity  of  the  blood  can  no  longer  be  maintained 
and  dyspnea,  collapse  and  coma  result. 

Creatin  and  Creatinin  (CHrXriO). — On  a  diet  free  from  meat, 
creatin  is  excreted  in  amounts  varying  between  7  and  11  mgr.  per 
kilogram  of  body  weight.  Folin^  regards  it  as  a  criterion  of  the  inten- 
sity of  the  endogenous  nitrogenous  metabolism  and  believes  that  it  is 
formed  in  the  liver  and  not  in  the  muscles  which  usually  contain  it 
in  abundant  amounts.  Any  gross  variation  from  the  amount  just 
given  signifies  an  accumulation  of  this  substance  in  the  blood.  Mel- 
lanby  claims  that  creatinin  is  derived  from  certain  derivatives  of 
protein  catabolism  in  the  liver  and  is  then  convej^ed  from  this  organ 
to  the  muscles,  where  it  is  converted  into  its  anhydride,  creatin.  As 
soon  as  this  tissue  becomes  saturated  with  this  substance,  creatinin 
is  excreted  in  the  urine,  and  hence,  a  renal  deficiency  would  invariably 
be  followed  by  an  accumulation  of  the  latter  in  the  blood. 

Uric  Acid  (C5H4X4O3). — The  quantity  of  uric  acid  normally  present 
in  the  urine  of  man  is  small.  It  varies  between  0.3  and  1.2  grm.  per 
day  or  between  0.02  to  0.10  per  cent.  This  amount  may  be  derived 
from  the  ordinary  purin  metabolism  of  the  body  (endogenous)  or  from 
the  food  ingested  (exogenous).  For  this  reason,  it  may  readily  be 
increased  by  the  ingestion  of  food  rich  in  nucleins,  or  substances 
containing  the  purin  bases  in  a  free  state.  Since  the  human  body 
does  not  possess  the  power  of  destroying  any  of  the  uric  acid,  it  must 
be  excreted  as  such  in  the  urine.  This  being  the  case,  one  of  the 
earhest  symptoms  of  renal  insufficiency  is  the  increase  of  uric  acid  in 
the  bloo(i.  The  reason  for  this  is  not  quite  clear,  unless  it  is  taken 
into  account  that  its  salts  are  the  least  soluble  of  any  excreted  in  the 
urine.  This  also  explains  the  fact  that  urine  when  cooled,  yields  a 
pink  deposit  of  urates.  Uric  acid  is  present  in  large  amounts  in  the 
urine  of  birds  and  snakes,  forming  here  acid  ammonium  urate. 

The  purin  bases  are  largely  transformed  into  uric  acid  and  only 
their  residue  appears  in  the  urine.  Only  traces  of  hippuric  acid  are 
present  under  normal  conditions  (0.7  grm.  per  day),  but  the  ingestion 
of  fruits  and  vegetables  may  raise  it  to  2  grm.  per  day.     Amino-acids 

1  Von  Noorden,  "Diabetes  Mellitus,"  Wright  and  Sons,  Bristol,  1906. 
*  Am.  Jour,  of  Physiol.,  xiii,  1905,  66  and  Jaffc^.  Zeitschr.  fur  physiol.  Chemie., 
xlviii,  1906,  430. 


1088  EXCRETION 

may  also  be  present  in  amounts  equalling  1.5  per  cent,  of  the  total 
nitrogen.  1  Aromatic  oxyacids,  such  as  phenol,  indoxyl  and  skatoxyl, 
are  normally  present  in  varying  amounts,  and  serve  as  an  indication 
of  the  putrefactive  decomposition  of  the  proteins  in  the  large  intestine. 
Ordinarily,  the  body  protects  itself  by  oxidizing  them  and  combining 
them  to  sulphuric  acid  to  form  the  ethereal  sulphates. 

1  Van  Slyke  and  G.  IM.  Meyer,  Jour.  Biol.  Chem.,  xvi,  1913,  197. 


SECTION  XXIX 
ANIMAL  HEAT 


CHAPTER  XCTI 
THE  PRODUCTION  AND  DISSIPATION  OF  HEAT 

Thermometry  and  Calorimetry. — Inasmuch  as  all  cheuiical  proc- 
esses require  an  optinmni  degree  of  temperature  for  their  completion, 
it  may  be  concludetl  that  the  assimilation  and  dissimilation  of  the 
different  foodstuffs  cannot  be  effected  in  the  absence  of  a  definite 
measure  of  heat.  This  heat  may  be  derived  from  two  sources,  namely, 
as  radiating  or  bound  energy  from  without,  or  as  energy  liberated  in  the 
course  of  the  different  chemical  changes  to  which  the  tissues  and  organs 
of  the  body  are  subject.  Under  ordinary  circumstances,  the  latter 
form  of  heat  is  of  by  far  the  greatest  functional  importance  to  us,  but 
its  detection  and  actual  measurement  presents  many  rather  unexpected 
difficulties,  so  that  very  sensitive  instruments  must  be  employed  in 
order  to  prove  its  liberation.  In  the  case  of  such  structures  as  the 
muscles  and  glands,  we  make  use  of  the  so-called  thermo-electric  ele- 
ments which  consist  of  two  dissimilar  metals,  such  as  German  silver 
and  iron,  soldered  together.  One  of  these  is  placed  in  some  indifferent' 
tissue  or  in  the  blood-stream,  while  the  other  is  inserted  in  the  organ, 
the  temperature  of  which  is  to  be  determined.  If  the  binding  posts 
of  these  two  pairs  of  elements  are  then  connected  with  a  galvanometer, 
it  will  be  found  that  the  least  production  of  heat  at  the  point  of  solder- 
ing gives  rise  to  a  difference  in  potential  which  will  be  accurately  in- 
dicated by  the  deflectijon  of  the  galvanometric  needle. 

It  is  evident,  however,  that  this  method  cannot  be  employed  to 
determine  the  total  heat-production  of  an  animal  nor  its  body-tempera- 
ture, because  this  method  must  necessarily  remain  restricted  to  single 
and  separate  organs.  Should  we  desire  to  determine  the  temperature 
prevailing  within  the  body  of  an  animal  we  must,  of  course,  make  use  of 
a  thermometer  which  is  inserted  in  any  one  of  its  cavities  or  recesses 
and  is  allowed  to  remain  there  until  the  mercurial  indicator  has  as- 
sumed a  stationary  position.^  It  must  be  evident,  however,  that 
thermometry  merely  serves  as  a  means  of  determining  the  tempera- 
ture existing  at  any  particular  moment  and  cannot  yield  data  regarding 
the  total  amount  of  heat  produced  by  the  animal.     Should  we  wish  to 

*  The  thermometer  was  devised  by  Galilei  in  1603.     The  first  thermometric 
determinations  upon  man  were  made  by  Sanctorius  in  1626. 
69  1089 


1090 


ANIMAL    HEAT 


ascertain  the  latter  factor,  it  becomes  necessarj"  to  employ  an  instru- 
ment which  is  known  as  the  calorimeter,^  and  presents  itself  in  the  form 
of  two  modifications,  designated  as  the  water-calorimeter  and  air- 
calorimeter.  In  either  case,  this  apparatus  consists  of  a  central 
compartment  in  which  the  animal  is  kept,  and  a  narrow  outer  com- 
partment which  is  filled  either  with  water  or  with  air.  Externally  its 
walls  are  covered  with  a  heavy  layer  of  some  non-conductile  material 
to  prevent  all  losses  of  heat.     The  heat  liberated  by  the  animal  is  then 


C71  WFT 


lEXT 


Fig.  527. — Water  Calorimeter.     (Reichert.) 
A,    Inner  compartment  for  animal;  SH,  space  filled  with  non-conductile  material; 
EXT  and  EXT,  tubes  for  the  respiratory  air;  CT,  thermometer  in  jacket  filled  with 
water;  S,  stirrer  to  equalize  the  temperature  of  the  water. 

transmitted  to  the  water,  the  temperature  of  which  is  read  off  by 
means  of  a  stationary-  thermometer.^  In  the  case  of  the  air  calorime- 
ter, the  heat  evolved  by  the  animal  gives  rise  to  an  expansion  of  the 
air  contained  in  the  outer  compartment,  which  is  then  transferred  by 
calculation  into  degrees  of  heat.  Consequently,  since  the  total  amount 
of  the  animal's  heat  is  derived  under  this  condition  from  the  chemical 
energy  of  its  food,  the  former  must  constitute  a  direct  index  of  the 
oxidative  processes. 

The  unit  generallj-  employed  in  measuring  the  amount  of  heat 

^  The  first  calorimeter  experiments  upon  animals  were  made  by  Lavisier  and 
Laplace  in  1780  (Mem;  de  I'Acad.  d.  Sciences). 

-  Equally  large  masses  of  different  bodies  require  different  amounts  of  heat, 
that  of  water  being  nine  times  greater  than  that  of  iron. 


THE    PRODUCTION    AND    DISSIPATION    OF    HEAT 


1091 


evolved  is  the  calorie,  i.e.,  the  (luuntity  of  heat  whicli  is  necessary  to 
raise  1  kilogram  of  water  1°  C.  (from  15°  to  16°  C).  We  also  speak  at 
times  of  the  small  calorie  which  refers  to  the  amount  of  heat  which  is 
required  to  raise  1  gram  of  water  1°  C.  Supposing,  therefore,  that  the 
quantity  of  water  in  the  calorimeter  weighs  10  kilos  and  that  the 
temperature  rises  1°  C.  every  half-hour,  then  the  amount  of  heat  liber- 
ated by  the  animal  during  this  time  amounts  to  10  calories  or  to  480 
calories  in  the  course  of  a  day.  This  calculation,  however,  can  be 
correct  only  if  the  body-temperature  of  the  animal  has  remained  the 
same  during  this  period,  and  if  the  metal  of  the  calorimeter  has  not 
absorbed  an  undue  amount  of  this  heat.  The  latter  factor  cannot 
possibly  interfere  with  this  determination  if  the  instrument  is   well 


SCALE       i     METER 


Fig.  528. — Schematic  Outline  of  the   Respiration'  Calorimeter. 
A,   Dead  air  space  between  copper  and  zinc  walls;  B,  dead  air  space  between  zinc 
wall  and  wooden  wall;  C,  dead  air  space  between  inner  and  outer  wooden  walls.     E, 
tube  for  food;  S  and   H,  inlet  and  outlet  for  water;  V,  air  circulation.      {Atwater  and 
Benedict.) 

protected  against  heat-loss,  and  if  the  experiment  is  continued  for  a 
relatively  long  period  of  time. 

More  recently,  Atwater  has  made  use  of  calorimeters  large  enough 
to  accommodate  human  beings,  so  that  the  heat  produced  by  them  may 
be  brought  into  relation  with  their  respiratory  interchange.  The 
air  within  this  chamber  is  kept  at  a  constant  temperature  by  a  stream 
of  water  passed  through  it  in  a  series  of  tubes.  If  the  temperature 
of  this  water,  as  well  as  the  volume  of  the  through  flow  which  is  required 
to  accomplish  this  end,  is  then  ascertained,  it  is  possible  to  obtain 
from  these  values  the  amount  of  heat  Hberated  by  the  person.  Besides, 
air  is  drawn  out  of  this  chamber  by  an  engine,  its  volume  being  reg- 
istered by  a  gas-meter.  From  time  to  time  samples  of  this  air  are 
withdrawn  for  analysis  which  includes  the  determination  of  its  carbon 


1092 


ANIMAL   HEAT 


dioxid  content  by  means  of  baryta  water  and  of  its  aqueous  vapor  by 
means  of  drying-tubes  containing  sulphuric  acid.  These  values  are 
then  compared  with  the  data  derived  from  analyses  of  the  air  entering 
the  calorimeter.  These  principles  which  have  first  been  made  use 
of  by  Pettenkofer,  are  also  embodied  in  the  micro-calorimeter  of  Hill.^ 
This  apparatus  which  is  especiall}-  adapted  for  the  detection  of  very 
small  amounts  of  heat,  consists  of  two  thermos  bottles  in  which  the 
loss  of  heat  is  prevented  by  exhausting  the  air  from  the  space  between 
their  outer  walls.  Each  bottle  is  equipped  with  thermo-electric 
elements  which  are  connected  in  turn  with  a  galvanometer.  Both 
are  packed  in  sawdust.  The  organ  to  be  experimented  upon  is  then 
placed  in  one  of  these  bottles,  while  the  other  is  filled  with  water  as  a 


^ 


0  introduced. 


o  deficient 


P>ES  PI  RATION  CHAMBER 
0  u^ed 


I        COz 
absorbed  b 
(No.  OH 


1 I    TiTo 

absorbed  by 


l_(^^rL±!!i 


COs    O  deficient 


ROTARY 


Fig.  529.- 


-DiAGR-VM  Showing  CracuL-^Tiox  of  Air  through  the  Respiratiox  Calori- 
meter.     {Atwater   and   Benedict.) 


control.     This  apparatus  is  sensitized  to  detect  one  small  calorie  of 
heat  per  gram  of  tissue  during  a  period  of  10  hours. 

Sources  of  Heat.  Thermogenesis. — While  there  is  always  a  small 
and  variable  amount  of  heat  imparted  to  living  beings  from  without, 
their  principal  source  of  heat  lies  in  the  chemical  processes  evoked 
within  their  different  tissues  and  organs.  Every  contraction  of  mus- 
cle, every  act  of  secretion,  and  even  every  nervous  reaction  gives  rise 
to  a  small  amount  of  heat,  which  together  then  form  the  total  quantity 
of  heat  evolved  by  the  animal.  These  cellular  oxidations  consist 
essentially  of  a  union  of  oxygen  with  carbon  and  hydrogen  to  form 
carbon  dioxid  and  water.  In  last  analysis,  therefore,  the  body-heat  is 
derived  from  the  food  taken  into  the  body.  Other  processes  of  dis- 
integration, such  as  are  effected  by  hydrolysis,  also  produce  a  certain 

1  Jour,  of  Physiol.,  xlv,  1918,  261,  and  ibid.,  xlvi,  1913,  81 ;  also :  Williams,  Jour. 
Biol.  Chem.,  xii,  1912,  349. 


THE    PRODUCTION    AND    DLSSIPATION    OF    HEAT  1093 

amount  of  lu'iit  which,  liowcvcr,  is  never  considorahlo.  Inasmuch  as 
tho  hiw  of  the  conservation  of  energy  is  directly  appHcable  to  th(^  ani- 
mal l>ocly,  these  processes  must  serve  to  convert  latent  or  potential 
energy  into  its  kinetic  form.  Consequently,  the  ultimate  source  of 
heat  is  the  potential  energy  of  the  food,  and  it  matters  little  whether 
this  material  be  slowly  oxidized  in  the  body  or  be  burned  up  in  a 
calorimeter.  In  both  cases,  compU^x  substances  are  reduced  into 
relativelj^  simple  bodies  under  an  evolution  of  energy  which  manifests 
itself  as  mechanical  energy,  heat,  and  electricity.  This  combustion, 
however,  remains  incomplete  at  times,  as  is  shown,  for  example,  by 
the  proteins  which  always  leave  a  residue  of  urea,  uric  acid  and  other 
substances.  Consequently,  any  calculation  of  the  total  heat-energy 
of  a  given  foodstuff  must  take  into  account  the  energy  of  this  possible 
residue.  Carbohydrates  and  fats,  on  the  other  hand,  are  oxidized 
completely. 

Body-temperature. — Since  all  the  tissues  of  our  body  take  part  in 
these  processes  of  oxidation,  every  cell  in  our  body  maj^  be  said  to  be 
a  producer  of  heat.  Admittedly,  however,  tissues  differ  very  markedly 
in  their  activities,  and  hence,  also  in  the  quantity  of  heat  evolved  by 
them.  The  most  important  heat-generating  organ  is  the  skeletal 
musculature,  because  it  is  hardly  ever  at  rest,  and  because  more  than 
one-haK  of  the  total  weight  of  the  soft  parts  of  our  body  is  made  up  of 
this  type  of  tissue.  Next  in  order  are  the  glands.  In  either  case, 
an  active  organ  is  always  warmer  than  a  resting  organ  or  the  body- 
fluids,  and  hence  the  heat  must  be  transmitted  from  the  former  to  the 
latter.  In  the  nature  of  things,  the  chief  and  final  heat  absorbing 
agent  is  the  blood  w^hich  by  virtue  of  its  velocity  quickly  removes  the 
superfluous  heat  from  the  seats  of  the  oxidations,  thereby  tending  to 
keep  the  temperature  approximately  uniform  throughout.  Later  on, 
when  the  blood  enters  the  more  exposed  portions  of  our  body,  it  loses 
a  part  of  its  heat  either  by  radiation  or  in  the  form  of  bound  heat. 

It  is  evident,  therefore,  that  the  blood  and  lymph  form  a  medium 
into  which  the  different  tissues  pour  their  heat  and  which  by  virtue  of 
its  motion  tends  to  equalize  the  temperature  of  the  different  parts  of 
the  body,  and  also  to  bring  the  latter  into  proper  heat-relation  with 
the  surrounding  air.  In  accordance  with  their  resistance  to  outside 
influences,  animals  may  be  divided  into  two  classes,  namely,  into  those 
which  are  and  those  which  are  not  protected  against  a  loss  of  heat. 
This  functional  difference  brings  it  about  that  the  former  are  capable 
of  retaining  a  relatively  constant  temperature  in  spite  of  the  fact  that 
the  outside  temperature  may  vary  considerably,  while  the  latter  are 
not  and  must,  therefore,  be  subject  to  the  fluctuations  of  the  tempera- 
ture of  the  medium  in  which  thej'  live.  The  first  are  designated  as 
constant-temperatured,  homoiothermal  or  warm-blooded  animals,  and 
the  se'dond  as  inconstant-temperatured,  poikilothermal,  or  cold-blooded 
animals.  But  sin'oe  the  poikilothermal  animals  may  be  made  to  attain 
a  body-temperature  equalling  and  even  surpassing  that  of  the  homoio- 


1094  ANIMAL   HEAT 

th(!rmal  animals,  the  terms  of  cold-ljloodod  and  warm-}jlf)od(!d  arc  not 
woll  chosen.  This  classification,  therefore,  rests  upon  their  power  of 
retaining  a  relatively  constant  body-temperature. 

It  should  he  notcid  (ispc^cially  that  the;  t(!mperature  of  the  poikilo- 
thermal  animals  is  invariably  som(!what  higher  than  that  of  the 
medium  in  which  they  live.  This  discrepancy  cannot  surprise  us, 
because  even  an  apparently  perfectly  inactive  animal  cannot  suppress 
its  metabolism  entirely,  and  hence,  since  it  must  generate  at  least  a 
slight  amount  of  heat,  its  temp(!iatur(!  must  remain  at  least  a  degree 
or  two  above  that  of  the  surrounding  medium.  In  other  words, 
even  cold-blooded  animals  store  their  heat  in  a  certain  measure,  but 
this  storage  is  nev(!r  considerable,  because  they  are  relatively  unpro- 
tected against  heat-loss  and  secondly,  because;  their  metabolism  p(!r 
unit  of  weight  is  much  lower  than  thatof  th(!Wurm-blood(!d  animals.  It 
should  also  be  noted  that  the  temperature  of  the  warm-blooded  animals 
is  not  absolutely  uniform,  because  those  leading  a  more  active  life, 
possess  a  higher  body-t(!mp(!rature  than  those  which  do  not.  This 
becomes  apparent  immediatcsly  if  the  r(!ctal  temperature  of  the  birds 
(41°  to  44°  C.)  is  compared  with  that  of  the  mouse  (41°  C),  rabbit 
(39°  C),  dog  (38°  to  39°  C),  man  (37°  ().),  and  horse  (36°  C.  to  37°  C.).' 
With  the  exception  of  a  few  hibernating  animals,  which  are  homoiother- 
mic  in  summer  and  poikiloth(;rrnic  in  wintf^r,  the  temperature  of  the 
warm-blooded  animals  must  remain  rather  c<jnstant,  (;th(!rwis(;  c(!rtain 
conditions  may  arise  which  will  make  hfe  impossible. ^  The  vitality  of 
cold-blooded  animals,  on  the  other  hand,  is  not  seriously  impaired  by 
such  variations,  as  is  evinced  by  the  fact  that  the  temperature  of 
the  frog  may  be  r(!du(;(!d  from  25°  C.  to  5°  C.  without  producing  other 
symptoms  than  a  uicrc.  sluggishness  of  mov(!ment. 

The  Temperature  of  Different  Regions  of  the  Body. — It  has  been 
stated  above  that  tlie  different  tissues  of  our  l>ody  eliminate  heat  in 
amounts  corresponding  almost  precisely  with  the  intensity  of  their 
mcitabolism.  Th(!  musclcis  come  first,  then  the  glands,  and  lastly  the 
nervous  and  connective  tissues.  Furthermore,  while  the  heat  pro- 
duced by  them  is  directly  transmitted  from  part  to  part,  the  chief  and 
final  absorbing  m(;dium  is  the;  blood,  but  since  the  latter  cannot  equalize 
conditions  instantaneously,  some  internal  parts  must  always  be 
waruKir  than  oth(!rs.  This  is  true,  in  particular,  of  the  hver,  b(H;ause 
its  blood-vessels  are  well  protected  against  heat  loss,  and  because 
its  metabolism  is  never  at  a  standstill.  But,  the  blood  also  trav- 
erses certain  regions  which  li(!  in  imm(;diate  contact  with  the  medium 
and  which,  thcsrefon;,  are  more  dir(!ctly  exposed  to  the  influ(!nc(!  of  the 
latter.  Thus,  it  has  been  observed  that  the  temperature  of  the  skin 
in  the  vicinity  of  a  blood-vessel  is  higher  than  that  at  some  distance 
from  it,  and  that  the  temperature  of  the  blood  of  the  carotid  artery  is 

^  FroUiingham  and  Minot,  Am.  Jour,  of  Physiol.,  xxx,  1912,  4.30. 
'  Simpson,  Proc.  R.  Soc.  (Edinb.j  1912,  and  Proc.  Soc.  Exp.  Biol,  and  Med., 
1913. 


THE    PRODUCTION    AND    DISSIPATION    OF    HEAT  1005 

liif^lior  than  thtit  of  Iho  cxtonuil  juj2;ular  voin.  VcM-y  similar  (litYoivnces 
arc  tlisplayed  by  the  blood  of  thr  portal  vein  bofori'  aiul  after  nioals, 
as  well  as  by  the  blood  of  the  vein  draininji  a  nuiscle  when  the  latter 
is  either  allowed  to  rest  or  is  made  to  eontraet.  Even  the  mere 
raisin};  of  the  arm  above  the  lu^ad  siifliees  to  lower  the  temperature 
of  the  hand  0.2°  V. 

The  avera}j;e  temperature  of  the  blood  traversing  internal  channels, 
is  39°  to  40°  C\.  while  that  of  the  exposed  parts  may  be  only  28°  to 
35°  C.  Kunkel'  gives  the  following  values:  Foreheail  ;U.1°  i\,  cheeks 
34.4°  C,  tip  of  ear  28.8°  C,  sternum  34.4°  C,  and  thigh  34.2°  C.  In 
man,  the  body-temperature  is  measured  as  a  rule  by  placing  the  ther- 
mometer below  the  tongue,  care  being  taken  to  keep  the  lips  closed  to 
prevent  its  cooling  by  the  res]Mratory  currents  of  air.  In  atlults,  it 
may  also  be  measuretl  in  the  axilla,  and  in  childrei\  usually  in  tiic  rec- 
tum. While  the  time  during  which  the  thermometer  shouUl  be  left 
in  situ,  varies  with  its  sensitiveness,  2  to  3  minutes  usually  suffice 
for  its  indicator  to  reach  its  highest  l(>vel.  The  average  axillary  tem- 
perature is  30.9°  C,  the  oral  tcmjierature  37.1°  C,  and  the  rectal 
temperature  37.3°  ('. 

Factors  Varying  the  Body-temperature. — Wiiile  it  is  our  custom 
to  adhere  strictly  to  these  average  valuers,  it  should  be  renuMnbered 
that  certain  minor  tluct nations  are  not  at  all  unconunon.  In  other 
words,  even  the  liomoiotluMiual  animals  frequently  show  variations  in 
their  temperatuii'  which  are  brought  about  by  such  factors  as  age,  sex, 
time  of  day,  meals,  exercise,  season,  climate  and  clothing.  While 
these  deviations  rarely  amount  to  more  than  a  ilegree  or  two  and  are 
temporary  in  their  nature,  certain  conditions  may  also  arise  at  times 
which  produce  a  much  more  intense  and  lasting  difference.  Quite 
aside  from  the  ordinary  febrile  reactions,  the  outside  temperature  may 
be  raised  in  such  a  measure,  that,  owing  to  a  diniinished  loss  of  heat, 
the  body-temperature  quickly  mounts  to  40°C\and  over.  This  change 
is  usually  associated  with  the  symptoms  characterizing  fever  and  heat- 
stroke, i.e.,  with  an  increase  in  the  frequency  of  the  heart  and  respira- 
tion (heat-poly pnea),  fatigue,  headache  and  loss  of  consciousness. 
Wiien  the  rectal  temperature  rises  to  44°  C,  death  usually  results 
within  a  very  short  time. 

Hot  moist  air  is  far  more  oppressive  and  dangerous  than  hot  dry 
air,  owing  to  the  inability  of  the  bodj^  to  rid  itself  of  the  superfluous 
heat  by  sweating.  In  other  words,  in  the  former  instance  ordinary 
radiation  cannot  be  augmented  so  well  by  a  loss  of  heat  in  the  form  of 
bound  heat.  In  this  regard,  the  cold-blooded  terrestrial  animals  have 
the  advantage,  because  they  are  able  to  bm-row  underground  or  to 
(five  under  water  to  increase  their  evaporation.  Very  similar  condi- 
tions exist  in  the  plants,  because  any  rise  in  the  external  temiuMature 
increases  their  transpiration,  thereby  lowering  their  own  temperature 
much  below  that  of  the  atmosphere.  This  protects  them  against  dry- 
1  Kunkel,  Zeitschr.  fiir  Biol.,  xxv,  1889,  69. 


1096  ANIMAL    HEAT 

ing.  In  animals  an  extreme  drop  in  their  body-temperature  may  be 
produced  by  exposing  them  to  cold  air  or  water.  Owing  to  the  reduc- 
tion in  the  warmth  of  the  tissues  then  ensuing,  the  nerve  centers  soon 
lose  their  irritability,  which  condition  in  turn  gives  rise  to  paralyses 
of  motion  and  sensation.  While  it  is  difficult  to  give  a  precise  lower 
limit,  recovery  has  been  noted  in  persons  whose  body-temperature  had 
been  reduced  to  24°  C. 

As  far  as  the  minor  fluctuations  are  concerned,  it  should  be  noted 
first  that  the  body-temperature  of  children  is  higher  than  that  of  adults, 
amounting  to  37.8°  C.  at  birth  and  to  36.8°  C.  shortly  afterward. 
Within  the  succeeding  24  hours,  however,  the  heat-regulatory  mech- 
anism becomes  functional  and  the  temperature  rises  to  37.5°  C. 
Between  puberty  and  the  age  of  forty  it  remains  at  37.1°  C.  A  slow 
decline  then  sets  in  until  about  the  seventieth  year,  when  it  again  rises. 
The  diurnal  variations  in  the  body-temperature  are  closely  allied  to 
the  changes  in  the  intensity  of  the  metabolism,  being  lowest  at  about 
5  o'clock  in  the  morning  and  highest  at  about  6  or  7  o'clock  in  the 
evening.  Besides,  they  may  be  greatly  modified  by  the  occupation 
of  the  individual.  Thus,  they  are  commonly  reversed  in  persons 
who  follow  their  vocation  at  night  and  sleep  during  the  day.  After 
meals  the  body-temperature  is  somewhat  higher  than  normal,  owing  to 
the  increased  glandular  activity  and  peristalsis,  as  well  as  to  the  heat 
liberated  by  the  food.  Iced  drinks  and  cold  food,  on  the  other  hand, 
abstract  heat  from  the  body  and  tend,  therefore,  to  cause  a  slight 
reduction,  if  used  in  large  amounts.  An  insufficient  intake  of  food 
lowers  the  temperature  because  it  tends  to  lessen  metabolism.  Any 
one  of  these  changes,  however,  rarely  amounts  to  more  than  0.2  or 
0.3°  C.  and  does  not  last  long. 

It  is  a  matter  of  common  experience  that  muscular  exercise  affects 
the  body-temperature  in  a  very  decisive  manner.  Thus,  even  such 
relatively  slight  efforts  as  are  required  to  play  a  game  of  tennis,  suffice 
to  raise  it  a  degree  or  two  above  normal,  but  inasmuch  as  this  activity 
invariably  increases  the  bloodflow,  this  superfluous  amount  of  heat  is 
soon  dissipated.  During  the  summer,  the  njean  body-temperature 
exceeds  the  normal  by  as  much  as  0.5°  C,  and  even  the  ordinary 
changes  in  the  outside  temperature  occurring  in  the  course  of  a  day, 
may  vary  the  body-temperature  by  several  tenths  of  a  degree.  Much 
more  decisive  changes  follow  the  immersion  of  the  body  in  warm  or 
cold  water.  ^  Those  mammals  which  at  the  approach  of  winter  enter 
the  state  of  hibernation,  suffer  a  constant  loss  of  heat  until  their 
temperature  has  reached  a  level  only  slightly  above  that  of  the  sur- 
rounding atmosphere.  Evidently,  this  effect  depends  in  large  part 
upon  a  lessened  heat-production  brought  about  by  a  reduction  in 
their  bodily  activities.  Upon  awakening  in  the  spring,  their  tempera- 
ture frequently  mounts  very  rapidly  in  complete  correspondence  with 
the  rather  sudden  resumption  of  their  active  life.     Drugs  affect  the 

1  Dill,  British  Med.  Jour.,  1890. 


THE    PRODUCTION    AND    DISSIPATION    OF    HEAT  1097 

body-temperature  in  different  ways.  Sucli  agents  as  alcohol  lower 
it,  because  they  stunulate  the  circulation  and  dilate  the  peripheral 
blood-vessels.  Both  these  changes,  therefore,  favor  heat-dissipation. 
The  anesthetics  and  narcotics  also  lower  it,  because  they  depress 
the  oxidations  and  relax  the  blood-vessels.  Strychnin,  cocain  and 
nicotin  increase  it. 

The  Regulation  of  the  Body-temperature.  Thermotaxis. — The 
mere  fact  that  the  honioiothernial  animals  are  able  to  retain  a  rather 
uniform  temperature  in  spite  of  their  inconstant  rate  cjf  heat-produc- 
tion and  almost  incessant  variations  in  the  surrounding  medium, 
proves  beyond  a  doubt  that  they  must  be  in  possession  of  a  mechanism 
whereby  their  body-temperature  is  regulated.  Clearly,  a  constant 
body-temperature  can  onl}'  be  obtained  if  the  dissipation  and  pro- 
duction of  heat  are  accurately  balanced,  and  hence,  any  change  there- 
in must  show  that  one  of  these  factors  is  more  powerful  than  the 
other.  Thus,  a  rise  in  the  body- temperature  may  be  due  either  to  a 
greater  heat-production  or  to  a  diminished  dissipation,  or  both. 
Quite  similarly,  a  lowering  of  the  bod3'-temperature  may  arise  either 
in  consequence  of  a  lessened  heat-production  or  an  increased  heat- 
dissipation,  or  both.  In  many  cases,  however,  it  is  quite  impossible 
to  state  definitely  which  of  these  two  factors  is  at  fault  unless  the 
fundamental  cause  of  the  variation  is  known.  Thus,  it  is  commonly 
held  that  fever  is  due  to  a  greater  production  of  heat,  although  it 
will  be  shown  later  on,  that  the  heat-dissipating  mechanism,  consisting 
of  the  vasomotor  apparatus  and  the  sweat-glands,  is  also  deranged  at 
this  time. 

It  will  be  seen,  therefore,  that  living  animals  behave  very  differ- 
ently from  dead  animals,  because  the  latter  absorb  and  lose  heat 
somewhat  in  the  manner  of  inorganic  bodies  It  is  a  matter  of  common 
observation  that  inanimate  material  may  be  artificially  warmed  and 
cooled  in  accordance  with  its  thermotactic  properties.  The  plants 
occupy  an  intermediate  position,  because  they  possess  certain  quali- 
ties which  allow  them  in  a  slight  measure  to  resist  outside  thermic 
influences. 

Heat-production.  Thermogenesis. — Heat  is  a  form  of  energy. 
It  is  not  matter,  but  merely  a  peculiar  state  of  matter,  because,  in 
accordance  with  the  undulatory  theory,  the  heat  of  a  body  is  due  to 
an  extremely  rapid  oscillation  or  vibration  of  its  molecular  constituents. 
Now,  since  heat-rays  occur  free  in  nature,  it  is  only  natural  to  suppose 
that  animals  must  receive  some  of  this  energy  in  the  form  of  ordinary 
radiations  from  the  sun  or  from  artificial  media.  The  chief  and  ulti- 
mate source  of  heat,  however,  lies  in  the  potential  energy  of  the  food 
and,  in  a  slight  measure,  also  in  hydrolytic  cleavage.  In  this  connec- 
tion attention  should  again  be  called  to  the  fact  that  the  thermogenic 
power  of  the  tissues  differs  greatly  in  accordance  with  their  physiolog- 
ical purpose  as  well  as  with  the  state  of  their  activity.  Now,  since 
muscular  exercise  leads  to  the  evolution  of  a  large  amount  of  heat,  it 


1098  ANIMAL   HEAT 

may  justly  be  concluded  that  muscular  rest  must  lessen  its  production, 
although  it  can  never  stop  it  altogether.  For  similar  reasons  it  may 
be  assumed  that  paralyzed  muscle  must  liberate  only  a  very  slight 
amount  of  heat,  a  fact  which  full}^  accounts  for  the  coldness  of  these 
parts  as  well  as  for  the  feeling  of  chilliness  experienced  by  the  para- 
lytic person.  It  is  true,  however,  that  in  these  cases  the  circulatory 
system  is  by  no  means  performing  its  function  properly  so  that  the 
factor  just  mentioned  is  usually  augmented  by  a  greater  loss  of  heat. 
An  experiment  directly  bearing  upon  this  question,  is  the  following: 
If  a  rabbit  is  curarized  and  is  kept  alive  by  artificial  respiration,  any 
alteration  in  the  temperature  of  the  atmosphere  changes  its  body- 
temperature  very  markedly  in  the  same  direction.  Since  this  agent 
paralyzes  the  motor  plates  of  the  muscles,  it  nullifies  the  action  of  the 
most  efficient  heat-producing  organ  of  the  body  and  permits  the  entire 
system  to  become  more  fully  dominated  by  outside  influences. 

The  beneficial  effect  of  muscular  activity  is  also  betrayed  by  the 
phenomenon  of  shivering,  an  involuntary  reaction  following  an  undue 
drop  in  the  body-temperature.  The  object  of  this  quivering  is  to 
produce  heat  to  counterbalance  the  loss.  If  this  is  not  sufficient, 
this  reflex  reaction  is  augmented  by  voluntary  muscular  contractions 
and  mechanical  impacts,  the  purpose  of  which  is  to  augment  the  circu- 
lation. The  efficiency  of  this  reflex  mechanism  is  also  betrayed  by 
the  changes  resulting  in  the  metabolism  of  the  warm-blooded  animals 
in  consequence  of  variations  in  the  temperature  of  the  atmosphere. 
Thus,  it  is  a  well-known  fact  that  low  temperatures  increase  and  high 
temperatures  decrease  the  metabolism  and  hence,  also  the  production 
of  heat.  During  the  cold  seasons  of  the  year  we  are  much  more  active. 
We  eat  more  and  gain  in  weight  perceptibly,  because  a  certain  pro- 
portion of  the  excess  material  is  stored.  In  hot  weather,  on  the  other 
hand,  we  are  slack  and  incline  to  rest  and  sleep  to  lessen  the  production 
of  heat. 

Cold  and  warm  baths  possess  a  similar  influence,  the  immersion 
of  the  body  in  water  of  32  to  34°  C.  for  a  minute  or  two  sufficing  to 
increase  the  output  of  carbon  dioxid  considerably.  This  change, 
however,  appears  only  if  the  person  is  in  tonus  and  does  not  counter- 
act this  reflex  reaction  by  remaining  passive  and  willfully  relaxing 
his  muscles.  In  the  latter  case,  the  carbon  choxid  output  would  be 
decreased,  causing  the  body-temperature  to  drop.  Furthermore,  this 
drop  need  not  always  become  apparent  immediately;  in  fact,  since 
the  cooled  external  parts  must  slowly  replenish  the  heat  which  they 
have  lost  at  the  expense  of  the  internal  structm'es,  from  15  to  20  min- 
utes may  elapse  before  it  is  experienced.  As  soon,  however,  as  the 
subcutaneous  parts  have  regained  their  heat,  the  rectal  temperature 
returns  rapidly  to  normal.  This  process  of  equalization  may  be 
greatly  hastened  by  voluntary  muscular  contractions  as  well  as  by 
deep  and  superficial  massage.  Another  means  of  varying  the  pro- 
duction of  heat  lies  in  the  character  of  the  food  ingested.     Thus,  the 


THE    PRODUCTION    AND    DISSIPATION    OF   HEAT  1099 

person  who  restricts  his  (Het  to  carbohydrates  in  summer  and  to  meat 
and  fat  in  winter  unconsciously  proves  that  the  heat  of  combustion  of 
the  former  is  low  and  that  of  the  latter  high.  This  fact  is  illustrated 
further  by  the  differences  in  the  character  of  the  food  of  the  inhabitants 
of  the  northern  and  soutliern  countries,  the  oily  and  fatty  food  of  the 
far  north  being  relished  mainly  on  account  of  its  high  heat  value.  The 
influence  of  muscular  contraction  is  elucidated  further  by  the  fact 
that  very  high  temperatures  are  frequently  encountered  in  tetanus 
and  the  status  epilepticus.  In  addition,  MacCullum^  states  that  high 
temperatures  are  always  noted  in  dogs  when  suffering  from  spasms 
following  parathyroidectomy.  Moreover,  since  these  convulsions 
may  be  stopped  by  the  administration  of  calcium  acetate,  this  salt 
likewise  reduces  their  body-temperature.  These  and  other  phe- 
nomena which  might  still  be  mentioned,  show  very  clearly  that  the 
production  of  heat  is  controlled  by  involuntary  and  voluntary  im- 
pulses involving  the  different  tissues,  chiefly  the  muscles. 

Heat-dissipation.  Thermolysis, — An  animal  loses  its  heat  in 
two  ways,  namely,  by  radiation  or  conduction  from  its  skin  and  mucous 
surfaces,  and  in  the  form  of  bound  or  latent  heat  in  its  different  fluid 
and  semi-solid  excreta.  The  channels  which  take  part  in  this  dissipa- 
tion are  the  skin,  pulmonary  tract,  alimentary  canal  and  urinary 
passage.  From  the  skin  heat  is  lost  by  radiation,  conduction  and  con- 
vection as  well  as  in  the  form  of  bound  heat  in  its  secretions,  the  sweat 
and  sebaceous  material.  The  pulmonary  passage  transfers  heat  to  the 
inspired  air  both  directly  as  well  as  in  the  watery  particles  which  are 
added  to  the  expiratory  air.  The  alimentar}-  canal  discharges  a 
certain  amount  of  heat  in  the  feces  and  also  imparts  some  of  it  to  the 
food  when  taken  into  the  mouth  and  stomach.  Obviously,  the  tem- 
perature of  the  latter  must  be  raised  to  that  of  the  body.  The  urinary 
tract  gives  off  a  certain  amount  of  latent  heat  in  the  urine. 

Under  ordinary  conditions  by  far  the  greatest  loss  of  heat  occurs 
through  the  skin  and  its  appendages.  Furthermore,  since  the  inten- 
sity of  radiation  depends  upon  the  nature  of  the  surface  as  well  as  upon 
the  excess  of  temperature  of  the  radiating  surface  over  that  of  the  sur- 
rounding medium,  it  will  be  evident  that  the  uncovered  areas  of  the 
skin  must  discharge  a  greater  amount  of  heat  than  those  protected 
by  hairs  or  clothing.  In  addition,  it  is  to  be  noted  that  the  more 
vascular  regions,  such  as  the  forehead,  radiate  more  heat  than  the  less 
vascular  ones,  such  as  the  lobules  of  the  ears  or  the  tip  of  the  nose. 
In  either  case,  however,  the  loss  of  heat  maj'  be  increased  by  moving 
about  or  bj^  setting  up  currents  in  the  surrounding  air,  because  these 
procedures  tend  to  augment  the  difference  in  the  temperatures  of  the 
radiating  surface  and  the  absorbing  medium. 

In  measuring  the  radiating  heat  we  make  use  of  an  instrument 
which  is  constructed  after  the  principle  of  the  resistance  thermometer 
and  is  known  as  the  resistance  radiometer  or  bolometer.     It  consists  of 

1  Harvey  Lectures,  New  York,  1908-09. 


1100  ANIMAL    HEAT 

a  grating  of  lead-paper  or  tinfoil  which  is  arranged  vertically  in  a 
closed  box  to  protect  it  from  air-currents.  When  the  observation  is 
to  be  made,  the  lid  is  removed  from  this  box  and  the  absorbing  medium 
is  adjusted  at  a  definite  distance  from  the  skin.  About  1725  calories 
are  lost  by  the  skin  which  corresponds  to  a  loss  of  69  per  cent,  of  the 
total,  provided  the  latter  is  estimated  at  2500  calories  for  each  24 
hours.  The  quantity  of  water  evaporated  from  the  skin  may  be  esti- 
mated at  660  grm.  in  24  hours.  Since  0.582  calorie  are  needed  to  con- 
vert each  gram  of  water  into  vapor,  about  381  large  calories  are  lost  in 
this  way.  This  corresponds  to  a  loss  of  15.3  per  cent.,  making  a  total 
for  the  skin  of  about  85  per  cent,  of  the  entire  heat  dissipation. 

The  quantity  of  water  evaporated  from  the  puhnonary  passage, 
is  estmiated  at  400  grm.  As  each  gram  requires  0.582  calorie  to  con- 
vert it  into  vapor,  the  total  loss  effected  through  this  channel  amounts 
to  about  232  calories,  or  9.4  per  cent,  of  the  total.  An  additional 
3.8  per  cent,  is  apportioned  to  the  inspiratory  air  to  warm  it  to  the 
temperature  of  the  body.  The  remaining  loss  is  covered  by  the  warm- 
ing of  the  food  and  drink  upon  its  entrance  into  the  body,  and  by  the 
loss  suffered  upon  its  subsequent  discharge  from  the  body  in  the  fonn 
of  feces  and  urine.  Estimated  at  3  kilos  with  an  initial  average  tem- 
perature of  12°  C,  about  60  calories  are  dissipated  in  this  way.  This 
indicates  a  loss  of  2.8  per  cent,  of  the  total. 

The  many  factors  which  may  vary  the  intensity-  of  heat-dissipation 
may  conveniently  be  classified  as  involuntary  and  voluntary.  Among 
the  former  are  to  be  mentioned  those  reflexes  which  give  rise  to  vaso- 
motor, pilomotor  and  secretomotor  reactions.  It  is  a  matter  of 
every  day  experience  that  the  skin  and  subcutaneous  tissues  pale  under 
the  influence  of  cold  and  flush  under  the  influence  of  warmth.  These 
changes  indicate  that  cold  constricts  the  cutaneous  blood-vessels  and 
drives  the  blood  into  the  deeper  parts  of  the  body  in  an  endeavor  to 
diminish  heat-dissipation.  Warmth,  on  the  other  hand,  relaxes  these 
vessels  and  allows  a  more  rapid  escape  of  the  body-heat.  In  the  first 
case,  thermoh'sis  is  also  hindered  in  a  varying  measure  by  the  secretion 
of  the  sebaceous  glands,  which  the  northern  people  carefully  preserve 
and  augment  by  anointing  their  body  with  oil  and  lard.  Quite 
smiilarh",  the  aquatic  annuals  are  in  possession  of  special  glands  v\-hich 
serve  the  purpose  of  covering  their  body  with  a  fatty  secretion.  The 
function  of  the  latter  is  to  diminish  friction  and  to  protect  them  more 
thoroughly  against  an  undue  loss  of  heat.  Upon  this  basis  rests  the 
practice  of  s«'immers  to  anoint  their  skin  with  fatt}^  substances.  In 
the  second  case,  the  dissipation  of  heat  maj'  be  greatly  facilitated  by 
moistening  the  bodj' -surface  with  the  secretion  of  the  sweat-glands. 
In  this  way,  a  large  part  of  the  heat  is  lost  in  the  form  of  latent  or 
bound  heat,  and  naturally,  the  higher  the  outside  temperature  and  the 
dr\^er  the  air,  the  more  rapid  must  be  the  evaporation  and  loss  of  heat. 
Contrariwise,  a  warm  but  humid  atmosphere  prevents  the  evaporation 
of  the  sweat  and  dissipation  of  heat.     It  is  this  secretomotor  mechan- 


THE    PRODUCTION    AND    DISSIPATION    OF    HEAT  1101 

ism  which  allows  us  to  endure  temperatures  above  that  of  the  blood 
for  days  and  even  permits  us  to  expose  ourselves  for  a  brief  period  of 
time  to  t(>mperatures  above  that  of  boiling  water. 

While  the  amount  of  latent  heat  discharged  by  way  of  the  respira- 
tory  tract,  is  inconsiderable  in  man,  this  channel  serves  practically  as 
the  only  means  of  thermolysis  in  many  animals.  This  is  especially 
true  of  those  whose  bodies  are  covered  with  thick  fur  which  in  itself 
hinders  radiation.  Thus,  we  note  that  the  dog  pants  whenever  a 
more  copious  loss  of  heat  is  made  necessary.  The  respiratory  air  is 
then  made  to  oscillate  back  and  forth  across  the  moistened  mucous  sur- 
faces, and  some  bound  heat  is  also  lost  in  the  fluid  which  dripples  out  of 
the  corners  of  his  mouth.  At  the  approach  of  winter,  these  animals  most 
generally  acquire  an  even  thicker  coat  of  fur  as  well  as  more  considerable 
amounts  of  subcutaneous  fat.  The  value  of  the  latter  as  a  conserver 
of  heat  is  well  illustrated  by  the  fact  that  water-fowls  and  especially 
those  inhabiting  very  cold  waters,  are  abundantly  supplied  with  it. 
Moreover,  since  women  are  usually  more  copiously  equipped  with 
adipose  tissue,  they  are  in  a  better  position  to  withstand  cold  than  men. 
Heat  may  also  be  conserved  by  bringing  the  legs  and  arms  in  apposition 
with  the  trunk,  because  in  this  position  a  smaller  area  of  the  body  is 
exposed  to  the  surrounding  medium.  The  opposite  effect  is  produced 
by  exposing  the  flanks  more  fully  to  the  medium,  a  common  practice 
among  rabbits  and  dogs  on  warm  summer  days. 

Among  the  voluntary  factors  controlling  the  loss  of  heat,  might  be 
mentioned  the  selecting  and  fitting  out  of  the  winter  quarters  of  the 
hibernating  animals,  the  building  of  nests,  the  adaptation  of  the  dwell- 
ings of  man  to  outside  conditions,  the  wearing  of  clothing,  and  man}' 
others.  The  value  of  clothes  lies  in  the  fact  that  they  hinder  the  free 
circulation  of  the  air.  Inasmuch  as  this  medium  is  by  no  means 
a  good  conductor  of  heat,  they  retard  the  escape  of  radiant  heat  from 
the  skin  and  become  warm  by  absorption.  This  process  is  repeated 
at  every  successive  layer  of  clothing,  because  each  layer  acts  as  a 
concentric  air-jacket  which  tends  to  conserve  the  heat  stored  up  in 
the  water  vapor  right  next  to  the  skin.  But  the  thickness  of  the 
clothing  is  not  everything  and  attention  must  also  be  paid  to  its 
quality,  inclusive  of  its  porosity,  weight,  color  and  conducting  power. 
Cotton  and  linen  are  good  conductors  and,  therefore,  allow  the  heat 
to  escape  more  readily.  Wool  possesses  the  opposite  qualities  and 
is  better  adapted  for  cold  weather.  Besides,  it  is  markedly  hygro- 
scopic and  prevents  a  too  rapid  evaporation  of  the  moisture  and  chilling 
of  the  body.  The  coarser  the  material,  the  greater  its  radiating  power, 
and  the  cooler  the  clothing  made  from  it.  Furthermore,  black  cloth- 
ing is  warmer  than  white  clothing,  because  it  possesses  a  greater  heat 
absorbing  power.  During  sleep,  when  the  metabolism  and  ther- 
mogenetic  function  of  the  tissues  is  at  low  ebb,  extra  covers  are  needed 
to  prevent  an  undue  loss  of  heat. 


1102  ANIMAL   HEAT 

The  Nervous  Mechanism  Regulating  Thermotaxis. — Technically 
heat-production  is  designated  as  thermogenesis,  heat-dissipation  as 
thermolysis,  and  the  relationship  between  these  two  factors  as  thermo- 
taxis. The  question  concerning  the  part  which  the  nervous  system 
plays  in  thermotaxis,  cannot  be  answered  with  certainty.  We  have 
previously  seen  that  reflexes  producing  vasomotor  and  secretomotor 
changes,  are  constantly  at  play,  and  hence,  it  must  be  concluded  that 
the  central  nervous  system  is  closely  concerned  with  heat-regulation. 
Thus,  we  find  that  the  infant  does  not  acquire  this  function  until 
some  time  after  birth,  while  other  animals,  such  as  the  guinea-pig 
and  chick,  already  possess  it  when  the}^  are  born.  In  other  words, 
thermotaxis  follows  a  course  parallel  to  that  of  the  development  of  the 
nervous  system,  and  this  must  necessarily  be  so,  because  the  striated 
and  smooth  muscle  tissues  and  sweat-glands  must  first  obtain  their 
innervation  before  they  can  be  in  a  position  to  influence  the  bodj-tem- 
perature.  Some  doubt,  however,  still  exists  regarding  the  presence 
of  separate  heat-centers  and  heat-nerves.  For  all  that  mattrs, 
every  motor  nerve  of  skeletal  muscle  maj^  really  be  regarded  as  a  heat- 
nerve  and  every  nucleus  as  a  heat-center,  because  the  impulses 
generated  by  them  not  only  influence  muscular  activity  but  also 
their  production  of  heat.  Consequently,  the  condition  existing  here, 
is  very  similar  to  that  previously  observed  in  the  case  of  the  trophic 
nerves,  when  we  came  to  the  conclusion  that  the  nutritive  state  of  a 
tissue  is  dependent  upon  the  ordinary  motor  impulses  relegated  to  it, 
and  not  upon  separate  impulses  of  a  purely  trophic  kind. 

Many  observers  have  found  that  injuries  to  various  parts  of  the 
cerebral  cortex,  basal  ganglia,  and  medulla  give  rise  to  changes  in  the 
body-temperature.  Thus  Krehl,  Ott,^  Reichert,-  and  others,  have 
noted  that  the  transverse  division  of  the  corpora  striata  invariably  pro- 
duces a  pronounced  rise  in  the  body-temperature  (110°  F.)  and  death. 
Other  heat-accelerator  centers  have  been  localized  in  the  tuber  cinereum, 
cruciate  sulcus,  and  the  juncture  of  the  suprasylvian  and  postsylvian 
fissures.  Heat-inhibitory  centers  have  been  localized  in  the  medulla 
and  region  of  the  pons.  The  evidence  at  our  disposal,  however,  is 
too  meager  to  warrant  definite  conclusions,  because  many  errors  have 
undoubtedly  crept  in  on  account  of  the  character  of  the  methods 
wliich  must  necessarily  be  practised  in  experiments  of  this  kind.  The 
latter  consist  in  the  destruction  of  parts,  transection  of  paths,  cauter- 
ization and  puncture.  Secondly,  it  is  very  possible  that  the  results 
of  these  procedures  are  dependent  in  a  large  measure  upon  disturbances 
of  the  vasomotor  (tuber  cinereum)  and  musculomotor  mechanisms 
(medulla),  and  not  upon  a  derangement  of  the  function  of  true  heat- 
centers. 

^  Jour.  Nerv.  and  Mental  Dis.,  1884. 

2  Univ.  Penna.  Med.  Magazine,  1894;  also  White,  Jour,  of  Physiol.,  xii,  1891, 
233;  Tangl,  Pflliger's  Archiv,  1895;  and  Sachs  and  Green,  Am.  Jour,  of  Physiol., 
xlii,   1917,  603. 


THE    PRODTTCTION    AND    DISSIPATION    OF    HEAT  1103 

The  Total  Quantity  of  Heat. — The  total  quantity  of  heat  liberated 
by  an  anhnal  is  luscertaincd  (a)  by  determining  the  heat  values  of  the 
different  foodstuffs  ingested  by  the  nietliod  of  direct  oxidation,  and 
(6)  by  measuring  the  heat  evolved  by  it  with  the  help  of  the  water  or 
air-calorimeter.  But  whether  reduced  into  its  constituents  in  a 
bomb-caloruneter  or  more  slowly  burned  in  the  body,  the  food  yields 
the  same  amount  of  heat,  jirovided  it  is  fully  consumed  and  is  not 
allowed  to  discharge  its  energy  as  work.  A  plant  exposed  to  sunlight, 
combines  carbon  dioxid  and  water  into  sugar,  while  oxygen  is  given 
off  and  heat  is  absorbed.  Now,  if  1  grm.  of  sugar  is  placed  in  a 
steel  receptacle  (Berthelot)  into  which  oxygen  is  passed  under  a  pres- 
sure of  450  lbs.  to  the  square  inch,  the  combustion  of  this  substance 
may  be  incited  by  an  electric  spark.  ^  It  will  then  be  found  to  have 
yielded  carbon  dioxid  and  water  and  an  amount  of  heat  equal  to  that 
absorbed.  The  latter  is  determined  by  immersing  the  steel  receptacle 
in  a  liter  of  water.  On  determining  the  temperature  of  this  water  by 
means  of  a  thermometer,  it  will  be  noted  that  it  has  risen  3.755°  C. 
during  this  combustion.  It  may  then  be  said  that  1  grm.  of  sugar 
furnishes  3.755  calories  of  heat,  because  1  calorie  is  the  quantity  of 
heat  required  to  raise  1  kilogram  (1  liter)  of  water  1°  C.  This  method 
of  absolute  reduction  in  the  bomb-calorimeter  has  also  been  applied  to 
a  large  number  of  other  food  substances  with  the  following  results: 

Animal  fat 9 .  500  calories  Casein 5 .  867  calories 

Butter 9.231  calories  Egg  albumin 5.735  calories 

Olive  oil 9.489  calories  Beef 5.640  calories 

Glycerin 4.317  calories  Veal 5.662  calories 

Elastin 5 . 961  calories  Albumins 5.711  calories 

The  different  carbohydrates  have  yielded  the  following  heat  values : 

Dextrose 3 .  742         Maltose 3 .  949 

Levulose 3.755         Starch 4.182 

Galactose 3.721         Dextrin 4.112 

Cane  sugar 3 .  955         Cellulose 4 .  185 

Milk  sugar 3.951 

From  these  figures  Rubner-  has  deduced  the  following  "standard"  values: 

1  gram  of  protein 4.1  calories 

1  gram  of  carbohydrate 4.1  calories 

1  gram  of  fat 9.3  calories 

These  values,  however,  are  physical  values  and  represent  the  heat 
evolved  by  them  when  completely  oxidized  to  carbon  dioxid  and 
water.  In  the  animal  body  these  substances  are  not  always  thoroughly 
utilized  and  hence,  their  nutritive  value  may  not  correspond  precisely 
with  these  figures.  This  is  true  in  particular  of  the  proteins,  because 
in  the  bomb-calorimeter  the  nitrogen  of  these  substances  is  converted 
into  nitric  acid,  while  in  Ihe  body  they  are  oxidized  to  urea.     Conse- 

1  Schlossmann,  Zeitschr.  fiir  phys.  Chemie,  xxxvii,  1903,  324. 

2  Zeitschr.  ftir  Biol.,  xlii,  1901,  261;  also:  Atwater,  Am.  Jour,  of  Physiol.,  x, 
1904,  30. 


1104  ANIMAL    HEAT 

quently,  the  heat  hberated  by  the  proteins  in  the  body  is  less  than  that 
obtained  when  they  are  burned  in  the  bomb-calorimeter.  The 
carbohydrates  and  fats,  on  the  other  hand,  are  reduced  to  carbon 
dioxid  and  water  and  produce,  therefore,  practically  as  much  heat 
in  the  body  as  when  oxidized  in  the  bomb.  In  the  latter  case,  the 
discrepancy  amounts  to  only  3  per  cent,  and  is  dependent  upon  the 
fact  that  some  portions  of  these  substances  escape  unutilized  into  the 
feces.  In  the  case  of  the  proteins,  on  the  other  hand,  this  loss 
amounts  to  20  or  25  per  cent,  which  is  caused  in  part  by  their  entrance 
into  the  feces  (1.0  to  1.3  per  cent.)  and  in  part  by  their  incomplete 
reduction  into  urea.  But  as  this  compound  may  be  further  split 
up  in  the  bomb  to  carbon  dioxid  and  water  under  liberation  of  heat, 
it  becomes  necessary  to  deduct  this  amount  of  heat  from  that  obtained 
during  their  physical  combustion.  According  to  Rubner,  1  grm.  of 
urea  yields  2.523  calories;  moreover,  since  this  amount  of  urea  re- 
quires the  oxidation  of  3  grm.  of  protein,  the  amount  of  heat  to  be 
deducted  from  the  heat-value  of  protein  substance  is  0.841  calorie. 
This  loss,  together  with  that  incurred  by  the  escape  of  protein  into  the 
feces,  reduces  the  physiologic  heat-value  of  this  foodstuff  to  about 
4.124  calories.^ 

The  experiments  of  Voit  and  Rubner  upon  dogs  have  shown  a  very 
close  correspondence  between  the  heat  values  of  the  different  foodstuffs 
calculated  in  the  above  manner  and  those  obtained  in  the  calorimeter. 
These  results  are  fully  upheld  by  the  determinations  of  the  heat-pro- 
duction in  normal  men  under  different  conditions  of  life.  Thus,  it 
has  been  found  that  the  basal  value  in  an  adult  weighing  70  kilos  (156 
pounds) ,  is  70  calories  in  1  hour  or  1 .680  calories  in  24  hours.  This  term 
of  basal  heat-production,  however,  signifies  that  the  person  has  received 
no  nourishment  during  the  preceding  15  hours  and  has  continued  to 
rest  in  bed  after  a  night  of  sleep.  If  any  food  has  been  taken  during 
this  period,  about  168  calories  should  be  added  to  this  total,  which 
makes  1 .848  calories  in  all.  Exercise  increases  this  value  very  materi- 
ally, and  naturally,  this  increase  must  be  compensated  for  by  a  larger 
intake  of  food.  According  to  the  experiments  of  Atwater  and  Bene- 
dict, ^  the  efforts  connected  with  arising  and  sitting  in  a  chair  increases 
the  basal  heat-production  by  8  per  cent,  and  the  ordinary  movements 
performed  by  us  in  the  course  of  a  day,  by  20  per  cent.,  thus: 

Night 616  calories 

Day 1 .552  calories 

Total 2.168  calories 

A  man  of  medium  weight,  leading  a  sedentary  life,  requires  320  calories 
in  addition  to  these  2.168,  or  2.500  calories  in  all,  in  order  to  supply  him 

1  Rubner,  Die  Gesetzedes  Energieverbrauchs.,  1902,  also:  Calorim.  Methodik, 
Marburg,  1891. 

2  Ergebn.  der  Physiol.,  iii,  1904. 


THE    PH01)T"(TI0N    AND    DISSIPATION    OF    HEAT  1105 

with  sufficient  fuel  (o  curry  on  even  the  most  niodenito  muscular 
activity.'  Be^-ond  this  ordinary  hcal-produclion,  tlie  amount  of  fuel 
needotl  by  a  person  is  in  agreement  with  the  character  of  the  exercise. ^ 
Farmers  require  on  an  average  3500  calories  and  six-day  bicycle  riders 
10,000  calories  per  day.  Boj^s,  on  the  other  hand,  need  only  about 
1500  caloi-ics,  ;in(l  hal)ies  100  calories  foi-cacli  Icilo^rani  of  body  weight. 
The  Effect  of  Varnishing  the  Skin  and  Other  Procedures. — The 
larger  the  surface  of  the  body  exposed  to  the  cooler  medium,  the  greater 
must  be  the  loss  of  heat.  Consequently,  since  a  small  animal  presents 
a  proportionately  larger  surface;  to  th(;  surioundings  in  relation  to  its 
mass  than  a  large  animal,  its  loss  of  heat  nuist  exceed  that  of  the  latter. 
Obviously,  this  more  considerable  thermolysis  must  be  accurately 
balanced  by  a  greater  thermogenesis,  and  hence,  the  smaller  animal 
must  possess  a  more  intense  metabolism.  This  is  evinced  by  its  more 
rapid  respiratory  and  cardiac  rates. 

While  warm-blooded  animals  may  survive  a  brief  exposure  to  an  outside 
temperature  of  from  100°  to  132°  C,  owing  to  the  profuse  loss  of  latent  heat  then 
ensuing,  cold-blooded  animals  are  usually  killed  at  about  40°  C,  because  their 
musculature  enters  at  this  temperature  the  state  of  rigor  caloris.  Insects  commonly 
withstand  a  temperature  of  6-4°  C.  Even  the  ordinary  temperature  of  a  beehive 
varies  between  30°  and  40°  C.  which  represents  stagnated  heat  produced  by  the 
bees  themselves.  Plants  wither  at  a  temperature  of  52°  C.  If  left  to  themselves, 
warm-blooded  animals  visually  do  not  survive  when  their  body-temperature  has 
been  reduced  to  20°  C,  but  if  artificial  respiration  and  warmth  are  applied  to  them, 
they  may  recover  from  a  temperature  even  lower  than  the  one  just  given. 
Cold-blooded  animals  are  able  to  withstand  1°  C.  and  may  even  be  partially  frozen. ^ 

The  hibernating  animals  show  signs  of  depression  when  their  temperature  falls 
below  28°  C.  At  18°  C.  they  exhibit  a  decided  drowsiness,  at  6°  C.  semi-sleep  and 
at  1.6°  C.  deep  sleep."*  At  this  time,  the  heart  beats  only  8  to  10  times  in  a  minute, 
while  the  respiratory  movements  cease  altogether.  The  very  small  amount  of 
oxygen  which  they  now  require  is  obtained  by  means  of  the  volumetric  changes 
which  the  heart  undergoes  during  its  cycle.  On  systole  this  organ  becomes  smaller, 
causing  a  slight  amount  of  air  to  flow  into  the  lungs,  while  on  diastole,  it  becomes 
larger  and  forces  an  equal  amount  of  air  outward.  This  constitutes  the  so-called 
cardio-pneumatic  phenomenon.  When  the  hibernating  animal  awakes,  its  body- 
temperature  may  rise  as  much  as  20°  C.  in  the  course  of  two  hours.  ^ 

A  rise  in  temperature  may  also  result  directly  after  death.  Obviously,  this 
effect  must  be  produced  by  a  continued  heat-production  and  a  diminished  heat- 
dissipation,  establishing  a  balance  in  favor  of  the  former  process.  Thus,  it  may 
happen  that  the  sudden  cessation  of  the  circulation  prevents  the  escape  of  heat 
from  the  still  active  tissues.  A  most  favorable  condition  of  this  kind  is  created 
when  the  body-temperature  has  been  high  beforehand,  so  that  the  interrtiption  of 
heat-dissipation  may  allow  an  excessive  stagnation  of  heat  in  the  highly  active 
tissues.  Muscular  spasms  at  the  time  of  death  augment  this  effect.  Heat  is  also 
produced  during  the  fixation  of  the  muscles  coincident  with  the  onset  of  rigor  mortis. 

Covering  the  skin  with  a  layer  of  varnish  or  paraffin  has  the  same  effect  as  cooling, 
because  an  animal  so  treated  loses  heat  very  rapidly,  owing  to  the  dilated  condition 

^Lusk,  Science  of  Nutrition,  W.  B.  Saunders  and  Co.,  1909. 
2  Rumf,  Pfliiger's  Archiv,  xxxiii,  1884,  538,  and  Knoll,  Archiv  fur  Exp.  Path, 
und  Pharm,  xxxvi,  1895,  305. 

^Miiller-Erzbach.,  Zoolog.  Anz.,  1891. 
*  Merzbacher,  Ergebn.  der  Physiol.,  iii,  1904,  14. 
^  Pembrey,  Jour,  of  Physiol.,  xxix,  1903,  195. 
70 


1106  ANIMAL    HEAT 

of  its  cutaneous  blood-vessels.  ^  If  placed  in  a  warm  chamber  or  covered  with 
straw  or  blankets,  it  invariably  survives  the  critical  period  directly  after  the  appli- 
cation of  the  varnish,  because  later  on  the  hairs  grow  out  sufficiently  to  disengage 
the  varnish  from  tlie  skin,  allowing  the  latter  at  least  partially  to  protect  itself 
against  this  enforced  loss  of  heat.  The  view  that  this  procedure  prevents  the 
elimination  of  toxic  substances  through  the  skin,  has  not  found  experimental 
substantiation.  The  administration  of  nervous  depressants  most  generally  evokes 
a  loss  of  heat  against  which  the  patient  must  be  carefully  guarded.  Thus,  extra 
blankets  are  to  be  placed  upon  a  person  who  has  been  given  chloral. 

H3rperthermy  and  Hypothermy. — In  addition  to  the  variations  in 
the  body-temperatiirc  noted  in  the  course  of  the  previous  discussion, 
brief  reference  should  also  be  made  at  this  time  to  the  hyperthermy 
commonly  following  the  entrance  into  the  body  of  pathogenic  bacteria 
and  toxic  substances,  such  as  the  derivatives  of  fermentative  processes. 
This  condition  which  is  usually  designated  as  fever,  is  represented  by 
a  complex  of  symptoms  of  which  a  decided  and  rather  lasting  elevation 
of  the  body-temperature  is  the  most  characteristic.  Rises  to  38°  or 
39°  C.  are  usually  spoken  of  as  "low  fever  "  or  pyrexia,  and  rises  to  41°  C. 
as  ''high  fever"  or  hyperpyrexia.  Among  the  other  readily  recog- 
nizable signs  are  thirst,  painful  sensations,  weakness,  apathy,  nausea, 
vomiting,  alterations  in  the  quantity  and  quality  of  the  various  secre- 
tions and  excretions  of  the  body,  and  such  other  changes  as  may  be  more 
specifically  related  to  the  infection.  Fever  may  begin  gradually,  and 
more  abruptly  with  a  chill;  it  may  be  constant,  remittent  and  intermit- 
tent; it  may  last  a  variable  period  of  time  and  disappear  either  gradu- 
ally or  rather  suddenly.  In  every  case,  however,  it  represents  a  physi- 
ological attempt  on  the  part  of  the  body  to  correct  a  disturbance  of 
function,  and  hence,  it  is  quite  proper  to  refer  to  it  as  a  reaction. 

Fever  or  pyrexia  may  be  due  either  to  an  increased  production  or 
to  a  diminished  dissipation  of  heat,  or  both.  Evidently,  any  dispropor- 
tionality  between  these  two  factors  which  leaves  a  positive  balance  for 
heat,  must  bring  about  an  elevation  of  the  body-temperature.  Con- 
cerning the  first  factor,  we  have  the  positive  statements  of  Krauss,^ 
Nebelthau,^  May,"*  Staehelm,^  and  others  that  thermogenesis  is  in- 
creased during  fever,  the  difference  amounting  to  as  much  as  25  to  50 
per  cent.  Direct  calorimetric  determinations  have  also  proved  that 
the  loss  of  heat  is  increased  during  fever,  but  in  comparison  with  the 
the  enormous  production  of  heat,  the  dissipation  is  undoubtedly  dimin- 
ished. In  other  words,  the  heat  is  stagnated,  as  is  evinced  by  the 
livid,  blue  and  cold  character  of  the  skin  following  the  contraction  of 
the  cutaneous  blood-vessels  and  the  cessation  of  evaporation  from  the 
skin.  When  these  changes  first  occur,  a  sensation  of  cold  is  experi- 
enced which  causes  the  patient  to  draw  his  body  into  as  small  a  mass  as 
possible  and  to  cover  himself  thickly  with  blankets.     The  quivering 

1  Krieger,  Zeitschr.  fiir  Biol.,  1869;  also  Babak,  Pfliiger's  Archiv,  cviii,  1905,  389. 

2  Zeitschr.  fur  klin.  Med.,  xviii,  1890,  91. 

3  Zeitschr.  fiir  Biol.,  xxxi,  1894,  293. 
^  Ibid.,  XXX,  1893. 

6  Zeitschr.  fur  klin.  Med.,  Ixvi,  1904,  77. 


THE    PRODUCTION    AND    DISSIPATION    OF    HEAT  1107 

of  the  muscles  and  ftoose-flesli  appearing  at  t.liis  time  greatly  aid  in 
sending  the  body-tempei-aturc^  ujnvard.  The  height  of  the  fever 
having  been  attained,  heat-dissipation  more  nearly  balances  heat- 
production/  but  is  still  inadequate  to  allow  the  abnormally  large 
amounts  of  heat  to  escape.  During  the  last  stages  of  fever,  the  pro- 
duction of  heat  is  diminished,  while  tlie  dissipation  of  heat  gi-adually 
increases,  owing  to  the  reestablishment  of  a  projier  control  over  the 
capillaries  of  the  skin  and  the  reappearance  of  the  sweat. 

The  underlying  causes  of  fever  having  been  established,  the  ques- 
tion may  now  be  asked  how  these  changes  are  brought  about.  The 
two  most  acceptable  explanations  are  contained  in  the  so-called  neuro- 
genic and  toxogenic  theories  of  fever.  The  former  has  been  put  forth 
by  Liebermeister^  and  holds  that  the  heat  centers  regulating  the  body- 
temperature  are  raised  to  a  higher  pitch  during  fever,  simulating  our 
means  of  adjusting  the  regulator  of  a  thei-mostat  in  such  a  way  that 
the  latter  may  jdeld  a  temperature  of  40°  C.  instead  of  35°  C.  In 
accomplishing  this  end,  the  heat  centers  make  use  chiefly  of  the  vaso- 
motor and  secretomotor  mechanisms.  In  this  restricted  form  this 
theory  seems  to  have  little  in  its  favor,  but  naturally,  this  statement 
does  not  imply  that  the  ordinary  reflexes  are  excluded  as  adjunct 
causative  factors  in  the  production  of  this  form  of  hyperthermy.  In 
fact,  the  evidence  is  against  such  a  view,  because  the  brief  febrile 
reactions  following  the  passage  of  biliary  or  renal  calculi,  catheriza- 
tion,  and  various  operative  procedures,  are  undoubtedly  produced  by 
a  diminished  loss  of  heat  incited  by  the  reflex  constriction  of  the  cuta- 
neous blood-vessels.  Hirsch,  Miiller  and  Rolly^  have  put  forward  the 
view  that  fever  results  in  consequence  of  a  derangement  of  the  meta- 
bolic condition  of  the  tissue  cells  by  poisonous  substances.  This 
explanation  has  much  in  its  favor,  and  is  well  adapted  to  those  febrile 
reactions  which  follow  upon  the  entrance  of  pathogenic  bacteria  into 
the  system.  The  implication  is  that  the  cells  respond  to  these  sub- 
stances with  an  increased  activity/  thereby  endeavoring  to  accomplish 
some  beneficial  effect.  Since  the  intake  of  food  is  much  diminished 
at  this  time,  this  metabolic  augmentation  is  had  mainly  at  the  expense 
of  the  organized  constituents  of  the  body. 

The  preceding  conclusion  is  upheld  by  the  fact  that  fever  greatly 
affects  the  metabolism,  but  probably  not  so  much  its  intensity  as  the 
manner  in  which  it  involves  the  different  foodstuffs.  The  deduction 
that  it  is  not  merely  a  matter  of  intensity  of  oxidation,  is  upheld  by  the 
fact  that  the  amount  of  the  oxidation  products  derived  from  febrile  com- 
bustions is  very  small,  as  well  as  by  the  fact  that  the  respiratory  quotient 
remains  practically  unchanged.^     It   appears,   therefore,   that  these 

1  Krehl,  Zeitschr.  ftir  allg.  Physiol.,  i,  1902,  29. 

2  Pathologie  des  Fiebers,  1875. 

3  Deutsch.  Archiv  fiir  klin.  Med.,  Ixxv,  1903,  265. 
«  Roily  and  Meltzer,  ibid.,  xciv,  1908,  335. 

5  Senator  and  Richter,  Zeitschr.  fur  klin.  Med.,  lix,  1904,  16. 


11  OS  ANIMAL   HEAT 

disturbances  do  not  lie  in  the  oxidation  of  the  non-nitrogenous  sub- 
stances, but  rather  in  that  of  the  proteins.  Furthermore,  since  the 
intake  of  food  is  greatly  diminished  in  fever,  the  oxidations  must  go 
on  chiefly  at  the  expense  of  the  protein  of  the  tissues.  This  is  proved 
by  the  fact  that  the  total  excretion  of  nitrogen  is  increased,  at  least, 
in  proportion  to  the  amount  of  protein  ingested,  and  reaches  its  highest 
value  directly  after  the  crisis  and  during  the  period  of  defervescence. 
It  appears,  therefore,  that  the  products  of  the  bacteria  give  rise  to 
some  derangement  of  the  protoplasm  of  the  cells,  in  consequence  of 
which  the}'  are  rendered  especially  vulnerable  to  the  hydrolyzing  and 
oxidizing  agents  which  are  always  present  in  the  tissues.  The  constant 
drain  upon  the  store  of  the  tissue-proteins  then  ensuing,  cannot  be 
made  good  by  a  corresponding  intake  nor  are  the  cells  able  to  protect 
their  proteins  sufficiently  by  means  of  carbohydrates  and  fats.  Conse- 
quently, this  tearing  down  process  must  continue  and  give  rise  eventu- 
ally to  an  excessive  production  of  heat  which  is  not  compensated  for 
by  an  equally  intense  dissipation.  In  other  words,  fever  is  the  result 
and  not  the  cause  of  this  disorder  in  the  metabolism  of  the  tissues. 
The  common  view  is  that  fever  is  a  pathological  process  and  must 
be  combated,  because  the  body  cannot  long  withstand  a  temperature 
of  from  44°  to  45°  C.  But  since  fever  is  merely  one  of  the  expressions 
of  a  cellular  reaction  instituted  in  consequence  of  pathogenic  influences, 
its  removal  by  cold  baths  and  drugs  cannot  give  permanent  nor  bene- 
ficial results.  Whether  fever  as  such  possesses  a  favorable  influence 
upon  the  body  and  actually  helps  in  combating  the  pathogenic  proc- 
ess is  a  much  debated  question.  Bacteriologists,  however,  claim  that 
it  serves  as  a  protective  mechanism,  because  many  bacteria  are  killed 
at  a  temperature  slightly  above  that  of  the  bod}-.  This  is  true  of  the 
streptococcus  of  erysipelas  which  does  not  develop  at  39°  to  40°  C, 
as  well  as  of  the  bacillus  of  anthrax  which,  when  kept  at  42°  C,  is 
greatly  attenuated.  Even  the  temperature  range  of  the  bacillus  of 
diphtheria  and  of  the  pneumococcus  is  limited.  It  has  also  been  sug- 
gested that  a  high  body-temperature  may  be  required  for  a  copious 
formation  of  unmune  bodies  which  would  then  remove  the  cause  of 
the  abnormal  protein-metabolism  by  antagonizing  the  agent  of  the 
infection. 


PART  IX 
REPRODUCTION 

SECTION  XXX 
THE  REPRODUCTIVE  ORGANS 


CHAPTER  XCIII 
GROWTH,  REGENERATION  AND  REPRODUCTION 

Direct  Cell-division  or  Amitosis. — The  preceding  pages  have  been 
devoted  very  largely  to  a  discussion  of  the  processes  of  life  as  we  find 
them  in  the  adult  animal.  Looked  at  in  a  very  general  way,  these 
processes  present  themselves  as  phenomena  of  activity'  and  growth. 
Both  of  these  take  place  at  the  expense  of  the  inorganic  and  organic 
material  of  the  surrounding  medium,  and  are  the  direct  outcome  of 
stimulations.  Consequently,  life  is  not  spontaneous,  but  consists 
merely  of  responses  to  external  and  internal  impressions.  Sooner  or 
later,  however,  these  reactions  cease  and  retrogression  gains  the  upper 
hand.  Henceforth  dissimilation  continues  uninterruptedly  until  the 
complex  animal  machine  has  ceased  to  exist  as  a  Uving  entity.  Thus, 
death  is  merely  a  phenomenon  of  nature,  brought  about  by  a  serious 
derangement  of  the  processes  upon  which  life  is  based.  It  is  the 
climax  of  all  physiological  activities. 

Since  the  chief  consequence  of  death  is  the  extinction  of  the  indi- 
\4dual,  not  only  the  existence  of  a  certain  species  but  also  that  of  all 
animal  life  would  be  endangered.  In  order  to  prevent  such  an  out- 
come, nature  has  pro\'ided  a  process  of  rejuvenation  by  means  of  wliich 
new  living  entities  may  be  brought  into  existence  to  take  the  places  of 
those  used  up.  This  constitutes  the  process  of  reproduction.  Funda- 
mentally considered,  the  aspect  of  reproduction  is  the  same  as  that  of 
growth,  because  it  strives  to  accompUsh  a  multiplication  of  the  living 
substance  at  the  expense  of  the  surrounding  material.  In  the  case  of 
growth,  however,  the  new  substance  is  affixed  to  the  same  entity,  while 
in  the  case  of  reproduction,  it  is  moulded  into  an  entity  sparate  from 
the  original. 

Attention  has  previous^  been  called  to  the  fact  that  the  size  of 
anj'  given  unit  of  living  matter  is  limited,  because  it  is  held  together 

1109 


1110  THE  REPRODUCTIVE  ORGANS 

by  nothing  more  than  the  ordinary  force  of  cohesion.  Hence,  if  its 
mass  becomes  too  large,  this  force,  ampHfied  by  adhesion,  is  no  longer 
sufficient  to  act  throughout  its  substance,  in  spite  of  the  fact  that  the 
proportion  of  its  surface  to  its  mass  becomes  less  as  its  size  increases. 
Moreover,  since  the  processes  of  life  are  controlled  by  the  nuclear 
material  and  not  by  the  cytoplasm,  the  mass  of  the  latter  must  be 
restricted,  otherwise  the  nucleus  cannot  make  its  influence  felt  through- 
out the  cell.  It  is  for  this  reason  that  those  cells  which  must  of 
necessity  attain  a  large  size,  such  as  the  leukocytes  and  giant  cells, 
invariably  embrace  several  isolated  nuclei.  To  begin  with,  of  course, 
the  growth  of  these  simple  protoplasmic  units  depends  upon  the  fact 
that  their  acquisition  of  new  material  exceeds  the  destruction.  Even- 
tually', however,  when  a  limit  in  their  size  has  been  reached,  their  assimi- 
lative power  is  gradually  diminished.  Even  a  division  of  their  mass 
may  then  result,  but.  onlj^  if  it  is  also  in  possession  of  a  sufficient 
amount  of  nuclear  substance.  When  the  latter  is  removed  completely, 
the  cytoplasm  cannot  continue  to  exist  for  any  length  of  time,  because 
it  then  lacks  its  "trophic"  factor. 

Contrary  to  growth,  therefore,  the  process  of  reproduction 
depends  upon  the  formation  of  daughter-cells  by  the  division  of  the 
mother-cell;  but  it  will  be  seen  that  these  occurrences  are  not  inde- 
pendent of  one  another,  because  without  activity'  and  growth  there  can 
be  no  reproduction.  The  manner  in  which  this  rejuvenation  of  Uving 
matter  is  accompUshed  differs  greatly  in  different  animals.  The 
simplest  procedure  prevails  in  the  unicellular  organisms,  because 
these  entities  multiply  by  the  asexual  process  of  simple  division  or 
amitosis.  The  mother-cell  splits  into  two  parts,  each  of  which  is 
equipped  with  a  certain  amoimt  of  nuclear  substance.  In  accordance 
with  Remak  (1858),  cell-division  begins  wath  a  splitting  of  the  nucleolus 
which  is  then  followed  by  a  constriction  and  division  of  the  nucleus, 
cell-body  and  enveloping  membrane.  The  daughter-cell  so  formed 
grows  and  gradually  acquires  the  characteristics  of  the  mother-cell,  but 
only  if  it  is  subjected  to  identical  conditions.  If  not,  its  molecular  and 
general  morphological  character  may  be  altered  in  such  a  manner  that 
it  may  give  rise  to  an  entirely  new  species. 

This  amitotic  manner  of  reproduction  frequently  gives  rise  to  a 
perfectly  amazing  multiplication.  Thus,  it  has  been  stated  that  a 
Paramecium,  if  it  were  plentifully  supplied  with  food  and  protected 
against  injurious  influences,  would  be  able  to  form  in  the  course  of  a  year 
a  mass  of  living  matter  as  large  as  the  earth.  If  nothing  more,  this 
computation  gives  us  an  idea  regarding  the  perfectly  phenomenal  pos- 
sibihties  of  this  process.  But,  it  is  also  true  that  amitosis  cannot  con- 
tinue for  an  indefinite  period  of  time  and  certainly  not  if  the  organisms 
are  forced  to  exist  under  unfavorable  circumstances.  It  seems  that 
thej^  then  lose  their  vigor  and  become  non-resistant  so  that  they  are 
more  easily  affected  by  outside  influences.  Under  these  conditions,  a 
type  of  reproduction  is  frequently  brought  into  play  which  is  called 


GROWTH,    REGENERATION    AND    REPRODUCTION        .     1111 

conjugation  and  which  undoubtedly  is  a  prototype  of  the  interaction 
of  the  germ-cells  of  the  multicellular  forms.  Conjugation  is  essen- 
tially a  union  of  the  nuclei  of  the  conjugating  cells,  although  in  unicellu- 
lar plants  the  cell-hodies  are  fused  as  well,  while  in  the  infusoria  this 
union  is  only  temporary.  Maupas^  l)elieves  that  this  process  invari- 
ably follows  a  long  period  of  multiplication  by  cell-division  and  may 
be  compared  to  the  attainment  of  sexual  maturity  of  the  higher 
animals.  According  to  Biitschli,  its  purpose  is  to  prevent  senile 
retrogressive  changes  and  to  instil  new  vigor  into  the  descendents. 
In  the  infusoria,  Wilson^  recognizes  the  following  changes:  To 
begin  with,  each  cell  possesses  two  kinds  of  nuclei,  namely,  a  large 
macronucleus  and  one  or  several  micronuclei.  As  soon  as  the  cells 
have  become  applied,  the  former  degenerates  and  disappears.  In 
consummating  this  process,  the  micronuclcus  divides  twice  to  form  four 
spindle-shaped  bodies.  While  three  of  these  degenerate,  the  fourth 
splits  into  smaller  masses.  These  micronuclei  are  then  exchanged, 
one  from  A  passing  into  B  and  one  from  B  into  A .  Very  soon  after 
these  cells  have  again  separated  each  pair  of  nuclear  masses  unite  into 
one.  This  single  micronucleus  then  divides  three  times  to  form  eight; 
while  the  cell  meanwhile  splits  into  four  parts,  two  nuclei  being 
apportioned  to  each  daughter-cell.  One  of  the  latter  enlarges  to  form 
the  macronucleus,  while  the  other  continues  as  the  micronucleus. 

Indirect  Cell-division  or  Mitosis. — By  far  the  greatest  number  of 
animal  and  vegetable  cells  multiply  by  the  process  of  mitosis  or 
karyokinesis,  which  differs  from  amitosis  chiefly  in  the  fact  that  the 
nucleus  undergoes  a  number  of  very  characteristic  changes.  In  order 
to  be  able  to  follow  these  more  conveniently,  they  may  be  divided  into 
the  following  phases: 

(a)  Prophases,  during  which  the  division  is  initiated. 

(6)   Metaphase,  during  which  the  nucleus  undergoes  its  most  important  change. 

(c)  Anaphases,  during  which  the  nuclear  material  is  arranged  in  a  peculiar 
manner,  preparatory  to  the 

(d)  Telophases,  during  which  the  active  cell  divides,  giving  rise  to  the  daughter- 
cells. 

During  the  prophase  the  chrojnatine  substance  of  the  nucleus  acquires  a  greater 
power  of  staining,  loses  its  net-like  character  and  is  eventually  resolved  into  a 
definite  number  of  separate  bodies  possessing  intense  staining  qualities.  These 
so-called  chromosomes  are  generally  rod-shaped,  straight  or  curved,  but  may  also 
be  spherical,  ovoidal  or  ring-like.  They  arise  in  consequence  of  the  transverse 
division  of  the  spireme-thread  into  which  the  nuclear  substance  first  resolves  it- 
self. In  the  place  previously  occupied  by  the  nucleus,  the  cytoplasm  assumes  a 
radiate  appearance,  giving  rise  to  a  star  or  aster.  In  the  center  of  each  aster  lies 
a  centrosome,  while  in  between  them  is  a  spindle  of  fine  fibers,  known  as  the 
achromatic  spindle.  The  chromosomes  arrange  themselves  in  a  plane  at  the 
equator  of  the  spindle. 

The  metaphase  is  characterized  by  a  lengthwise  splitting  of  the  chromosomes 
into  equal  halves,  thus  initiating  the  actual  division  of  the  cell.  During  the  ana- 
phase these  daughter-chromosomes  move  toward  the  opposite  poles  of  the  spindle 

1  Arch,  de  Zoologie,  Sec.  II,  vn,  1889. 

-  The  Cell  in  Development  and  Inheritance,  Macmillan,  1919. 


1112 


THE    REPRODUCTIVE    ORGANS 


and  collect  here  in  groups,  finally  evoking  the  formation  of  a  daughter-nucleus. 
As  they  diverge,  the  zone  between  them  shows  a  bundle  of  achromatic  connecting 
fibers  which  are  not  identical  with  the  fibers  of  the  original  spindle.     Later  on  in 


c 


ID 


Fig.  5.30. — The  Proph.\ses  of  Mitosis  (Heterottpical  Form)  ln  PRnLVRT  SpERiiAxo- 

CTTES    OF    SaLAM.^NDRJ  . 

A,  Early  segmented  spireme;  two  centrosomes  outside  the  nucleus  in  the  remains  of 
the  attraction-sphere.  B,  longitudinal  splitting  of  the  spireme,  appearance  of  the 
astral  rays,  disintegration  of  the  sphere.  C,  early  amphiaster  and  central  spipdle. 
T>,  chromosomes  in  the  form  of  rings,  nuclear  membrane  disappeared,  amphiaster  en- 
larging, mantle-£bers  developing.      (Aferes.) 

the  course  of  the  anaphase  and  during  the  telophase,  the  entire  cell  splits  into  two 
portions,  each  of  the  daughter-cells  receiving  a  group  of  chromosomes,  half  of  the 
spindle  and  connecting  fibers  and  an  aster  with  its  centrosome.  Meanwhile,  the 
nucleus  of  the  daughter-cell  has  been  reconstructed. 


GROWTH,  REGENERATION  AND  REPRODUCTION 


1113 


It  has  hvxm  shown  that  the  number  of  chromatic  loops  differs 
greatly  in  ditferent  animals  but  is  constant  in  the  same  species.  Man 
has  sixteen  chromosomes  in  the  nucleus  of  his  somatic  cells,  while  the 
mouse  and  salamander  have  twenty-four,  those  of  Ascaris  two  or 
four,  and  those  of  the  crustacean  Artemia  one  hundred  and  sixty- 
eight.     It  appears,  therefore,  that  mitosis  effects  a  meristic  division  of 


Fig.  531. — Metaphasb  and  Anaphases  of  Mitosis  in  Cells  (Spermatocytes)  of  the 

Salamander. 

E,  Metaphase.  The  continuous  central  .spindle-fibers  pass  from  pole  to  pole  of  the 
spindle.  Outside  them  the  thin  layer  of  contractile  mantle-fibers  attached  to  the  di- 
vided chromo.somes  of  which  only  two  are  shown.  Centrosomes  and  asters.-  F,  Trans- 
verse section  through  the  mitotic  figure  showing  the  ring  of  chromosomes  surrounding 
the  central  spindle,  the  cut  fibers  of  the  latter  appearing  as  dots.  G,  Anaphase;  diver- 
gence of  the  daughter-chromosomes,  exposing  the  central  spindle  as  the  interzonal 
fibers;  contractile  fibers  (principal  cones  of  Van  Beneden)  clearly  shown.  H,  Later 
anaphase  (dyaster  of  Flemming) ;  the  central  spindle  fully  exposed  to  view;  mantle-fibers 
attached  to  the  chromosomes.     Immediately  alterward  the  cell  divides.      (Driiner.) 


the  chromatin  of  the  mother-cell,  so  that  the  daughter-cells  may  be 
equally  provided  with  this  material.  Amitosis,  on  the  other  hand, 
presents  itself  rather  as  a  division  of  mass. 

Regeneration. — Besides  growth,  an  organism  has  two  duties  to 
perform,  namely,  to  reproduce  the  cells  which  have  been  used  up  in 
its  processes  of  life,  and  secondly,  to  reproduce  its  like  in  the  form  of 


1114  THE  REPRODUCTIVE  ORGANS 

a  new  living  entity.  The  former  process  or  regeneration  may  be 
participated  in  by  practically  any  one  of  the  constituents  of  its  several 
tissues,  while  the  latter  or  reproduction,  is  effected  by  a  special  group 
of  cells.  In  fact,  the  propagation  of  the  species  is  so  important  a 
function  that  it  is  generally  mediated  by  a  set  of  specialized  cells  con- 
stituting the  organs  of  reproduction.  Thus,  the  cells  of  a  multicellular 
organism  really  arrange  themselves  into  two  groups,  namely,  into  those 
mediating  its  ordinary  processes  of  life  and  those  concerned  with  the 
generation  of  a  new  organism.  Weissman  applies  to  the  former  the 
term  of  somatic  cells,  and  to  the  latter,  the  term  of  germ-cells.  As  far 
as  the  actual  life  of  the  animal  is  concerned,  these  reproductive 
units  are  of  relatively  slight  importance  and  are  brought  into  play 
only  when  new  entities  are  to  be  formed.  But  since  even  somatic 
cells  are  able  to  reproduce  their  like,  this  distinction  is  not  absolute, 
but  merely  serves  to  indicate  a  physiological  division  of  labor  of  the 
cells  of  the  metazoan. 

The  life  of  the  organism  as  a  whole  is  limited  and  so  is  that  of  the 
numberless  constituents  of  its  different  tissues.  Cells  are  constantly 
being  destroyed,  more  so  in  some  tissues  than  in  others,  and  their  places 
are  taken  by  new^  units.  This  implies  that  even  the  ordinary  tissue- 
cells  must  possess  the  power  of  reproducing  their  like.  Thus,  we  have 
previously  noted  that  the  red  blood  corpuscles  disintegrate  while  they 
traverse  the  circulatory  system,  and  are  constantly  being  replaced  by 
new  cells  derived  from  the  red  marrow  of  the  bones.  A  similar  regener- 
ation takes  place  in  the  outermost  layer  of  the  skin  where  the  squa- 
mous epithelium  is  worn  away  and  is  restored  by  newly  formed  cells 
of  the  deeper  Malpighian  layer.  When  exercised,  the  skeletal  muscle 
acquires  new  cells,  and  so  does  the  uterus  after  its  reception  of  the 
impregnated  ovum.  The  periosteal  cells  proliferate  when  the  adjoin- 
ing bone  is  broken  (callus),  giving  rise  to  numberless  bone-corpuscles, 
many  of  which  are  again  absorbed  later  on.  Under  ordinary  circum- 
stances, however,  some  of  the  adult  tissue-cells  are  quite  unable  to 
reproduce  their  like,  which  implies  that  other  cells  must  step  in  to 
consummate  this  process.  Thus,  a  wound  in  a  muscle  is  usually  closed 
by  a  proliferation  of  its  connective  tissue  elements  and  not  by  a  mul- 
tiplication of  its  muscle  cells.  This  gives  rise  to  the  formation  of 
scar-tissue.  Furthermore,  these  processes  of  regeneration  are  in- 
variably retarded  after  middle  life  and  may  in  fact  be  abolished 
altogether.  As  an  instance  of  this  abolition  might  be  mentioned  the 
abortive  proliferation  of  the  cells  of  the  periosteum,  causing  a  per- 
manent separation  of  the  ends  of  the  fractured  bone. 

In  general,  it  may  be  said  that  the  more  highly  organized  tissues 
are  regenerated  with  greater  difficulty  than  those  of  a  more  elementary 
kind.  This  is  especially  true  of  the  master  tissue  of  our  body,  at 
least  insofar  as  the  cell-bodies  of  the  different  neurons  are  concerned, 
because  defects  of  the  central  gray  matter  are  always  repaired  with 


GROWTH,    REGENERATION    AND    REPRODUCTION  1115 

extreme  tardiness.  Harrison,'  however,  has  proved  that  nerve  cells 
may  also  be  grown  outside  the  body  in  suitable  culture  media.  When 
clotted  lymph  is  used,  the  cell-body  grows  and  sends  out  its  oxone  and 
dendrites  which  may  be  traced  far  into  the  surrounding  medium. 
This  observation  also  proves  that  nerve  fibers  are  tlu;  outgrtnvths  of 
the  hyaline  protoplasm  of  the  nerve  cells  which  at  this  stage  of  develop- 
ment is  actively  ameboid.  These  long  drawn  out  pseudopodia 
eventually  become  the  organized  fiber  processes.  Consequently, 
the  central  complexes  of  gangli(jn  cells  must  exert  a  commanding 
influence  upon  the  development  of  the  fiber  paths.  This  view  finds 
substantiation  in  the  fact  that  the  transplanted  limbs  of  the  embryos 
of  the  toad  and  frog  eventually  acquire  a  normallj'  arranged  system  of 
nerves, 2  No  matter  where  the  new  limb  is  united  with  the  body, 
these  nerves  show  a  perfectly  normal  distribution  in  relation  to  those 
of  the  host.  Thus,  a  limb  implanted  in  the  region  of  the  head,  in- 
variably acquires  nervous  outgrowths  which  are  derived  in  regular 
order  from  the  facial  nerve  or  some  other  nerve,  if  closer  to  the  graft. 
In  this  category  also  belong  the  morphological  and  embryological 
experiments  of  Pfliiger,  Roux,  Born,  and  others,  purposing  to  test  the 
regenerative  powers  of  animals  when  injured  during  their  period  of 
development  or  when  the  organic  constituents  of  the  egg  itseK  are 
either  removed  or  transplanted  from  one  animal  to  another.  One 
of  the  most  interesting  discoveries  was  made  by  Born^  in  1894.  While 
performing  certain  experiments  pertaining  to  the  reformation  of  lost 
parts  of  the  embryo  of  the  frog,  he  found  that  pieces  w^hich  had  first 
been  absolutely  separated  from  the  main  mass,  might  again  be  made  to 
unite  with  it  by  simply  holding  them  against  it  for  a  few  hours.  This 
preliminary  fact  having  been  established,  he  then  succeeded  in  uniting 
these  pieces  in  all  possible  ways,  producing  even  monsters  with  two 
tails  or  two  heads  or  a  head  in  the  place  where  the  tail  ought  to  be. 
Even  pieces  from  different  animals  could  be  used  in  the  production 
of  these  odd  forms.  With  the  help  of  the  Zeiss  binocular  dissecting 
microscope  and  delicate  instruments,  Spemann"*  was  able  to  perform 
transplantations  of  much  greater  delicacy  than  those  just  related. 
These  included  the  removal  of  certain  areas  of  the  epidermis  or  of  the 
Gasserian  ganglion  and  their  implantation  in  some  other  part  of  the 
body;  the  removal  and  reversal  of  the  auditory  vesicle,  as  well  as  the 
interchange  of  the  right  and  left  ears.  By  the  same  means  Lewds° 
proved  later  on  that  the  epidermis  of  any  part  of  the  body  may  be 
brought  into  contact  with  the  optic  vesicle  at  the  proper  stage  of 
development  and  give  rise  to  a  crystalline  lens, 

1  Proc.  Soc.  for  Esp.  Biolog.  and  Med.,  1907. 

2  Held,  Verhandl.  der  anat.  Gesellsch.,  Rostock,   1906,  and  Harrison,  Jour, 
of  Exp.  Zoology,  iv,  1907. 

^Arehiv  fiir  Entwickelungsmechanik,  iv,  1896-1897;  also  Brans,  Propfung  bei 
Tieren,  Verhandl.  des  naturhist.  med.  Vereins,  Heidelberg,  iii. 
*  Verhandl.  der  deutsch.  zoolog.  Gesellsch.,  1906. 
5  Am.  Jour,  of  Anat.,  iii,  1904,  and  Jour,  of  Exp.   Zoolog.,  ii,  1905. 


1116  •  THE    REPRODUCTIVE    ORGANS 

This  list  of  regenerative  possibilities,  however,  need  not  remain 
confined  to  the  developing  animal,  but  may  also  be  extended  to  adult 
forms,  because  while  the  growth  of  the  latter  is  greatl}-  diminished, 
their  power  of  reforming  injured  tissues  is  by  no  means  lost.  It  is 
true,  however,  that  their  property  of  regeneration  is  rather  dormant 
at  this  time,  in  consequence  of  certain  inhibitor}^  influences,  but  may 
be  awakened  temporaril}^  b}'  stimulation.  Thus,  it  is  a  well-known 
fact  that  the  adult  starfish  is  capable  of  reforming  a  lost  arm,  and  that 
a  worm  cut  into  is  able  to  develop  from  the  posterior  extremity  of  its 
anterior  segment  a  new  tail,  and  from  the  anterior  end  of  its  posterior 
segment  a  new  head.^  In  fact,  even  the  severed  arm  of  the  starfish 
may  eventuallj-  give  rise  to  a  complete  animal,  while  artificial  mouths 
surrounded  by  tentacles  may  be  produced  in  sea-anemones  by  simply 
incising  their  body-wall  and  keeping  the  wound  open.  Of  even  greater 
interest  are  those  experiments  which  show  that  parts  of  different 
animals  may  be  united  to  form  a  single  new  one.^  In  this  wa}',  com- 
pound worms  have  been  formed  which  lived  for  many  months,  and 
Harrison  has  even  succeeded  in  uniting  the  anterior  haK  of  Rana 
virescens  with,  the  posterior  half  of  Rana  palustris  (parabiosis). 
Although  both  parts  retained  their  special  characteristics,  this  com- 
pound frog  gave  rise  to  young.  Most  remarkable  changes  may  also  be 
effected  in  plants.  Thus,  it  is  a  well-known  fact  that  a  whole  plant 
may  be  produced  from  the  cuttings  of  its  branches  and  roots,  and  even 
from  its  leaves.  In  this  categorj^  also  belong  the  transplantations 
practised  to  enrich  the  flower  and  fruit  bearing  qualities  of  certain 
plants  and  trees.  With  regard  to  the  growth  of  malignant  tumors, 
it  might  be  mentioned  that  connective  tissues  may  readily  be  grown 
outside  the  body  and  that  this  growth  may  be  greatl}"  accelerated  by 
extracts  of  tissues,  particularly  of  embryos,  spleen  and  malignant 
tumors.^  Tissues  may  also  be  kept  at  a  low  temperature  without  ap- 
parently losing  their  power  of  regeneration.  Thus,  skin  may  be  kept 
for  2  to  6  weeks  in  cold  storage  and  be  grafted  successfully  at  the  end 
of  this  period. 

Reproduction. — These  examples,  no  doubt,  suffice  to  show  that 
regeneration  is  really  a  form  of  reproduction;  but  a  reproduction  of  a 
local  or  restricted  kind  which  does  not  pass  beyond  the  reformation 
of  the  individual  tissues.  Thus,  while  a  newt  may  reproduce  an 
amputated  toe,  the  newt  itself  is  left  in  its  original  condition.  Its 
cells  are  gradually  used  up  until  its  existence  as  a  living  entitj^  ceases 
altogether.     But  this  natural  hmitation  of  life  is    prevented    from 

1  Joest,  Transplantationsvers.  an  Regenwurmern,  Ber.  Gesellsch.  der  Naturw., 
Marburg,  1895;  also  Morgan,  the  Phj'siologj' of  Regeneration,  Jour.  Exp.  Zoology, 
iii,  1906,  or  "Experimental  Zoology,"  New  York,  1907. 

-  The  earliest  experiments  in  grafting  were  performed  upon  hydra  by  Trembley 
(Mem.  pour  servir  a  I'histoire  d'un  genre  de  polypes  d'eau  douce,  Leide,  1774). 
Later  on  Hunter  and  Durhamel  grafted  the  spur  of  a  cock  to  the  comb  where  it 
continued  to  grow. 

3  Carrel,  Jour.  Exp.  Med.,  xiv,  1911,  571,  and  xvi,  1912,  165. 


GROWTH,    REGENERATION    AND    REPRODIT'TION  1117 

terminating  the  existence  of  the  species  by  a  process  of  regeneration 
or  reproduction  in  mass.  A  special  group  of  organs  is  set  aside  for 
the  formation  of  what  might  be  termed  in  brief  the  germ-plasm,  a 
specialized  substance  which  is  capable  not  only  of  reforming  a  par- 
ticular type  of  cell  l)ut  also  of  repnxhicing  the  counterparts  of  all 
cells  within  a  single  entity  which  then  takes  the  place  of  the  one  gone 
out  of  existence.  The  organs  to  which  this  function  is  assigned  are  the 
reproductive  organs.  Their  chief  product  is  the  ovum,  a  cellular 
unit  containing  the  germ-plasm.  In  this  germinal  cell  begins  the 
development  of  every  new  living  entity. 

In  the  majority  of  living  forms,  however,  the  ovum  is  not  capable 
of  undergoing  division  unless  it  is  energized  by  another  cell  which  is 
known  as  the  sperm-cell  or  spermatozoon.  Thus,  reproduction  may 
be  either  asexual  or  sexual.  The  former  process  or  parthenogenesis 
is  confined  to  some  of  the  lower  and  simpler  types  of  life,  while  the 
latter  is  peculiar  of  all  higher  forms.  In  sexual  reproduction  the  ovum 
represents  the  female  element,  and  the  spermatozoon  the  male  element. 
The  former  consists  essentially  of  cytoplasm  which  contains  a  consider- 
able quantity  of  nutritive  material,  while  the  latter  is  principally 
composed  of  nuclear  substance.  The  essence  of  this  mechanism  is 
the  meeting  and  fusion  of  these  two  elements  into  a  single  one  from 
which  a  new  individual  is  then  developed.  This  fusion  by  means 
of  which  two  independent  units  are  blended  into  one,  constitutes 
the  process  oi  fertilization  or  fecundation. 

In  explanation  of  this  interaction  two  theories  have  been  promulgated,  namely, 
one  emphasizing  the  importance  of  the  spermatozoon  and  one  emphasizing  that 
of  the  ovum.  The  advocates  of  the  former  are  known  as  animalcvlists  and  hold 
that  the  spermatozoon  is  a  complete  animal  en  minuture,  possessing  all  the  char- 
acteristics of  the  parent  but  lacking  a  fertile  medium  in  which  to  grow.  This 
medium  it  seeks  and  finally  attains  by  virtue  of  its  inherent  power  of  movement. 
The  advocates  of  the  second  view,  Tvho  are  known  as  oHsts,  believe  that  the  ovum 
contains  all  the  essentials  of  the  full  grown  organism,  but  needs  a  stimulus  to  make 
it  develop.  This  impetus  is  given  to  it  by  the  spermatozoon.  In  accordance  with 
this  view  the  ovum  may  be  likened  to  the  bud  of  a  plant  which  unfolds  its  leaflets  and 
begins  to  grow  as  soon  as  the  proper  stimuli  have  been  received  by  it.  Both  these 
conceptions  are  based  upon  the  idea  that  either  the  spermatozoon  or  the  ovum  are 
preformed  and  hence,  they  may  be  collectively  referred  to  as  the  theory  of  preforma- 
tion. Subsequent  investigation,  however,  has  shown  that  the  spermatozoon  as 
well  as  the  ovum  are  but  single  cells  and  have  a  perfectly  definite  life  history. 
Both  originate  in  the  germinal  cells  of  two  separate  individuals,  and  both  pass 
through  definite  preliminary  changes  before  they  actually  attain  their  maturity. 
Furthermore,  while  the  part  played  by  them  in  fertilization  is  not  exactly  the  same, 
their  purpose  is  identical,  i.e.,  both  strive  to  produce  a  new  individual.  Conse- 
quently, neither  can  be  said  to  be  more  important  than  the  other. 

It  must  be  admitted,  however,  that  we  are  still  in  ignorance  regarding  the  physi- 
ological principle  underlying  this  fusion  of  the  germinal  elements.  Harvey  and 
others  have  advocated  the  view  that  the  ovum  is  animated  by  the  spermatozoon 
and  is  thereby  made  to  develop.  This  idea  is  embodied  in  the  so-called  dynamic 
theories  of  Spencer,  Biitschli,  and  Hertwig,  which  assume  that  protoplasm 
becomes  increasingly  inactive  and  finally  requires  fertilization  to  imbibe  it  with 
a  new  force  developed  under  different  conditions.  .  This  process,  therefore,  could 


1118  THE  REPRODUCTIVE  ORGANS 

be  compared  with  the  rejuvenation  effected  in  "senile"  protozoon  by  the  method 
of  conjugation.  A  somewhat  different  explanation  is  made  possible  by  the  sugges- 
tions of  Trivianus,  Brooks,  and  Weismann,  that  fertilization  is  essentially  a  process 
hy  means  ofwhicli  iHiriations  are  produced  in  consequence  of  the  acquisition  of  second- 
ary elements,  insuring  a  constant  mingling  and  repeated  renewal. 

The  Fertilization  of  the  Ovum. — The  physiological  principle 
underlying  sexual  reproduction,  is  the  process  of  fertilization  effected 
by  the  fusion  of  the  two  germ-cells,  one  of  which  is  of  maternal  and 
the  other  of  paternal  origin.  In  most  cases,  this  union  takes  place 
within  the  body  of  the  mother,  but  may  also  be  accomplished  in  an 
outside  medium  which  is  accessible  to  both  the  female  and  male  germ- 
cells.  The  manner  in  which  these  elements  are  brought  together 
differs  greatly  in  different  animals,  and  hence,  the  subsequent  discus- 
sion pertaining  to  the  mechanics  of  sexual  reproduction,  must  nec- 
essarily be  restricted  to  an  enumeration  of  the  functions  of  the 
different  sexual  organs  of  the  mammals.  The  minute  changes,  how- 
ever, are  usually  studied  in  the  eggs  of  the  lower  forms,  for  example, 
in  those  of  the  sea-urchin  and  the  thread-worm. 

Subsequent  to  the  discovery  of  the  spermatozoon  by  Hamm 
(1677),Leeuwenhoek  expressed  the  idea  that  this  element  must  pene- 
trate the  egg,  an  assumption  which  was  later  on  confirmed  by  Spal- 
lanzani  (1786),  Newport  (1854),  and  Pringsheim  (1855).  It  seems, 
however,  that  only  the  head  of  the  spermatozoon  actually  takes  part 
in  the  fertilization,  because  in  some  animals,  such  as  the  echinoderms, 
the  tail  remains  entirely  outside  the  egg.  But  it  is  also  true  that 
the  eggs  of  the  molluscs,  insects,  nematodes  and  some  annelids  fre- 
quently display  the  tail  of  the  spermatozoon  within  their  cytoplasm, 
forming  here  a  delicate  coiled  up  structure.  At  the  time  of  contact 
between  the  male  and  female  elements,  the  ovum  produces  two  minute 
globular  masses  at  its  upper  extremity  which  are  known  as  the  polar 
bodies.  Since  these  projections  take  no  part  in  the  subsequent  changes 
but  degenerate  and  may  make  their  appearance  even  before  the  en- 
trance of  the  spermatozoon,  it  seems  that  they  merely  indicate  that 
the  egg  has  reached  its  mature  state  and  is  ready  to  receive  the  male 
sperm-cell.  In  all  probability,  a  place  of  least  resistance  is  formed  by 
this  means,  through  which  the  spermatozoon  first  arriving  in  this 
vicinity,  is  enabled  to  enter.  Immediately  upon  conception,  a  tough 
envelope,  the  vitalline  membrane,  is  developed  around  the  ovum, 
thereby  preventing  the  entrance  of  those  spermatozoa  which  may  have 
reached  their  destination  during  the  interim.  As  soon  as  the  head  of 
the  successful  spermatozoon  has  been  lodged  in  the  cytoplasm,  the 
tail  atrophies  and  disappears.  Now  follows  a  gradual  enlargement  of 
the  former  and  the  breaking  up  of  its  chromatin  material  into  a  thread- 
like formation  and  its  characteristic  number  of  chromosomes.  The 
egg  then  embraces  two  nuclei  (Hertwig,  1875),  one  of  which  is  of  pater- 
nal and  the  other  of  maternal  origin.  This  is  the  crucial  point  of 
fertilization,   because  these  male   and   female   pronuclei,   containing 


Outer  cells 


Outer 

tet/s 


Fig.  532. — 1,  2,  3.  Diagrams  Illustrating  the  Segmentation  of  the  Mammalian 
Ovum  (Allen  Thomson,  after  van  Beneden).  4.  Diagram  Illustrating  the  Rela- 
tion OF  the  Primary  Layers  of  the  BijAstoderm,  the  Segmentation-cavity  of  this 
Stage  Corresponding  with  the  Archenteron  of  Amphioxus  (Bonnet). 


GROWTH,    REGENERATION    AND    REPRODUCTION  1119 

equal  amounts  of  cliroinatin  of  dual  origin,  now  approach  one  another 
and  are  joined  or  ev(!n  fuse  into  one  which  is  known  as  the  cleavage 
or  scguientation-nuclcus.  Shoi'tly  afterward  tlie  nuclear  meml)ranc 
disappears,  a  si)indle  is  developed  and  a  number  of  chromosomes 
arise  from  the  cleavage-nucleus  which  in  all  probability  have  been 
derived  in  equal  proportions  from  the  two  germ-nuclei.  Fertilization 
is  then  rapidly  followed  by  the  division  of  the  cell,  the  stimulus  for 
it  having  been  given  by  the  centrosome  which  thus  becomes  the 
controlhng  agent  in  the  further  development  of  the  embryo. 

The  successive  divisions  now  following  eventually  give  rise  to  numerous  cells 
which  arrange  themselves  in  the  form  of  either  a  spherical  mass  (morula)  or  a 
circular  disc.  In  the  former  case,  the  center  finally  becomes  hollow,  forming  the 
blastula.  These  cells  then  arrange  themselves  as  a  uniform  layer  which  is  known 
as  the  blastoderm.  Somewhat  later  the  blastula  is  invaginated  (gastrula),  thereby 
giving  rise  to  two  layers  of  cells,  namely,  an  outer  or  ectoderm,  and  an  inner  or 
entoderm.  The  next  step  in  this  development  is  the  formation  of  a  third  or 
median  layer  which  is  known  as  the  mesoderm.  In  this  way,  the  foundation  is 
laid  for  a  physiological  division  of  labor,  because  from  these  three  layers  are  de- 
rived the  various  organs  of  the  adult  individual.  But  the  question  of  whether 
this  mesoderm  arises  from  the  entoderm  or  from  the  ectoderm,  has  not  been  defi- 
nitely settled  as  yet;  in  fact,  it  seems  that  it  may  originate  from  either.  This 
differentiation  of  the  germinal  layers  having  been  completed,  genesis  begins.  The 
ectoderm  or  epililast  eventually  gives  rise  to  the  central  nervous  system  and  the 
epidermal  tissues,  while  the  mesoderm  or  mesolslast  originates  the  vascular,  mus- 
cular and  bony  tissues  as  well  as  the  generative  and  excretory  organs,  exclusive 
of  the  bladder,  the  first  part  of  the  male  urethra  and  the  female  urethra.  The 
entoderm  or  hypoblast  forms  the  epithelium  of  the  intestines  as  well  as  that  of  the 
intestinal  glands  and  respiratory  passage,  the  prostatic  portion  of  the  male  urethra 
and  the  entire  female  urethra.  ^ 

Parthenogenesis  and  Artificial  Parthenogenesis. — Sexual  repro- 
duction necessitates  the  conjugation  of  two  cells  and  the  fusion  of 
their  nuclei.  During  this  process  the  number  of  the  chromosomes  in 
the  germ-cells  is  reduced  to  one-half  the  number  characteristic  of  the 
somatic  cells. ^  In  a  few  instances,  however,  the  ovum  alone  is  capable 
of  producing  a  new  individual;  but  this  mode  of  reproduction,  which  is 
known  as  parthenogenesis,  remains  confined  to  the  simplest  forms, 
such  as  the  insects  and  the  lower  crustaceans  and  rotifers.  It  should 
also  be  noted  that  in  some  species  parthenogenesis  alternates  with 
sexual  generation,  but  the  variability  of  the  non-sexual  offsprings  is  as 
great  as  that  of  the  sexual  ones.  This  fact  speaks  against  the  concep- 
tion of  Weissman,  according  to  which  the  purpose  of  sexual  reproduc- 
tion is  to  induce  variations. 

In  parthenogenesis  the  stimulus  is  given  by  the  second  polar  body 
which  thus  takes  the  place  of  the  spermatozoon.     The  ovum  develops 

1  For  a  more  detailed  discussion  of  the  process  of  fertilization  the  reader  is 
referred  to  textbooks  on  Embryology,  and  especially  to  such  books  as  Wilson's 
"The  Cell  in  Development  and  Inheritance."  This  brief  account  has  been 
inserted  here  merely  to  serve  as  a  connecting  link  between  the  substance  of  this 
chapter  and  that  of  the  succeeding. 

-  Van  Beneden,  Arch,  de  Biologic,  iv,  1883. 


1120  THE  REPRODUCTIVE  ORGANS 

with  the  chromosomes  of  the  female  pronucleus,  i.e.,  with  one-half  the 
number  allotted  to  it  in  sexual  reproduction.  A  similar  result  is  ob- 
tained during  the  development  of  denucleated  portions  of  mature  ova 
when  fertilized  by  spermatozoa.  Since  the  nucleus  is  the  essential 
factor,  the  development  occurs  in  the  former  case  without  admixture 
with  the  male  element  and,  in  the  latter,  without  the  properties  of  the 
female. 

Parthenogenesis  may  also  be  incited  artificially.  Shortly  after 
Bataillon  succeeded  by  means  of  mechanical  impacts  in  causing  unfer- 
tilized eggs  to  develop,  J.  Loeb^  showed  that  the  fertilized  egg  of  the 
sea-urchin  may  be  prevented  from  developing  by  abstracting  the  oxy- 
gen from  the  sea-water  by  means  of  KCN  or  NaCN.  In  1899,  this 
author  found  that  the  unfertilized  eggs  of  the  same  species  may  be 
made  to  develop  into  larva?  by  exposing  them  during  a  period  of  two 
hours  to  hypertonic  salt  solutions. ^  By  altering  the  medium  by  the 
addition  of  formic  or  lactic  acid  he  finally  succeeded  in  causing  the 
unfertilized  ova  of  this  and  other  species  to  develop  their  membrane 
as  well  as  those  initial  changes  which  normally  require  the  entrance  of  the 
spermatozoon.  After  their  exposure  to  the  aforesaid  acids,  the  eggs  were 
transferred  into  concentrated  sea-water  and  subsequently  into  ordinary 
sea-water,  Loeb  suggests  that  the  action  of  the  spermatozoon  is 
chemical  in  its  nature,  because  it  brings  a  certain  substance  into  the 
ovum  which  is  capable  of  inciting  therein  a  definite  chemico-physical 
reaction.  The  nature  of  this  substance  is  still  unknown,  although 
repeated  attempts  have  been  made  to  isolate  it.  The  eggs  of  the  sea- 
urchin,  however,  have  yielded  upon  extraction  with  a  hypotonic  salt 
solution  and  ether  a  substance  which  possesses  strong  fertilizing, 
agglutinating  and  cytolytic  properties.  Furthermore,  a  chemical 
substance  has  been  isolated  from  the  head  of  the  Rhine  salmon  which 
consists  of  nucleic  acid  and  a  protamin.  It  is  known  as  salmin. 
Similar  substances  are  the  clupein  of  the  spermatozoa  of  the  herring, 
and  sturin  from  those  of  the  sturgeon.^ 

The  Law  of  Mendel. — The  general  conception  is  that  the  perplex- 
ing multiformity  among  animals  and  plants  is  due  to  the  propagation 
of  established  forms  by  heredity,  and  that  new  types  find  their  origin 
in  variation.  Darwin's  ''Origin  of  the  Species"  is  the  first  attempt  to 
analyze  these  phenomena  in  a  rational  way  and  to  refer  them  to  natural 
selection,  in  accordance  with  the  practice  of  breeders  and  experimental 
botanists  to  fix  characteristics  and  to  produce  new  ones  by  interbreed- 
ing and  grafting.  In  this  case,  heredity  may  be  amplified  by  the  adap- 
tation of  the  individual  to  dominating  conditions,  as  is  clearly  depicted 
by  the  struggle  for  existence  "and  the  consequent  survival  of  the 
fittest. "  Herbert  Spencer,  in  particular,  has  made  use  of  this  hypoth- 
esis in  explaining  many  structural  and  functional  characteristics  of 

1  Pfliiger's  Archiv,  Ixii,  895,  249. 

^  Untersuchungen  iiber  ktinstl.  Parthenogenese,  Leipzig,  1906. 

3  Burian,  Ergebn.  der  Physiol.,  i,  1904. 


GROWTH,    REGENERATION    AND    REPRODUCTION  1121 

animals  and  plants.  ]\Ioroovor,  stimulated  by  the  close  similarity 
between  the  clianges  ]M'es(>nted  by  the  developing  ova  of  widely  dii'fer- 
ent  species,  Hiickel  foiiiiulated  his  Gastraea-theory  which  states  that 
all  forms  of  blastoderms,  consisting  of  two  germinal  layers,  may  be 
regarded  as  a  modified  simple  gastriila.  In  the  same  way  as  the  gas- 
trula  is  the  beginning  of  the  formation  of  a  single  individual,  so  may 
an  animal  of  similar  simple  construction  be  considered  as  the  ancestor 
of  all  multicellular  forms.  While  this  view  has  been  widely  dissemi- 
nated, it  lacks  confirmation,  because  it  has  not  been  proved  that  a 
gastrula  gives  rise  to  any  other  entity  than  that  from  which  it  has 
arisen.  Furthermore,  the  preceding  discussion  pertaining  to  the  ferti- 
lization of  the  ovum  must  have  shown  that  the  differentiation  really 
takes  place  much  sooner,  i.e.,  at  the  time  of  fusion  of  the  pronuclei. 

The  Darwinian  theory  of  evolution  is  based  upon  slowly  developing 
anatomical  peculiarities  to  which  have  been  added  certain  data 
derived  from  artificial  selection.  Thus,  an  experimental  element  was 
introduced  for  the  first  time  which,  however,  was  again  lost  sight  of 
later  on.  Opposed  to  this  contention  is  the  theory  of  mutation  which 
is  founded  upon  phenomena  of  cell-life.^  Since  racial  characteristics 
are  no  doubt  mapped  out  in  the  segmenting  ovum,  all  homologies  or 
similarities  appearing  later  on,  must  find  their  origin  in  the  material 
substance  of  the  fertilized  egg.  Quite  similarly,  any  modification  in 
the  germinal  arrangement  must  give  rise  to  mutations  which  charac- 
terize evolution. 

In  sexual  reproduction  it  may  be  surmised  that  the  carriers  of  the 
characteristics  are  the  chromosomes,  which  thus  impart  to  the  new 
individual  the  peculiarities  of  its  parents.  This  transfer,  however, 
is  not  always  effected  in  a  proportional  measure,  but  often  favors 
more  particularly  the  male  or  female  parent.  We  have  seen  that  the 
mitosis  then  occurring,  is  associated  with  a  reduction  of  the  number  of 
chromosomes,  and  hence,  any  variation  shown  by  the  offsprings  may 
be  referred  to  the  qualitative  differences  in  the  chromosomes  which 
have  been  formed  during  the  development  of  the  ovum.  The  manner 
in  which  gross  as  well  as  minor  characteristics  may  be  transmitted  has 
been  more  fully  illustrated  by  the  results  of  an  elaborate  series  of 
experiments  performed  by  MendeP  upon  different  varieties  of  peas. 
The  bearing  of  these  experiments,  however,  has  not  been  fully  appre- 
ciated until  about  the  year  1900.  At  this  time  DeVries  found  that 
the  seeds  of  Lamark's  primrose,  sown  in  his  experimental  garden,  gave 
rise  not  only  to  a  small  percentage  of  the  same  type  but  also  to  new 
types  of  which  he  recognized  seven.  When  self-fertilized,  these  muta- 
tions not  always  bred  true  to  their  type,  but  produced  at  times  new 
varieties.     Mendel's  first  experiments  were  carried  out  upon   peas. 

1  Buff  on,  Historie  naturalle,  1755;  Lamarck,  Rech.  sur  I'orlgination  des  corps 
vivants,  1802;  St.  Hilaire,  Princ  de  philosophic  zoologique,  1830;  Weissman, 
On  germinal  selection  as  a  source  of  definite  variation,  1896,  and  DeVries,  Ernahr- 
ung  und  Zuchtwahl,  Biol.  Zentralbl.,  xx,  1900. 

2  Versuche  tiber  Pfianzenhybriden,  Briinn,  1866. 

71 


1122  THE  REPRODUCTIVE  ORGANS 

On  crossing  a  plant  of  a  tall  variety  with  one  of  a  dwarf  type,  he 
noted  that  the  seeds  obtained  from  them  gave  rise  exclusively  to  tall 
plants.  When  the  latter  were  then  recrossed  among  themselves,  the 
result  was  75  per  cent,  of  tall  and  25  per  cent,  of  dwarf  plants.  The 
subsequent  crossing  of  the  latter  with  one  another  yielded  only  dwarf 
plants  through  successive  generations.  The  former,  on  the  other  hand, 
fell  into  two  groups,  because  while  25  per  cent,  of  them  continued  to 
yield  tall  types,  the  other  50  per  cent,  gave  rise  to  75  per  cent,  of  tall  and 
25  per  cent,  of  dwarf  plants.  Mendel  explained  these  results  by  stating 
that  characters  are  either  dominant  or  recessive.  In  the  preceding  ex- 
ample, the  tallness  is  dominant  and  the  dwarf  condition  recessant. 

This  principle  maj-  be  made  clearer  at  the  hand  of  the  following  example:  If 
a  gray  (A)  and  white  (B)  mouse  are  crossed,  the  offspring  (d)  will  be  all  gray. 
If  the  gray  mice  are  now  bred  to  each  other,  the  young  (Co)  will  be  either  gray  or 
white  in  the  proportion  of  3:1.  On  crossing  the  white  of  this  generation,  only 
white  offspring  will  be  obtained  throughout.  The  graj'  individuals,  on  the  other 
hand,  will  give  rise  to  one-third  of  gray  and  two-thirds  of  white  offsprings.  On 
recrossing  the  former  only  gray  young  are  gotten,  while  the  latter  \neld  both  white 
and  gray.  From  the  white  of  this  last  generation  only  pure  white  are  obtained, 
while  the  gray  may  be  either  pure  gray  or  gray-dominant-white  recessives  A  (B). 

In  applying  Alendel's  Law  to  animals,  it  may  be  assumed  that  the 
two  kinds  of  germ-cells  are  individualized  as  dominants  and  recessants 
or  that  the  germ-cells  of  the  hybrid  are  alike,  i.e.,  that  they  contain 
both  dominant  and  recessive  characters  which  are  then  either  brought 
forth  or  suppressed  during  fertilization  in  consequence  of  certain 
external  and  internal  factors.  While  the  former  explanation  is  the 
more  simple,  it  nevertheless  fails  to  account  for  certain  phenomena, 
as  does,  in  fact,  Mendel's  Law  itself.  Thus,  the  crossing  between 
members  of  the  white  and  black  races  of  man  does  not  give  rise  to 
either  type,  but  to  an  intermediate  progeny,  showing  various  degrees 
of  admixture. 


CHAPTER  XCIV 

THE  MALE  AND  FEMALE  REPRODUCTIVE  ORGANS 

The  Testicles. — The  reproductive  organs  of  the  higher  animals 
may  be  divided  into  two  classes,  namely,  those  actually  producing  the 
generative  elements,  and  those  serving  as  a  means  of  bringing  these  two 
elements  together.  The  former  embrace  the  testes  and  ovaries,  and  the 
latter,  the  penis,  seminal  ducts,  vagina,  uterus  and  Fallopian  tubes. 
The  essential  sexual  organ  of  the  male  comprises  the  testes,  two  oblong 
glands,  each  of  which  measures  about  4  cm.  in  length,  3  cm.  in  breadth 
and  2  cm.  in  thickness  it  weighs  15  to  25  grams.  These  organs  are 
contained  in  a  sac-like  appendage,  the  scrotum,  which  is  divided  into  two 


THE  MALE  AND  FEMALE  KEPRODUCTIVE  ORGANS 


1123 


halves  by  a  median  raph6  and  incomplete  septum.  The  skin,  with  the 
underlying  daiio.s,  assumes  a  corrugated  appearance  under  the  influence 
of  cold,  this  effect  being  due  to  the  contraction  of  the  smooth  muscle 
cells  which  are  scattered  throughout  this  tissue.  The  activity  of  these 
muscle  fibers  is  greatly  influenced  by  the  general  condition  of  the 
body,  their  tonicity  and  contractility  Vjeing  much  diminished  during 
states  of  depression  and  in  old  age.  The  areolar  envelope  of  the  tes- 
ticle embraces  scattered  bundles  of  striated  muscle  which  constitute 
the  so-called  cremaster  rnuscle.  They  are  continuous  with  the  lower 
fibers  of  the  internal  oblique  muscle,  and  their  contraction  shortens 
the  funiculus  and  raises  the  testicle.  Their  action  is  controlled  by 
the  genital  branch  of  the  genito-femoral  nerve. 

In  cross-section  each  testis  is  seen  to  be  enveloped  by  a  dense  fibrous  mem- 
brane, or  tunica  alhuginea,  which  enters  its  interior  as  radial  septa  and  divides 
it   into  numerous  compartments.     These  spaces  are  occupied   by   the   secreting 


Fig.  533. — Diagrammatic  View  of  the  Seminiferous  Tubules. 
A,   Tunica   albuginea;  S,   septula;    M,  mediastinum,  and  vasa  recta;  R,  rete  testis; 
E,    vasa    efferentia;    Ep,    epididymis;    G,    globus    major;    GM,   globus   minor;   D,  vas 
deferens. 


elements,  the  seminiferous  tubules,  all  of  which  are  arranged  divergently  from  a  com- 
mon center,  formed  by  the  vasa  recta.  Each  tubule  pursues  at  first  a  very  circui- 
tous course,  but  straightens  out  as  soon  as  it  approaches  the  mediastinal  septum, 
where  it  unites  with  others  into  from  20  to  30  straight  tubes  or  vasa  recta.  The 
latter  traverse  the  mediastinum  to  form  the  rete  testis.  The  total  number  of  seminif- 
erous tubules  has  been  estimated  at  from  800  to  1000.  When  completely  unfolded, 
each  measures  from  30  to  50  cm.  in  length,  and  possesses  a  diameter  of  0.3  mm. 
Centrally  to  the  rete,  the  small  ducts  again  become  convoluted,  and  unite  to  form 
the  vasa  efferentia.  In  this  way  is  formed  the  epididyynis,  a  convoluted  single  duct 
measuring  about  7  m.  in  length  and  0.4mm.  in  diameter.  This  collecting  channel 
descends  behind  the  testicle  to  its  lower  border,  where  it  passes  over  into  the 
vas  de/ereMs,  an  ascending,  rather  straight  tube  which  traverses  the  abdominal  ring 
and,  by  following  the  under  surface  of  the  base  of  the  bladder,  eventually  termi- 
nates in  the  prostatic  division  of  the  urethra.  The  vas  deferens  is  about  60  cm.  in 
length  and  posse.sses  a  diameter  of  from  2  to  3  mm. 

This  recurrent  course  of  the  seminal  collecting  tube  finds  its  origin  in  the  fact 
that  the  testes  are  developed  in  the  peritoneal  cavity  from  the  germinal  epithe- 


1124 


THE    REPRODUCTrV'E    ORGANS 


Nucleus. 


—  End-knob. 


Middle-piece. 


Envelope  of  the  tail. 


■  Axial  filament. 


lium,  and  descend  later  on  through  the  abdominal  ring  into  the  gradually  enlarg- 
ing scrotum.  Their  descent  through  the  ring  takes  place  shortly  before  birtb. 
This  fact  also  accounts  for  the  peculiar  blood  supply  of  these  organs  which  is  de- 
rived from  the  abdominal  aorta  by  the  slender  and  unusually  long  spermatic 
arteries.  The  venous  return  is  effected  by  the  spermatic  veins,  the  right  one 
entering  the  inferior  cava  directh',  and  the  left  one,  the  left  renal  vein.  Inasmuch 
as  the  latter  joins  the  renal  almost  at  right  angles,  it  cannot  discharge  its  blood 

with  absolute  freedom,  a  condition  which  in  later 
years   often   gives   rise  to  a  venous  engorgement 
Apical  body  or  acrosome.    and  a  lower  position  of  the  corresponding  organ. 

The  Development  and  Character  of  the 
Spermatozoa. — Up  to  the  time  of  puberty, 
the  seminal  tubules  are  filled  with  cells 
containing  unusually  large  nuclei.  Among 
these  are  found  the  sjiermatogonia  which 
then  discontinue  their  divisions  and  rapidly 
develop  into  the  so-called  spermatocytes. 
From  these  arise  by  hetero-mitosis  the  sper- 
matids  or  sperm-cells,  and  from  these  in  turn 
the  adult  spermatozoa.  Each  spermatocyte, 
however,  divides  into  two  daughter-C6?lls 
and  the  latter  in  turn  into  two,  so  that 
really  four  spermatids  and  spermatozoa  are 
developed  from  each  primary  spermatocji:e. 
The  nuclear  material  of  the  spermatid  is 
transformed  directly  into  that  of  the  sper- 
matozoon, while  its  cytoplasm  is  appor- 
tioned to  the  tail.  In  some  cases,  however, 
the  centrosome  of  the  spermatid  is  con- 
verted into  the  middle  piece  and  the  axial 
filament  of  the  tail.  This  process,  there- 
fore, is  not  a  mere  division  of  the  cell,  but 
a  reduction-mitosis,  the  chromosomes  being 
reduced  by  one-half.  In  this  regard,  the 
formation  of  the  spermatozoon  is  analogous 
to  the  maturation  of  the  ovum  during  the 
projection  of  the  polar  bodies^  but  since 
the  union  of  these  two  elements  eventually 
restores  the  original  number  of  chromo- 
somes, the  spermatozoon  and  ovum  really 
supplement  one  another. 
When  fuUy  formed,  the  spermatozoa  are  forced  into  the  epididymis 
and  vas  deferens,  but  since  they  do  not  become  motile  until  they  have 
reached  the  former,  their  progress  through  the  more  distal  channel 
must  be  effected  by  the  lining  cells  of  the  seminiferous  tubules  and 
differences  in  pressure.  In  the  vas  deferens,  they  are  then  able  to 
unfold  their  power  of  movement  more  fully  and,  besides,  this  tube 
greatly  facilitates   their  progress  by  its   peristaltic   contractions   as 


End-piece. 


Fig.  5.34. — Diagraai  of  the 
Flagellate  Speril\tozoon. 
(From  Wilson,  "The  Cell  in  De- 
velopment and  Inheritance") 


THE    MALE    AND    FEMALE    KEPRODUCTHE    ORGANS 


1125 


well  us  by  the  action  of  the  cilia-like  appendages  of  some  of  its  lining 
colls. 

The  spermalozoun  is  a  coinplcti^  cell,  consisting!  of  a  nucleus  and  cytoplasm. 


In  many  cases,  however,  it  is 
opposite  sex,  the  ovum. 


times  smaller  tiian  the  germinal  cell  of  the 


100,000 
It  has  the  appearance  of  a  minute  tadpole  and  presents  a 
nucleus  which  forms  the  principal  portion  of  its  conoid  and  slightly  flattened  head, 
an  apical  piece  or  acrosome  at  the  front  of  the  head,  a  middle  pierce  directly  behind 
the  head,  and  a  long  slender  tail  or  flagellum.  Its  total  length  measures  from 
50  to  SO  ix.^  Physiologically  considered,  its  nucleus  derives  its  importance  from  the 
fact  that  it  contains  the  chromatin,  while  its 
middle  piece  represents  the  centrosonic 
element  which  serves  as  the  stimulus  to 
division.  Its  apical  piece  is  of  importance 
because  it  enables  the  spermatozoon  to  borc^ 
its  way  into  the  oviun,  and  its  tail  becausi; 
its  contractile  substance  furnishes  the  motile 
power  by  means  of  which  this  chemical 
complex  is  enabled  to  reach  the  passive 
ovum. 

The  formation  of  spermatozoa  be- 
gins at  the  time  of  puberty  or  sexual 
maturity,  i.e.,  in  temperate  climates  at 
about  the  fifteenth   year.      Some   of 


Fig.  535.  Fig.  53G. 

Fig.  535. — Diagram  to  Represent  the  Progressive  Serpentine  Movements  of 
THE  Tail  of  the  Spermatozoon. 

Fig.    536. — Diagram  of  the  Bladder,  Prostate  Gland,  Root  of  Penis,  etc. 

CI,  Part  of  base  of  bladder  covered  by  peritoneum,  separated  by  a  dotted  line  from  a 
triangular  space  left  uncovered  by  that  membrane;  V,  ureter;  S.V,  seminal  vesicle; 
ED,  ejaeulatory  duct;  P,  prostate;  M,  membranous  part  of  the  urethra;  B,  bulb;  C.S, 
corpus  cavernosum  urethrse;  C,  crus  penis;  C.G,  Cowper's  gland.     (/.  Symington.) 


the  adjunct  powers  of  the  sexual  mechanism,  however,  may  have 
been  active  for  some  years  before  this  time;  for  example,  the  erec- 
tion of  the  penis  and  sexual  desire.  Thus,  the  only  definite  sign  of 
maturity  is  the  presence  of  fully  developed  spermatozoa  in  the  semen. 
This  change  is  associated  as  a  rule  with  a  greater  stability  of  the  body 
as  a  whole.     The  voice  becomes  deeper,  owing  to  a  more  rapid  growth 

1  Eberth,  in  Bardeleben's  Handb.  der  Anatomie  des  Menschen,  Jena,   1904. 


1126  THE  REPRODUCTIVE  ORGANS 

of  the  larynx,  while  the  legs,  arms  and  other  parts  cease  their  often 
very  prolific  growth  and  increase  in  compactness  rather  than  in  length. 

The  Seminal  Vesicles.  The  Semen. — Shortly  before  its  entrance 
into  the  prostatic  urethra,  the  vas  deferens  receives  a  duct  from  the 
vesicula  seminalis,  and  is  now  known  as  the  ejaculatory  duct.  Each 
seminal  vesicle  is  about  4  cm.  in  length,  pyriform  in  shape,  and  oc- 
cupies with  its  fellow-organ  the  under  surface  of  the  bladder,  directly 
behind  the  prostate  gland.  Its  wall  consists  of  an  external  fibrous 
coat,  a  middle  muscular  coat  and  an  internal  mucous  coat.  The 
mucosa  is  beset  with  numerous  tubular  albuminous  glands  which  add 
a  stringy  constituent  to  the  semen,  consisting  chiefly  of  globulins. 
Since  the  semen  becomes  more  fluid  upon  standing,  it  seems  that  these 
globular  masses,  which  have  been  added  to  it  by  the  seminal  vesicles, 
merely  serve  the  purpose  of  giving  a  greater  volume  to  it.  In  fact,  in 
some  animals  this  material  is  made  to  clot  through  the  agency  of  a 
ferment  derived  from  the  prostate  gland.  Obviously,  this  would 
tend  to  obstruct  the  orifice  of  the  vagina  and  thus  prevent  the  loss  of 
spermatozoa.  But  it  cannot  be  said  that  the  seminal  fluid,  plus  the 
spermatozoa  and  testicular  secretion,  constitutes  the  entire  semen,  be- 
cause this  medium  receives  in  addition  the  products  of  the  prostatic 
and  urethral  glands. 

The  prostate  gland  attains  the  size  of  a  chestnut  and  consists  of  30 
to  50  lobules  with  15  to  30  ducts  which  open  near  the  orifice  of  the 
ejaculatory  duct.  The  prostatic  secretion  is  thin,  cloudy,  slightly 
alkaline,  and  contains  albumin  but  no  mucin.  The  urethral  or  Coic- 
-per's  glands  are  represented  by  two  small  globular  masses,  one  on  each 
side  of  the  prostate,  which  empty  their  product  into  the  cavernous 
portion  of  the  urethra.  Their  ducts  measure  3  to  4  cm.  in  length. 
Their  secretion  is  alkaline  and  rich  in  mucin.  Droplets  of  it  appear 
sometimes  in  the  meatus  urethrse  after  micturition  or  after  sexual 
excitement  which  has  not  actually  led  to  an  emission  of  semen. 

The  semen  is  grayish-white  in  color,  and  possesses  a  mucilaginous 
consistency.  Its  specific  gravity  varies  between  1.027  to  1.040.  Its 
very  characteristic  odor  is  derived  from  the  spermin  of  the  prostatic 
secretion.  The  amount  discharged  during  one  ejaculation  varies 
between  1  and  6  c.c.  in  accordance  with  the  ssxual  activity  of  the  indi- 
vidual, and  each  emission  may  furnish  as  many  as  22v'>,000,000  of  sper- 
matozoa.^ These  elements  are  formed  constantly  and  are  then  stored 
in  the  seminal  vesicles  and  adjoining  tortuous  portion  of  the  vas 
deferens.  The  fact  that  the  liquid  here  collected  contains  about  70,- 
000,000  of  spermatozoa  per  cubic  centimeter,  although  only  one  of 
them  is  sufiicient  to  fertilize  the  ovum,  shows  how  liberal  and  fixed 
in  its  purpose  nature  actually  is  when  the  propagation  of  the  species 
is  at  stake. 

The  Erectile  Tissues  of  the  Male. — The  transfer  of  the  semen  into 
the  seminal  receptacle  of  the  female  is  made  possible  by  the  act  of 

»  Lode,  Pfluger's  Archiv,  1,  1891,  278. 


THE    MALE    AND    FEMALE    llEPUODUCTIVE    ORGANS         1127 

erection  of  the  penis,  the  male  orf^an  of  copulation.  It  is  composed 
chiefly  of  cavernous  tissue  which  is  arranged  in  three  long  and  some- 
what cylindrical  masses,  forming  the  corpus  spongiosum  below  and 
the  two  cor{>ora  cavernosa,  one  on  each  side,  above.  The  former  is 
traversed  l\v  the  urethra  and  terminates  anteriorly  in  a  conical  struc- 
ture, the  glans  penis.  Extei'nally,  these  bodies  are  enveloped  by 
fibrous  sheaths  and  a  thin  laycn-  of  very  movable  and  distensible  skin, 
which  is  then  reflected  upon  the  glans  penis  to  form  the  prepuce. 
The  erectile  tissue  of  which  these  bodies  are  composed,  is  made  up  of 
cavernous  spaces  which  are  really  venous  sinuses  lined  with  a  layer 
of  flattened  epithelium.  Their  walls  consist  of  membranous  parti- 
tions which  arc  derived  from  the  external  fibrous  investment,  the  tunica 
albuginea,  as  well  as  from  the  median  septum  of  the  penis.  In  this 
way,  a  spongy  network  of  connective  tissue  is  formed  which  is  much 
denser  near  the  circumference  than  near  the  center.  The  central 
spaces,  therefore,  are  larger  than  the  outer  ones,  but  all  of  them  are 
supplied  with  blood  from  branches  of  the  internal  pudendal  artery 
through  capillaries  which  are  rather  more  widely  open  than  those  of 
other  tissues. 

The  erection  of  this  tissue  is  dependent  upon  a  dilatation  of  these 
afferent  channels  through  which  the  blood  is  then  poured  freely  into 
the  lacunae,  but  since  the  venous  collecting  tubules  begin  with  a  nar- 
row orifice  which  is  strengthened  by  rings  of  smooth  muscle  tissue, 
the  offlow  is  somewhat  hindered  both  in  a  mechanical  way  as  well  as  by 
an  active  constriction  of  these  sphincters.  Consequently,  the  erection 
of  the  penis  cannot  be  regarded  as  a  pure  vaso-dilator  phenomenon, 
but  as  an  active  venous  retardation  which  is  brought  about  chiefly  by 
the  contraction  of  those  muscle  cells  with  which  the  outlets  of  the 
several  blood-spaces  are  beset.  In  addition,  it  is  entirely  probable  that 
the  action  of  this  intrinsic  muscle  tissue  is  materially  strengthened  by 
the  contraction  of  certain  extrinsic  muscles,  such  as  the  ischio  and 
bulbo-cavernosi.  By  compressing  the  larger  collecting  channels, 
these  muscles  tend  to  raise  the  venous  pressure  without  actually 
blocking  the  return  of  the  blood.  Meanwhile,  the  inner  walls  ofthe 
cavernous  spaces  are  fully  exposed  to  the  arterial  blood-pressure,^  which 
causes  them  to  move  outward  as  far  as  their  tough  fibrous  constituents 
as  well  as  the  fibrous  investment  of  the  entire  organ  will  allow. 

The  length  of  time  during  which  copulation  must  be  continued  in 
order  to  give  rise  to  an  ejaculation  of  the  semen  differs  greatly  with 
the  condition  and  type  of  the  animal.  It  is  safe  to  assume,  however, 
that  the  erection  of  the  penis  cannot  be  attained  by  vaso-dilatation 
alone,  because  a  reaction  of  this  kind  is  neither  sufficiently  intense  nor 
lasting.  Nor  can  it  be  due  to  venous  stagnation  alone,  because  the 
erected  organ  does  not  become  cyanosed  and  retains  a  higher  tempera- 
ture throughout  this  act.  These  facts  unmistakably  point  toward  a 
more  copious  blood  supply  and  greater  through-flow  and  not  merely 

1  Fran^-ois-Frank,  Arch,  de  Physiol.,  1895,  122. 


1128  THE  REPRODUCTIVE  ORGANS 

toward  a  more  abundant  content  in  blood  at  any  one  time.  This  con- 
clusion is  strengthened  by  the  fact  that  in  priapismus  this  organ  may 
retain  its  erected  condition  for  hours  and  even  for  days  without  show- 
ing an  actual  unpairment  of  its  tissues  or  gangrene.  Naturally,  the 
size  and  shape  of  the  erected  organ  are  determined  not  only  by  the  dis- 
tention of  the  cavernous  spaces,  but  also  by  the  arrangement  of  its  gross 
anatomical  structures,  such  as  its  dorsal  fascia  and  the  fascia  situated 
in  the  vicinity  of  its  base.  The  former  acts  in  the  manner  of  a  ligament. 
Since  it  is  shorter  than  the  one  investing  the  under  surface  of  this 
organ,  the  dorsal  aspect  of  the  erected  penis  must  exhibit  a  decided 
concavity.  This  change  in  its  shape  imparts  to  it  a  greater  penetrating 
power  and  increases  its  receptive  power  to  stimuli,  because  it  tends  to 
retract  the  prepuce  and  to  uncover  the  tactile  receptors  of  the  glans 
penis.  During  this  period  it  is  quite  impossible  to  void  urine,  because 
the  sphincter  vesicae  remains  firmly  closed.  Not  until  the  erection 
has  ceased  does  this  sphincter  regain  its  power  of  relaxation.^ 

The  reflex  center  controlling  this  act  is  situated  in  the  lumbar 
segment  of  the  spinal  cord.  The  corresponding  autonomic  fibers 
leave  this  structure  in  the  first  to  third  sacral  nerves  to  form  the  pelvic 
plexus  and  nervi  erigentes  and  cavernosi.  The  fact  that  the  latter 
contain  vaso-dilator  fibers  to  the  penis  has  been  proved  by  Eckhard, 
Loven  and  others  by  stimulating  them  electrically.  Afferently,  this 
reflex  center  may  be  activated  by  stimuli  applied  to  the  genitals 
directly,  as  well  as  by  stunuli  received  from  other  sense-organs  and  the 
cortical  association  centers. 

The  Act  of  Ejaculation. — The  discharge  of  the  semen  is  initiated 
by  a  powerful  peristalsis  of  the  vas  deferens,  seminal  vesicles  and 
ejaculatory  duct  which  forces  the  secretion  into  the  urethra.  Here  it 
is  prevented  from  entering  the  deeper  urethra  by  the  sphincter  vesicse^ 
and  is  mixed  with  the  secretions  of  the  prostate  and  Cowper's  glands. 
The  latter  are  poured  into  the  urethra  in  the  hollow  at  each  side  of 
the  colliculus  seminalis.  Then  begin  the  rhythmic  contractions  of 
certain  striated  muscles  which,  however,  are  not  under  the  control 
of  the  will.  Chiefly  involved  in  this  process  are  the  ischio-cavernosus, 
the  bulbo-cavernosus  and  the  sphincter  urethras  membranaceae  or 
sphincter  of  Henle. 

The  act  of  ejaculation  is  controlled  by  a  reflex  center  which  is 
situated  in  the  lumbar  segment  of  the  spinal  cord.  The  latter  may  be 
activated  by  afferent  stimuli  arising  in  the  genital  organs  and  evoked 
chiefly  in  Krause's  corpuscles  with  which  the  glans  penis  is  abundantly 
supplied.  Other  sense-organs,  such  as  the  general  cutaneous  receptors, 
the  retina,  and  organ  of  Corti  may  also  be  involved,  but  only  in  so  far 
as  their  impressions  give  rise  to  erotic  associations.  In  the  absence 
of  peripheral  stimuli,  the  activation  of  the  psychic  centers  may  lead  to 
"spontaneous"  emissions,  those  occurring  in  consequence  of  dreams 

1  Zeiss!  and  Holzknecht,  Wiener  med.  Blatter,  1902. 

2  Walker,  Archiv  ftir  Anatomie,  1899. 


THE    MALE    AND    FEMALE    IlEPRODTT'TrV'E    ORGANS  1129 

brinp;  called  pollutions.  Among  the  norvcs  (;oncornod  in  the  acts  of 
erection  and  ejaculation  may  be  mentioned  the  nervus  pudendus, 
nervus  erigens,  and  nervus  ileo-inguinalis.  The  first  sends  one  of 
its  branches,  the  nervus  perinei,  to  the  ischio  and  bulbo-cavernosi, 
the  bulbus  urethra?  and  the  mucous  membrane  of  the  upper  urethra. 
This  nerve,  therefore,  is  the  one  controlling  ejaculation.  Another  of 
its  branches,  the  nervus  dorsalis  penis,  innervates  the  skin,  prepUcc, 
corpora  cavernosa,  and  outer  portion  of  the  urethra.  This  nerve, 
therefore,  conveys  sensory  impulses  from  the  largest  part  of  the  penis. 
The  nervus  erigens,  as  has  been  stated  above,  is  chiefly  vasomotor  in 
its  function,  while  the  ileo-inguinalis  innervates  the  base  of  the  penis. 

The  Ovaries. — The  essential  reproductive  organ  of  the  female  is 
represented  by  the  ovaries,  two  flattened,  more  or  less  almond-shaped 
bodies  which  are  situated  in  the  uppen*  part  of  the  pelvic  cavity  in  a 
slight  depression  in  the  obturator  muscle.  Although  subject  to  con- 
siderable fluctuations,  the  adult  ovary  measures  2.5  to  5  cm.  in  length, 
1.5  to  3  cm.  in  breadth,  and  0.6  to  1.5  cm.  in  thickness.  In  cross- 
section  each  organ  is  seen  to  be  made  up  of  two  portions,  a  cortex  and 
a  medulla.  The  former  varies  in  thickness,  becoming  thinner  with 
advancing  years,  and  consists  of  connective  tissue  containing  isolated 
primordial  and  Graafian  follicles.  The  central  medullary  portion  is 
made  up  of  loose  connective  tissue  containing  large  numbers  of  blood- 
vessels and  smooth  muscle  cells.  ^ 

In  the  child,  the  greater  portion  of  the  ovary  is  composed  of  cortical 
substance  which  is  closely  packed  with  primordial  follicles  in  different 
stages  of  development.  This  is  also  true  of  the  ovary  of  young 
women,  but  the  follicles  are  then  more  widely  separated  from  one  an- 
other by  layers  of  connective  tissue  of  varying  thickness.  Each 
follicle  consists  of  an  oocyte  surrounded  by  a  single  layer  of  epithelium 
and  measuring  from  48  to  69  ju  in  diameter.  At  birth  each  ovary 
contains  at  least  100,000  oocytes,  while  at  puberty  it  embraces  only 
from  30,000  to  40,000;  but  even  this  number  is  more  than  sufficient  to 
supply  the  necessary  ova  for  fertilization,  because  only  one  of  them  is 
discharged  during  each  menstrual  period.  It  may  also  happen  that 
one  of  these  follicles  contains  two  and  more  distinct  ova,  a  fact  which 
has  been  made  use  of  in  explaining  multiple  pregnancies. 

These  primordial  follicles  eventually  develop  into  the  mature  Graafian  follicle, 
a  process  which  begins  at  birth  and  does  not  cease  until  the  menopause  has  termi- 
nated the  sexual  life.  To  begin  with,  the  spindle-shaped  epithehal  investment  is 
changed  into  a  single  layer  of  cuboidal  cells  which  then  proliferate  rapidly  until 
the  central  ovum  has  become  enveloped  by  several  layers  of  epithelial  cells.  By  the 
degeneration  of  certain  ones  of  these  cells  a  space  is  eventually  formed  around  the 
ovum  which  becomes  filled  with  fluid,  the  liquor  foUiculi.  The  o\'um  itself  grows 
larger  constantly  and  is  gradually  pushed  to  one  side,  where  it  becomes  surrounded 
by  a  layer  of  cells,  forming  the  discus  proligerus.  Its  nucleus  undergoes  important 
changes  which  finally  terminate  in  the  formation  of  the  first  polar  body,  a  deposi- 
tion of  yolk  granules  in  the  cytoplasm,  and  the  formation  of  a  thin  investment,  the 

1  Clark,  Contrib.  to  the  Science  of  Med.,  Johns  Hopkins  Univ.,  1900. 


1130 


THE   REPRODUCTrS'E    ORGANS 


zona  pellucida.     The  entire  follicle  is  marked  off  against  the  now  very  vascular 
connective  tissue  stroma  by  the  membrana  granulosa. 

The  Mature  Graafian  Follicle. — Beginning  shortly  after  birth, 
the  developing  primordial  follicles  pass  from  the  inner  realm  of  the 
cortex  toward  its  periphery,  but  do  not  actuall}"  reach  the  surface. 
Later  on,  however,  the  more  superficial  ones  pursue  the  same  course 
and  actuall}'  appear  externally  in  the  form  of  projecting  vesicular 
bodies,  the  diameter  of  which  varies  between  2  and  15  mm.  The  outer 
wall  of  these  vesicles  is  thin  and  nearly  bloodless  (stigma),  while  their 
remaining  investment  is  really  more  vascular  than  previously.  At 
this  time,   therefore,   the  projecting   Graafian  follicle   consists  of  a 


Fig.  537. — Gra-^flvx  Folucle  of  M.\mmaliax  CK-.vry. 
ov.  Ovum;  dp,  discus  proligerus;  Iq.f,  liquor  folliculi;  ch,  theca;  gr.  membrana  granu- 
losa.     (Prenant  and  Bouin.) 


connective  tissue  investment,  or  theca  follicula,  an  epithelial  covering, 
or  membrana  granulosa,  the  ovum,  and  the  liquor  folliculi.  The  o\Tim 
itself  now  measures  0.2  mm.  in  diameter,  as  against  48  to  69  /x  when 
first  formed,  and  contains  large  numbers  of  irregularly  shaped  and 
highly  refractive  granules,  the  so-called  deuteroplasm.  Its  nucleus 
or  germinal  vesicle  presents  a  well  differentiated  nucleolus,  or  germinal 
spot.  It  is  also  of  interest  to  note  that  the  connective  tissue  stroma 
gives  rise  at  this  time  to  a  peculiar  tj^pe  of  cells  which  contain  a  yel- 
lowish pigment  and  are  destined  to  play  an  important  role  later  on 
in  the  formation  of  the  corpus  luteum. 


THE  MALE  AND  FEMALE  KEPKODUCTWE  OHGANS    1131 

The  Corpus  Luteum. — According  to  Clark, ^  the  rupture  of  the 
Graafian  follicle  is  brougiit  about  by  complex  changes  in  the  vascu- 
larity of  the  ovary,  leading  to  a  congestion  of  the  entire  organ.  In 
consequence  of  this  increased  tension,  the  follicle  is  pushed  far  out- 
ward. The  stigma  of  its  outer  wall  becomes  necrotic  and  bursts, 
allowing  the  liquor  as  well  as  the  ovum  and  a  part  of  the  torn  mem- 
brana  granulosa  to  escape  into  the  tube.  The  walls  of  the  empty 
follicle  then  collapse,  but  are  distended  again  by  blood  derived  from 
the  vessels  of  the  theca.  To  begin  with,  therefore,  the  corpus  luteum 
is  represented  by  a  ruptured  Graafian  follicle,  filled  with  blood  and 
invested  by  a  layer  of  yellow  lutein  cells  of  the  theca.  The  latter 
multiply  rapidly  and  presently  enter  the  hemorrhagic  extravasate 
which  they  occupy  completely  with  the  exception  of  a  small  central 
area.  Connective  tissue  strands  and  blood-vessels  follow  them  in 
increasing  numbers  so  that  the  corpus  finally  assumes  the  appear- 
ance of  an  organized  and  growing  structure.  Very  soon,  however, 
retrogressive  changes  set  in  which  terminate  in  a  hyaline  degeneration 
of  the  lutein  cells  and  their  final  absorption.  This  obliteration  of  the 
corpus  luteum  takes  place  more  rapidly  in  young  persons,  because  the 
circulation  of  the  adult  ovary  has  lost  much  of  its  original  vigor. 
Eventually,  the  corpora  appear  merely  as  small  whitish  granules 
resembling  scar  tissue.  They  are  then  known  as  the  corpora  fibrosa  or 
albicantia.- 

It  is  to  be  emphasized,  however,  that  it  is  not  real  scar  tissue;  in 
fact,  the  reason  for  the  formation  of  the  corpora  lutea  is  to  prevent 
the  conversion  of  the  ovarian  parenchyma  into  a  tissue  of  this  type 
which  would  effectively  prevent  the  formation  and  discharge  of  other 
ova.^  Besides,  the  corpus  luteum  seems  to  furnish  an  internal  secre- 
tion which  is  intimately  concerned  with  the  future  development  of  the 
ovum.^  Thus,  it  has  been  noted  by  Frankel  that  the  next  succeeding 
menstruation  invariably  fails  to  take  place  if  the  corpus  luteum  has  pre- 
viously been  destroyed  by  means  of  a  cautery.  Further  evidence  to 
show  that  it  is  a  temporary  gland,  is  presented  by  the  fact  that  its 
atrophy  and  degeneration  are  closely  connected  with  the  fertilization 
of  the  ovum.  If  the  latter  is  not  fertilized,  this  retrogression  will  be 
completed  in  the  course  of  2  or  3  weeks,  while  if  it  is  fertilized,  the 
consummation  of  this  process  may  require  6  months  and  longer.  For 
this  reason,  it  is  customary  to  speak  of  true  and  false  corpora  lutea. 
The  former  is  larger  and  persists  until  the  development  of  the  ovum  is 
well  advanced,  whereas  the  latter  is  fully  reduced  within  a  short  time 
after  the  menstrual  period.  According  to  Miller,  it  is  possible  to  dis- 
tinguish between  these  corpora  by  histological  and   micro-chemical 

*  Johns  Hopkins  Hosp.  Rep.,  1898. 

2  Frankel,  Archiv  fiir  Gynec,  Ixviii,  1903,  438,  and  xci,  1910,  705;  also:  Meyer, 
ibid.,  c,  1913,  1,  and  Ruge,  ibid.,  c,  1913,  20. 

3  Marshall,  Physiol,  of  Reproduction,  London,  1910. 
^  L.  Loeb,  Jour.  Am.  Med.  Assoc,  xlvi,  1906,  416. 


1132  THE  REPRODUCTIVE  ORGANS 

means,  because  neutral  fat  is  readily  demonstrable  in  the  corpus  luteum 
of  menstruation. 

Menstruation. — The  process  of  menstruation  is  a  periodic  change 
in  the  life  cycle  of  the  female  which  is  most  plastically  betrayed  by  a 
discharge  of  blood  from  the  genitals,  derived  chiefly  from  the  mucous 
membrane  of  the  uterus.  In  general,  it  may  be  said  that  this  phenome- 
non appears  for  the  first  time  at  puberty  and  is  continued  thereafter 
at  intervals  of  28  days  until  about  the  forty-fifth  year.  This  statement 
would  imply  that  it  begins  in  temperate  climates  at  about  the  twelfth 
year  and  in  cold  climates  at  about  the  fifteenth  year,  but  much  depends 
upon  the  physical  condition  of  the  individual  as  well  as  .upon  her  sexual 
development  and  mode  of  life.  Thus,  we  are  reminded  at  this  time 
of  the  child-woman  of  certain  sections  of  India,  where  menstrua- 
tion is  regarded  as  a  disgrace  and  where  corresponding  measures  are 
taken  to  prevent  it  with  not  especially  flattering  results  to  the  off- 
spring nor  to  the  mother.  In  fact,  Haller  mentions  a  case  of  a  child- 
mother  who  menstruated  regularly  from  her  second  year  and  gave  birth 
to  a  child  at  the  age  of  nine. 

Before  the  first  menstrual  period,  the  approaching  sexual  maturity 
betrays  itself  by  a  more  rapid  growth.  The  pelvis  assumes  a  typically 
feminine  shape,  the  mammae  become  enlarged  and  hair  begins  to  grow 
upon  the  genitals  as  well  as  in  the  axillae.  Although  prone  to  be  irregu- 
lar at  first,  the  menses  are  repeated  as  a  rule  every  28  days, 
but  certain  variations  in  this  time  are  by  no  means  uncommon.  The 
hemorrhagic  discharge  sets  in  slowly,  reaches  a  maximum  about  the 
second  or  third  day,  and  then  gradually  subsides.  Consequently,  not 
more  than  4  or  5  days  are  usually  consumed  by  it.  In  our 
country,  menstruation  ceases  at  about  the  forty-fifth  year,  but  it  has 
been  noted  to  disappear  as  early  as  the  twenty-eighth  year  and  as  late 
as  the  sixty-third  year.  It  is  by  no  means  a  rare  occurrence  that 
women  of  fifty  and  over  bear  children.  The  cessation  of  the  menstrual 
flow  is  the  expression  of  a  series  of  changes  constituting  the  menopause. 
Underlying  these  changes  are  a  series  of  important  metabolic  altera- 
tions, the  completion  of  which  often  requires  several  years  and  renders 
the  woman  particularly  susceptible  to  pathological  processes  of  all 
kinds.  During  the  period  intervening  betvveen  puberty  and  the  meno- 
pause, conception  may  take  place  at  any  time.  In  rare  instances, 
however,  this  result  has  also  been  known  to  have  been  attained  long 
before  sexual  maturity  as  exemplified  by  the  changes  just  enumerated. 
Menstruation  ceases  immediately  upon  conception  and  does  not  recur 
until  after  the  termination  of  the  periods  of  pregnancy  and  lactation.^ 

The  discharge  of  blood,  however,  does  not  actually  constitute  the 
menstrual  period.  It  really  begins  several  days  beforehand,  and  is 
ushered  in  by  a  feeling  of  fatigue,  pains  in  the  back,  headache,  an 
increased  irritability  of  the  nervous  system,  an  unusual  tenseness  and 
sensitiveness  of  the  mammae,  a  congestion  of  the  vulva,  and  a  more 

^  Ploss,  Das  Weib  in  der  Natur  und  Volkerkunde,  Leipzig,  1894. 


THE  MALE  AND  FEMALE  REPRODUCTIVE  ORGANS    1133 

copious  soorotion  of  vaginal  fluifl  and  mucus.  These  premonitory 
symptoms  are  followed  by  a  hemorrhagic  oozinjjj  and  later  on  by  a 
period  of  restitution  which  occupies  almost  two  weeks.  Consequently, 
only  a  few  days  of  absolute  functional  rest  intervene  between  the 
successive  mcuistrual  cycles. 

The  division  of  this  process  into  the  periods  of  premenstruation, 
menstruation,  restitution,  and  complete  rest  leads  us  to  suspect  that 
the  endometrium  of  the  uterus  retains  a  comparatively  normal  appear- 
ance only  during  th(>  last  stage  of  restitution  and  th(^  succeeding  period 
of  rest.^  During  the  premenstrual  state  it  presents  distinct  evidences 
of  proliferation,  swelling  and  hypersecretion.  The  cells  of  the  stroma 
lose  tlieir  elongated  shape  and  become  more  rounded.  The  capillaries 
are  greatly  distended  with  blood  which  in  turn  gives  rise  to  a  hyper- 
plasia of  the  uterine  glands.  A  few  days  later  blood  begins  to  escape 
from  the  superficial  vessels  and  forces  its  way  into  the  lumen  of  the 
uterine  canal,  and  through  the  constricted  orifice  of  the  cervix  into 
the  vagina.  But  this  hemorrhagic  extravasation  is  not  associated  with 
any  considerable  destruction  of  tissue;  in  fact,  the  uterine  lining  re- 
mains rather  intact,  although  it  may  be  perforated  here  and  there  and 
even  partially  loosened  from  the  underlying  layers  by  spaces  which  are 
filled  with  blood.  In  most  instances  this  congestion  also  involves 
the  tubes,  ovaries  and  external  genitals,  but  these  organs  do  not  con- 
tribute to  the  hemorrhagic  discharge  and  hence,  menstruation  is  to 
be  regarded  essentially  as  a  phenomenon  of  the  uterus.  The  quantity 
of  blood  lost  during  this  period  may  amount  to  as  much  as  100  to  300 
grams. 2  Under  ordinary  conditions,  however,  it  is  mixed  with  consid- 
erable quantities  of  mucus,  which  substance  tends  to  preserve  the 
thrombocytes  and,  therefore,  to  prolong  the  coagulation-time.  Men- 
strual blood  as  such  clots  as  readily  as  any  other  type  of  blood. 

The  phenomenon  of  heat  exhibited  by  the  lower  mammals  is  the  homologue 
of  menstruation.  It  is  commonly  divided  into  four  periods,  namely:  (a)  the  pro- 
estrum,  during  which  the  organs  become  congested  and  bleed,  {b)  the  estrum,  or  stage 
of  sexual  desire,  (c)  the  metestrum,  or  period  of  restitution,  and  (d)  the  anestrum, 
or  stage  of  rest.  Contrary  to  the  human  female,  those  of  the  other  mammals  take 
the  male  only  during  the  estrus.  If  sexual  union  or  conception  is  prevented  at 
this  time,  the  period  for  sex-ual  intercourse  gives  way  to  the  period  of  restitution, 
but  recurs  again  after  a  definite  interval  which  in  bitches  is  12  to  16  weeks,  in  the 
cow  3  to  4  weeks,  in  the  sheep  2  to  4  weeks,  in  monkeys  about  4  weeks,  and  in  the 
sow  9  to  18  days. 

Relation  Between  Menstruation  and  Ovulation. — Among  the 
many  theories  proposed  to  explain  the  cause  of  menstruation  is  the 
older  view  that  the  menstrual  flow  is  the  female  fluid  of  fertilization. 
Subsequent  to  the  establishment  of  the  fact  that  menstruation  occurs 
in  periodic  cycles,  it  was  then  beheved  that  it  is  brought  on  by  the  ma- 

'  Findley,  Anat.  of  the  meiLstr.  uterus,  Am.  Jour.  Obst.,  xlv,  1902,  and  Hitsch- 
mann  and  Adler,  Bau  der  Uterusschleimhaut,  Manatsh.  fur  Geb.  und  Gyn.,  xxvii, 
1907. 

-  Hoppe-Seyler,  Zeitschr.  fiir  physiol.  Chemie,  xlii,  1904,  545. 


1134  THE  REPRODUCTIVE  ORGANS 

turing  of  the  Graafian  follicle  and  the  discharge  of  the  ovum.  Pfliiger' 
sought  its  cause  in  a  reflex  extravasation  of  blood  evoked  by  the  pres- 
sure which  the  growing  follicle  exerts  upon  the  nerves  of  the  ovary. 
This  view,  however,  was  put  into  question  by  the  clinical  experience 
that  ovulation  and  even  pregnancy  may  result  before  the  first  menstrua- 
tion as  well  as  after  the  menopause. ^  It  was  also  noted  that  conception 
may  take  place  during  the  period  of  lactation,  whereas  the  menstrual 
flow  is  then  usually  absent.  Lastly,  it  has  been  observed  by  Rein^  that 
pregnancy  is  possible  in  dogs  even  after  all  the  nerves  connecting  the 
uterus  with  the  spinal  cord  have  been  divided.  Certain  experiments 
are  also  at  hand  to  show  that  menstruation  does  not  cease  after  the 
transplantation  of  the  ovaries  into  some  other  part  of  the  body,  while 
ovulation  is  then  unpossible.  In  1871,  Sigismund  advocated  the  view 
that  menstruation  succeeds  ovulation  and  is  the  direct  result  of  the 
failure  of  the  ovum  to  become  fertilized.  It  has  also  been  stated  that 
menstruation  is  a  process  of  purification  and,  therefore,  serves  to  clean 
out  the  uterus  and  to  establish  a  proper  substratum  for  the  fertilized 
ovum  to  grow  upon.* 

Subsequent  to  the  development  of  the  hormone  doctrine,  FrankeP 
proposed  the  theory  that  menstruation  is  dependent  upon  the  forma- 
tion of  an  internal  secretion  by  the  corpus  luteum  which  controls  the 
blood  supply  of  the  ovary.  ^  He  believed  ovulation  to  be  related  to 
this  process  only  in  so  far  as  the  escape  of  the  ovum  initiates  the  forma- 
tion of  the  corpus  luteum  which  attains  its  full  development  about  7 
days  later,  i.e.,  at  a  time  when  menstruation  sets  in.  Consequently, 
ovulation  must  take  place  19  days  after  the  last  menstrual  flow. 
This  explanation  has  many  points  in  its  favor,  and  may  be  supported 
by  strong  clinical  evidence.  In  the  first  place,  it  is  obvious  that  men- 
struation is  dependent  upon  some  activity  of  the  ovaries,  because  the 
removal  of  these  organs  gives  rise  to  an  artificial  menopause  which  is 
characterized  by  a  cessation  of  the  menses  and  an  atrophy  of  the 
uterus.  Secondly,  this  cessation  of  the  menstrual  flow  does  not  result 
if  the  ovaries  are  transplanted  into  the  uterus  or  elsewhere  in  the 
abdominal  cavity.''  Thirdly,  menstruation  may  be  made  to  recur  by 
grafting  a  piece  of  an  ovary  in  the  uterus  or  under  the  skin  of  the 
abdomen,*  and  a  temporary  condition  of  estrus  may  be  incited  in 
mature  animals  by  the  injection  of  an  extract  of  ovaries  taken  from 

1  Bedeutung  and  Ursache  der  Menstruation,  Berlin,  1865. 

2  Berliner  klin.  Wochenschrift,  1871. 

3  Pfluger's  Archiv,  xxiii,  1880,  68. 

*  Bryce  and  Teacher,  Early  development  of  the  human  ovum,  190S. 
8  Archiv  fur  Gyn.,  1910. 

*  The  dried  extract  of  the  corpora  lutea  of  cows  is  made  use  of  in  the  treatment 
of  suppressed  menstruation  and  the  grave  symptoms  sometimes  following  the 
removal  of  the  ovaries  and  premature  production  of  the  menopause. 

'  Halban,  Deutsche  Gesellsch.  fiir  Gyn.,  ix,  1901;  also:   Glass,  Medic.   News, 
1899,  and  Morris,  Med.  Rec,  1901. 
8  Meredith,  Brit.  Med.  Jour.,  1904. 


THE    DEVELOPMENT    OF    THE    EMBRYO  1135 

an  animal  in  heat.'  Having  ostablishcKl  this  fact,  it  may  then  be 
proved  that  ovulation  is  not  synchronous  with  menstruation.  Thus, 
it  is  well  known  that  the  Mosaic  Law  regards  Jewesses  unclean  during 
the  menstrual  period  and  for  7  days  thereafter.  In  these  women, 
therefore,  conception  must  take  place  after  this  period  and  before  the 
onset  of  the  next  menstrual  flow.  Moreover,  Pinard^  has  shown  that 
about  three-fifths  of  the  women  who  marry  during  the  interim  between 
two  menstrual  periods  and  miss  the  subsequent  flow,  give  birth  to  full- 
term  children  280  days  after  the  beginning  of  the  last  menses.  In 
these  cases,  the  duration  of  pregnancy  is  less  than  9  calendar 
months.  Consequently,  if  ovulation  takes  place  some  time  before 
the  onset  of  the  menstrual  flow,  the  latter  must  be  in  the  nature  of  a 
process  of  purification  which  prepares  the  endometrium  for  the  suc- 
ceeding ovulation.  This  cyclic  regeneration,  therefore,  tends  to  keep 
the  uterine  membrane  in  a  condition  of  irritability  which  enables  it 
to  respond  very  promptly  to  the  stimulus  brought  to  bear  upon  it  by 
the  fertilized  ovum.  It  is  thus  in  the  best  possible  condition  to  de- 
velop the  decidual  membranes. 


CHAPTER  XCV 
THE  DEVELOPMENT  OF  THE  EMBRYO 

The  Migration  of  the  Ovum. — In  those  animals  in  which  the  ovary 
is  enveloped  by  a  peritoneal  pouch  into  which  the  Fallopian  tube 
opens,  no  special  difficulty  confronts  us  in  explaining  the  migration  of 
the  newly  formed  ovum  into  the  uterus.  In  those  animals,  on  the 
other  hand,  in  which  the  ovary  and  fimbriated  extremity  of  the  Fal- 
lopian tube  are  not  in  direct  contact  with  one  another,  we  are  forced  to 
assume  that  the  ovum  first  escapes  into  the  peritoneal  spaces  and  then 
enters  the  tube  from  without.  This  manner  of  migration  is  exemplified 
by  the  human  female.  Attention  was  first  called  to  this  possibility  by 
Bischoff,^  who  found  that  animals  possessing  bifurcated  or  bicornuated 
uteri  frequenth'-  present  corpora  lutea  in  the  ovary  opposite  to  that 
horn  of  the  uterus  in  which  the  embryos  are  developing.  Two  explana- 
tions may  be  offered  for  this  occurrence,  namely:  (a)  that  the  ovmn  has 
penetrated  the  tube  on  the  same  side  and  has  later  on  been  forced  into 
the  cornu  uteri  of  the  opposite  side,  and  (6)  that  it  has  migrated  to  the 
opposite  side  to  begin  with  and  has  then  entered  the  tube  and  uterine 
horn  of  the  same  side.     The  former  process  is  called  internal  migra- 

^  Marshall  and  Jolly,  Phil.  Transact.,  R.  Soc,  London,  1905. 
-  Ann.  de  gyn.  et  d'obst.,  1909. 

^  Die  Entwickelung  des  Kanincheneies,  1842;  also  Kussmaul,  Von  dem  Mangel, 
Verkiimmerung  und  tjberwanderung  des  Eies,  Wiirzburg,  1859. 


1136  THE    REPRODUCTIVE    ORGANS 

lion  and  the  latter,  external  migration.  Leopold^  has  proved  that  the 
latter  process  is  possible  by  excising  one  ovary  and  the  tube  of  the  op- 
posite side.  Many  of  these  animals  became  pregnant.  A  similar 
case  has  been  report(^d  by  Kelly,-  who  removed  the  diseased  left  ovary 
and  right  tube  of  a  woman,  leaving  the  right  ovary  and  left  tube  in 
situ.  Fifteen  months  after  the  operation,  this  woman  gave  birth  to  a 
normal  child.  Seventeen  months  later,  the  left  tube  had  to  be  re- 
moved for  the  relief  of  a  ruptured  extra-uterine  pregnancy.  Inas- 
much as  the  ovum  does  not  possess  an  inherent  power  of  movement, 
its  progress  must  be  determined  by  outside  forces,  such  as  gravity 
and  the  action  of  the  ciliated  lining  of  the  tube  and  uterus. 

While  much  uncertainty  prevails  regarding  the  manner  in  which 
the  ovum  gains  entrance  to  the  tube,  it  seems  established  that  ex- 
ternal migration  occurs  much  more  frequently  than  has  been  supposed. 
In  view  of  the  preceding  data,  it  would  seem  probable  that  the  ovum 
migrates  through  the  narrow  peritoneal  spaces  between  the  pelvic 
viscera  and  may  then  be  received  by  the  tube  of  the  same  side  as  well 
as  by  that  of  the  opposite  side. 

The  Migration  of  the  Spermatozoa. — In  the  male,  the  climax  of 
the  coitus  is  reached  with  the  ejaculation  of  the  semen  which  may 
or  may  not  occur  synchronously  with  the  orgasm  of  the  female.  The 
latter  betrays  itself  by  an  erection  of  the  clitoris  and  vaginal  folds,  a 
more  copious  secretion  of  vaginal  fluid  by  the  glands  of  the  vestibulum 
and  the  glands  of  Bartholini,  a  twitching  of  the  external  bands  of  vaginal 
muscle  tissue  (sphincter  vaginae),  and  an  alternate  depression  and 
elevation  of  the  uterus.  The  spermatozoa  deposited  in  the  seminal 
receptacle,  the  vagina,  find  their  way  into  the  uterus  by  their  own 
activity  which  consists  in  a  lateral  oscillatory  progression  of  the  head 
in  consequence  of  the  whip-like  action  of  the  tail.  The  latter,  how- 
ever, does  not  contract  as  a  whole  from  side  to  side,  but  in  the  manner 
of  the  tail  of  an  eel  (Fig.  535).  Under  favorable  conditions  the  speed 
attained  by  them  may  amount  to  4  to  10  mm.  in  a  minute.^  They  are 
aided  in  their  upward  movement  by  the  mucous  secretion  of  the  uterus 
which  attracts  them.  In  other  words,  this  secretion  exerts  a  positive 
chemotactic  influence  upon  them,  whereas  the  sour  vaginal  fluid 
affects  them  negatively.^  Secondly,  it  is  a  well-known  fact  that  the 
cilia  of  the  uterus  and  Fallopian  tubes  beat  in  a  direction  from  above 
downward  and,  therefore,  might  retard  the  progress  of  these  elements. 
This  is  not  so  actually,  because  the  spermatozoa  are  stimulated  by  these 
mechanical  impacts  to  greater  activity  and  are  capable  of  advancing 
even  against  the  direction  of  the  stream  of  the  intra-uterine  fluid. 
They  are,  therefore,  positively  rheotactic  and  thigmotactic. 

'^  Archiv  fiir  Gynec,  xvi,  1880,  22. 

2  Operative  Gynec,  ii,  1898,  187. 

^  Lott,  Anat.  und  Physiol,  des  Cervix  uteri,  Erlangen,  1871,  and  Henle,  Lehrb. 
der  Anat.,  Leipzig,  1890. 

^  Chrobak,  Wiener  klin.  Wochenschr.,  1901;  and  Low,  Stizungsb.  Wiener 
Akad.,    1902; 


THE    DEVELOPMENT    OF    THE    EMBRYO  1137 

Tho  fact  that  the  spermatozoa  arc  capaljlc  of  luakiiif^  their  own  way 
through  the  canal  of  the  cervix  into  tlie  uterus  is  proved  by  the  cases 
of  pregnancy  following  incomplete  coitus,  and  especially  by  the  preg- 
nancies which  have  occurred  in  women  possessing  perfect  hymens. 
Nevertheless,  it  has  been  thought  bv  Litzmann,  and  others,  that  the 
uterus  contracts  and  relaxes  at  the  height  of  the  orgasm  and  actually 
aspirates  the  semen  into  its  cavity.  Moreover,  Kristeller^  has  advo- 
cated the  view  that  a  mucus  plug  is  projected  at  this  time  from  the 
mouth  of  the  cervix,  which  is  then  retracted,  carrying  with  it  large 
numbers  of  spermatozoa. 

The  Place  of  Meeting  of  the  Ovum  and  Spermatozoa. — The  view 
that  the  fertilization  of  the  ovmn  is  effected  within  the  cavity  of  the 
uterus,  has  now  given  way  to  the  belief  that  the  meeting  between  the 
male  and  female  sperm-cells  takes  place  in  the  Fallopian  tube  and 
chiefly  in  its  funnel-shaped  outer  extremity.  Since  the  distance 
between  this  point  of  the  generative  tract  and  the  mouth  of  the  uterus 
measures  only  about  16  cm.,  the  spermatozoa  may  reach  this  receptacle 
in  less  than  1  hour.  In  fact,  the  occurrence  of  ovarian  pregnancy 
in  woman  demonstrates  that  these  elements  may  even  advance  as 
far  as  this  organ  and  that  the  fimbriated  extremity  of  the  tube  is  not 
absolutely  impermeable.  This  view,  that  impregnation  takes  place  in 
the  Fallopian  tube,  also  finds  substantiation  in  the  fact  that  living 
spermatozoa  have  frequently'  been  found  here;  in  fact,  they  have  been 
noted  to  live  within  its  lumen  for  an  almost  indefinite  period  of  time. 
In  the  tubes  of  the  bat,  for  example,  they  have  been  known  to  retain 
their  activity  for  many  months. 

The  Implantation  of  the  Ovum. — After  its  fertilization  the  ovum 
undergoes  repeated  segmentation  and  slowly  progresses  into  the  uterus 
where  it  remains  until  the  end  of  the  period  of  gestation.  It  tra- 
verses this  distance  in  about  8  days  after  its  impregnation,  ha\nng 
meanwhile  attained  a  diameter  of  0.2  mm.  and  completed  the  morula 
stage. 2  The  earliest  specimen  of  developing  ova  has  been  described 
by  Bryce  and  Teacher.^  It  measured  0.77  mm.  in  length  and  0.63 
mm.  in  breadth,  and  was  about  13  days  old.  This  one,  as  well  as  all 
the  others  representing  a  later  stage  of  development,  w^ere  found 
deeply  imbedded  in  the  decidua  and  hence,  well  removed  from  the 
cavity  of  the  uterus.  Spee,^  therefore,  assumes  that  the  human  ovum 
attaches  itself  to  the  free  surface  of  the  endometrium  and  destroys 
the  underlying  tissue  by  means  of  a  tryptic  ferment.^  In  this  way  it 
gradually  sinks  into  the  depth  of  the  uterine  decidua,  its  point  of 

'  Berliner  klin.  Wochenschr.,  1871. 

-  Grosser,  Vergl.  Anat.  und  Entwickelungsgesch.  der  Eihaute  und  Placenta, 
Leipzig,  1909. 

'  Early  development  and  imbedding  of  the  human  o\'nm,  Glasgow,  1908; 
also  Linzenmeier,  Archiv  fiir  Gynec,  cii,  1914,  1 

^Zeitschr.  fur  Morph.  und  Anthropol.,  1901,  and  Verh.  deutsch.  Ges.  fiir 
Gynec,  1906. 

^  Grafenberg,  Zeitschr.  fiir  Geburtshilfe  und  Gynec,  1910. 

72 


1138  THE    REPRODUCTIVE    ORGANS 

entrance  being  obliterated  very  soon  thereafter  by  the  coalescence  of 
the  edges  of  the  opening. 

Pregnancy. — With  the  descent  of  the  ovum,  the  woman  begins 
to  exhibit  very  characteristic  local  and  general  signs  of  pregnancy. 
The  virgin  uterus  is  small,  pear-shaped,  almost  solid,  and  only  6.5  cm. 
in  length.  At  the  end  of  pregnancy,  on  the  other  hand,  it  has  been 
converted  into  a  large  thin-walled  sac,  measuring  32  cm.  in  length, 
24  cm.  in  breadth,  and  22  cm.  in  depth.  Its  volume,  which  now 
amounts  to  5000-7000  c.c,  has  been  increased  519  times,  and  its  weight 
from  32  grams  to  1000  grams.  This  hjq^ertrophy  really  begins  with 
the  moment  of  conception,  and  while  all  of  its  elements  are  involved 
in  this  process,  it  affects  more  particularly  its  smooth  muscle-cells. 
The  latter  increase  not  only  in  their  length  and  thickness,  but  also  in 
their  number.  A  similar  proliferation  takes  place  in  the  elastic  tissue 
and  mucous  membrane,  which  attains  a  thickness  of  almost  0.5  cm. 
by  the  time  the  ovum  has  entered  the  uterine  cavity  and  of  0.75  cm. 
at  the  end  of  the  second  month  after  conception.  At  the  end  of  preg- 
nancy, the  uterine  wall  shows  an  average  thickness  of  only  3-5  mm. 
These  changes  account  for  the  fact  that  the  cervix  uteri  loses  its  firm 
and  almost  cartilaginous  consistency  within  a  few  weeks  after  con- 
ception. A  sunilar  change  is  noted  very  shortly  before  the  onset  of 
each  menstrual  flow. 

The  vascularity  of  the  ovaries  is  increased,  but  ovulation  ceases 
as  a  rule  during  pregnancy.  For  this  reason,  it  is  not  difficult  to 
detect  the  corpus  luteum  formed  in  the  place  of  the  impregnated 
ovum.  The  vaginal  wall  also  becomes  more  vascular  and  assumes  a 
peculiar  violet  color.  Its  tissue  is  strengthened  by  new  elements  and 
so  is  that  of  the  vulva.  Possibly  the  most  striking  change  is  exhibited 
by  the  mammae  which  alter  theu*  consistency  and  size  as  well  as  color. 
Already  during  the  second  month  of  pregnancy,  these  organs  become 
tense  and  nodular  and  are  permeated  by  numerous  large  veins  which 
are  sharply  outlined  against  the  lighter  glandular  tissue.  The  nipples 
increase  in  size,  become  more  erectile  and  assume  a  much  deeper 
color.  The  areola  surrounding  each  becomes  much  broader,  assumes 
a  darker  color,  and  acquires  numerous  globular  elevations  which  find 
their  origin  in  an  enlargement  of  the  sebaceous  glands.  Owing  to  the 
increased  distention  of  the  integument,  striae  may  be  formed 
which  closely  resemble  those  noted  in  the  wall  of  the  abdomen  of 
multipara.  This  enlargement  of  the  mammae  results  in  consequence 
of  the  discharge  of  a  specific  hormone  by  the  sexual  organs.  Quite 
aside  from  the  experiments  of  Claypon  and  Starling  upon  virgin  rabbits, 
which  have  been  cited  above  but  have  more  recently  been  criticized 
by  Frank  and  linger,^  this  conclusion  is  fully  justified  by  the  observa- 
tions of  Schants,^  upon  the  Blazek  sisters,  a  pygopagous  twin.     One 

1  Archiv  of  Int.  Med.,  vii  ,  1911,  812. 

2  Gynec.  Rundschau,  iv,  1910,  437. 


THE    DEVELOPMENT    OF    THE    EMBRYO  1139 

of  those  g,a\v  ])irth  to  a  child  which  was  subsequently  suckled  by  either 
with  (Hiually  beneficial  results. 

The  onlarRing  uterus  also  inflicts  certain  spatial  restrictions  upon  the  neighbor- 
ing pelvic  ami  abtloniiiial  organs.  Since  these  changes  arc  effected  chiefly  by  its 
fuiulus,  whereas  the  cervix  tends  to  retain  its  previous  size,  a  rather  acute  angle 
is  finally  formed  between  these  parts,  whichisaugincntcd  stillfurther  astiic  fundus 
progresses  ujjward  beyond  the  boundaries  of  the  jjolvis.  At  the  fourth  month  the 
upper  border  of  the  latter  lies  opposite  a  horizontal  line  drawn  midway  between  the 
umbilicus  and  the  symi)hysis  pubis,  at  the  end  of  the  sixth  month  opposite  the 
umbilicus,  and  at  the  end  of  9  months  almost  opposite  the  cnsiform  cartilage.  The 
intestines  are  forced  into  the  lateral  extents  of  the  abdominal  cavity,  so  that  the 
anterior  wall  of  the  uterus  comes  to  rest  against  the  anterior  wall  of  the  abdomen. 
The  linea  alba  is  broad  and  sharply  outlined  by  its  glistening  white  color.  It  need 
scarcely  be  emphasized  that  these  encroachments  are  responsible  for  a  whole  series 
of  far-reaching  reflex  actions. 

Among  the  latter  might  be  mentioned  the  vomiting  of  pregnancy,  minor  dis- 
orders of  digestion,  constipation,  and  stagnation  phenomena  in  the  biliary  passages.' 
The  kidneys  may  be  affected  directly  by  pressure,  as  well  as  indirectly  in  conse- 
quence of  various  disturbances  of  metabolism.  The  heart  is  displaced  and  its  area 
of  dulncss  increased.  The  latter  change  has  given  rise  to  the  statement  that  this 
organ  undergoes  at  this  time  a  mild  hypertrophy.^  The  pulse  rate  is  not  materially 
increased,  whereas,  the  pulse-pressure  and  total  work  of  the  heart  are  augmented 
in  a  considerable  measure.  The  respiratory  movements  are'somewhat  hindered, 
owing  to  the  upward  displacement  of  the  diaphragm,  but  the  total  interchange  of 
the  gases  is  rather  increased.  This  is  made  possible  by  a  broadening  out  of  the 
thorax.  A  moderate  hypertrophy  of  the  thj^roid  and  parathyroid  bodies  is  not 
uncommon  even  during  normal  pregnancy,^  and  a  similar  change  may  be  displayed 
by  the  hypophysis  and  the  cortex  of  the  adrenal  glands.*  Peculiar  yellowish 
discolorations,  the  so-called  chloasmae,  appear  in  different  regions  of  the  skin. 
The  pregnant  woman  also  displays  mild  mental  disturbances  which  are  associated 
with  an  increased  irritability  of  the  entire  nervous  system.  Thus,  she  may 
crave  for  the  most  unusual  articles  of  food  and  suffer  from  mental  depression 
and  all  sorts  of  imaginary  evils.  For  the  neuropathic  woman,  this  period  is  one  of 
danger,  because  these  mild  and  functional  psychoses  may  finally  develop  into  a 
permanent  or  true  psychosis. 

In  general,  however,  it  cannot  be  doubted  that  pregnancy  improves 
the  condition  of  the  woman,  and  while  this  change  may  not  be  appar- 
ent during  the  first  few  months,  it  certainly  makes  itself  felt  later  on.^ 
The  initial  period  of  fatigue,  lassitude  and  mental  depression  appears 
to  be  associated  with  the  rapid  depletion  of  her  energy  by  the  rapidly 
growing  embryo.  Later  on,  however,  when  a  more  stable  equilibrium 
has  been  established  by  the  development  of  greater  storative  qualities, 
her  health  improves  perceptibly.  This  is  especially  true  of  her  powder 
of  retaining  nitrogen  and  constructing  proteid  tissue,  which  in  turn 
leads  to  an  increase  in  her  weight  and  a  decrease  in  the  nitrogenous 
content  of  her  urine  from  its  previous  level  of  about  90  per  cent,  to 

1  Opitz,  Zeitschr.  fur  Geburtshilfe  und  Gynec,  Ixxii,  1913,  351,  and  Hofbauer, 
ibid.,  Ixi,  1908,  200. 

^  Jaschke,  Archiv  fiir  Gynec,  xciii,  1911,  809. 

^  Seitz,  Pnnere  Sekretion  und  Schwangerschaft,  Leipzig,  1913. 

*  Mayer,  Archiv  fur  Gynec,  xc,  1910,  600. 

°  Bar,  Lemons,  de  path,  obstetricale,  Paris,  1907. 


1140  THE  REPRODUCTIVE  ORGANS 

80  or  85  per  cent.     There  may  also  be  noted  a  slight  increase  in  the 
percentage  of  ammonia. 

The  Development  of  the  Placenta. — The  cytoplasm  of  the  ovum 
contains  a  certain  amount  of  nutritive  material  which,  however,  does 
not  last  for  a  longer  time  than  its  initial  period  of  growth.  Hence,  a 
new  source  of  supply  must  be  established  as  soon  as  the  ovum  has 
become  firmly  attached  to  the  maternal  tissues.  It  will  be  remembered 
that  the  defect  through  which  the  ovum  has  entered  the  uterine 
decidua,  closes  soon  afterward,  the  layer  of  tissue  now  investing  the 
ovum  externally  being  known  as  the  decidua  reflexa,  and  that  lining 
the  substance  of  the  uterus  as  the  decidua  vera.  Directly  under- 
neath the  developing  ovum  lies  the  decidua  basalis.  The  latter, 
together  with  the  enveloping  membranes  of  the  ovum,  now  enters  into 
the  formation  of  a  special  organ,  the  placenta,  the  purpose  of  which 
is  to  effect  an  interchange  of  materials  between  the  fetus  and  the 
mother.  Evidently,  this  structure  arises  from  a  union  of  certain 
fetal  and  maternal  tissues,  and  consists  essentially  of  vascular 
outgrowths  or  villi  of  the  chorion  of  the  fetus  which  become  approxi- 
mated to  large  blood  spaces  formed  in  the  decidua  basalis  of  the  uterus. 
Consequently,  the  blood  of  the  mother  does  not  actually  pass  into  the 
channels  of  the  fetus,  but  remains  separated  from  that  of  the  latter  by 
the  lining  of  the  blood-vessels  and  the  epithelial  layers  of  the  villi  of 
the  chorion. 

To  begin  with,  this  separation  is  effected  by  a  single  layer  of  cells  of  the  ectoderm 
and  constitutes  the  external  envelope  of  the  blastodermic  vesicle.  As  soon  as  the 
ovum  has  become  firmly  lodged  upon  the  decidua,  these  cells  proliferate  and  project 
outward  in  the  form  of  minute  finger-like  processes  or  villi,  which  impart  a  peculiar 
fringed  appearance  to  this  layer.  Each  villus,  therefore,  is  situated  upon  a  substra- 
tum of  connective  tissu-e  with  which  it  remains  connected  by  a  stalk,  and  consists 
of  an  outer  epithelial  covering  and  an  inner  framework  of  connective  tissue.  The 
cells  of  the  former  frequently  proliferate,  forming  additional  minute  buds  upon  the 
individual  villi.  It  is  also  to  be  noted  that  the  latter  are  very  numerous  in  that 
region  of  the  ovum  which  lies  most  directly  in  contact  with  the  basilar  decidua. 

Mention  should  also  be  made  of  the  amnion  which,  when  fully  formed,  com- 
pletely invests  the  emljryo,  and  eventually  comes  to  lie  in  close  contact  with  the 
inner  surface  of  the  chorion.  The  amnion  is  developed  as  two  layers,  an  external 
one  consisting  of  mesoderm  and  an  internal  one  composed  of  cuboidal  or  flattened 
ectoderm.  A  clear  fluid  then  collects  between  these  layers  which  gradually  increases 
in  quantity  as  pregnancy  progresses.  Its  average  amount  at  term  is  600  c.c.  and  its 
specific  gravity  1.002  to  1.028.  It  is  derived  chiefly  from  the  mother's  serum  by 
transudation  through  the  amniotic  epithelium, ^  but  may  also  contain  fetal  urine 
during  the  last  months  of  pregnancy  if  the  mother's  kidneys  become  defective.^ 
The  function  of  this  fluid  is  chiefly  protective,  because  it  serves  to  mitigate  the  force 
of  sudden  shocks  and  to  prevent  the  loss  of  heat  from  the  fetus  by  investing  its 
surface  with  a  medium  of  constant  temperature.  Secondly,  it  keeps  the  developing 
fetus  away  from  othertissuessothatitcannot  become  adherentto them.  Thirdly, 
it  may  supply  water  as  well  as  albumin  to  its  tissues.  Lastly,  it  serves  as  the 
normal  dilator  of  the  cervix  of  the  uterus  during  labor.     In  this  case,  it  acts  as  a 

1  Ahlfeld,  Zeifechr.  fur  Geb.  und  Gynec,  Ixix,  1911,  91. 

2  Wolff,  in  Oppenheimer's  Handb.  der  Bioch.,  iii,  1910,  709. 


* Iv      \    •        *,         '      -' 


Fig.  53S. — Diagrammatic  Representation  of  Rel.\tionship  of  Ovtm  to  Decidpa. 
1,  In  latter  half  of  first  week;  2,  a  few  days  later;  3,  a  few  months  lator,  when  placenta 
is  well  defined  (Webster) :  a,  Fetal  mesoblast,  sho-w-ing  indications  of  beginning  extension 
into  trophoblast  stalks  in  1,  actual  extension  in  2  and  3;  h,  trophoblast,  being  reduced  in 
3  and  constituting  here  the  layer  of  Langhans;  c,  trophoblast  lacuna  in  1,  enlarged  in  2 
and  3  as  an  inters-illous  space:  d,  syncytium,  seen  in  its  earliest  stage  in  1;  f,  decidua;  /, 
maternal  blood-sinus;  g,  endothelium  lining  maternal  sinus;  h,  epiblastic  covering  of  cord; 
i,  amniotic  epiblast;^,  umbilical  vein;  A-,  umbilical  arterv^  I,  amniotic  mesoblast;  m,  exten- 
sion cf  decidua  on  un<ier  surface  of  chorion  at  edge  of  placenta:  n,  large  villus-stem. 


THE  DEVELOPMENT  OF  THE  EMBRYO  1141 

rounded  bag  of  wntcr  and  tMial)li\s  the  contracting  uterus  to  l>rinn  an  equal  pressure 
to  bear  upon  the  entire  circumference  of  the  cervix,  tlierel)y  preventing  tears. 

The  Function  of  the  Placenta. — At  al)()iit  the  foinili  month,  this 
organ  consists  chieti}^  of  villi  of  the  chorion  which  contain  connective 
tissue  cells  and  numerous  blood-vessels.  The  cells  of  the  tips  of  these 
projections  proliferate  very  actively  and  finally  invade  the  decidua. 
The  spaces  Ijetween  these  projections,  as  well  as  those  separating  the 
individual  villi,  are  filled  with  maternal  blood,  which  gains  entrance 
to  them  through  free  openings  in  the  maternal  blood-vessels.  It  will 
be  seen,  then^fore,  that  the  maternal  blood  remains  separated  from 
that  of  the  fetus  by  the  double  layer  of  epithelium  of  the  chorion  and 
the  stroma  and  walls  of  the  blood-vessels  of  the  villi.  Consequently, 
the  placenta  really  represents  a  mass  of  maternal  blood  which  has 
been  temporarily  diverted  into  the  spaces  between  the  chorionic 
membrane  and  the  decidua  basalis  of  the  uterus.  Into  this  blood 
project  the  capillary  coils  of  the  different  villi,  without,  however, 
establishing  a  direct  connection  between  these  two  types  of  blood. 

Regarding  the  manner  in  which  the  constituents  of  one  are  inter- 
changed for  those  of  the  other,  nothing  further  can  be  said  than  has 
already  been  mentioned  when  discussing  the  causes  underlying  the 
formation  of  any  secretion.  Diffusion  and  osmosis  are  augmented 
by  a  vital  activity  of  the  lining  cells  of  the  chorionic  villi.  Evidently, 
these  cells  play  the  part  of  a  gland.  The  oxygen  and  nutritive  par- 
ticles are  made  to  pass  into  the  umbilical  vein  of  the  fetus,  w^hereas 
the  waste  products  of  the  latter  are  directed  from  the  capillaries  of 
its  two  umbilical  arteries  into  the  maternal  venous  system.  Fat 
globules  have  been  observed  to  traverse  the  chorionic  lining  cells 
and,  besides,  these  cells  serve  as  storehouses  of  glj^cogen,  from  which 
the  fetus  may  derive  extra  amounts  of  sugar  whenever  in  need  of 
them.  Attention  should  also  be  called  to  the  fact  that  considerable 
quantities  of  glycogen  are  deposited  in  the  uterine  mucosa  some  time 
before  each  menstrual  period,  a  provision  of  Nature  which  evidently 
is  made  in  anticipation  of  the  arrival  of  a  fertilized  ovum.  Thus,  it 
will  be  seen  that  the  placenta  really  represents  a  combination  of  organs, 
because  it  serves  jointly  as  the  respiratory,  digestive  and  excretory 
mechanisms  of  the  developing  young.  By  analogy  it  may  then  be 
concluded  that  the  fetus  really  occupies  the  position  of  a  tissue,  its 
nutrition  being  cared  for  as  if  it  were  an  actual  part  of  the  maternal 
body.  Practically  any  substance  contained  in  the  mother's  blood 
may  find  its  w^ay  into  the  fetus. 

Within  10  to  20  minutes  after  the  expulsion  of  the  fetus,  the 
placenta  is  cast  off  from  the  uterus,  forming  what  is  known  as  the 
after-birth.  The  latter  appears  as  a  flat,  rounded  plate,  weighing  500 
to  600  grams,  and  measuring  15  to  18  cm.  in  diameter  and  2  to  3  cm. 
in  thickness.  Its  outer  or  maternal  surface  is  rough  and  presents 
numerous  irregular  depressions,  or  cotyledons,  while  its  inner  or  fetal 
surface  is   covered  by  amniotic  membrane  and  possesses,  therefore, 


1142  THE  REPRODUCTIVE  ORGANS 

a  smooth  and  glistening  appearance.  The  umbihcal  cord,  containing 
the  blood-vessels  which  connect  the  fetus  with  the  placenta,  usually 
enters  near  its  center.  It  measures  1.0  to  2.5  cm.  in  diameter  and 
about  55  cm,  in  length.  Its  outer  envelope  consists  of  several  layers 
of  epithelium  which  are  directly  continuous  with  the  skin  of  the 
fetus.  Its  connective  tissue  reticulum  contains  a  mucoid  substance, 
known  as  the  Whartonian  jelly,  which  serves  as  a  protection  to  its 
blood-vessels.  The  latter  ramify  extensively  directly  below  the  sur- 
face of  the  amnion,  so  that  they  are  already  well  subdivided  before  ' 
they  reach  the  chorion. 

The  Nutrition  of  the  Embryo. — In  the  earliest  stage  of  its  develop- 
ment the  embryo  possesses  no  circulatory  system,  but  derives  its 
nutritive  material  from  the  media  surrounding  it.  Shortly  afterward 
there  is  developed  the  yolk-circulation  which,  however,  does  not 
continue  for  any  length  of  time,  because  the  supply  in  this  material 
is  very  limited.  For  this  reason,  its  place  is  taken  during  the  third 
week  by  the  circulatory  mechanism  of  the  chorion  which  is  eventually 
changed  into  the  complete  circulatory  system  of  the  placenta.  The 
latter  becomes  functional  at  the  end  of  the  second  month  of  intra- 
uterine life,  so  that  the  fresh  blood  henceforth  leaves  the  placenta  by 
way  of  the  umbilical  vein,  while  the  impure  blood  is  returned  to  it 
by  way  of  the  umbilical  arteries.  The  fetal  heart  beats  as  a  rule  at 
the  rate  of  120  to  140  in  a  minute.  It  may  be  heard  at  first  directly 
over  the  symphysis  pubis,  and  during  the  later  months  at  a  point 
about  midway  between  the  umbilicus  and  the  superior  iliac  spine, 
according  to  the  position  of  the  fetus.  ^  Actual  movements  of  the 
fetus  are  perceived  at  about  the  eighteenth  or  twentieth  week. 

The  oxygen  requirement  of  the  fetus  is  relatively  small,  because 
the  developing  organism  is  protected  against  a  loss  of  heat  by  the 
mother.  This  implies  that  the  heat  produced  in  consequence  of  the 
oxidations  in  its  tissues  is  stored,  giving  rise  to  a  temperature  which 
is  usually  somewhat  higher  than  that  of  the  mother.  As  far  as  the 
actual  transfer  of  oxygen  is  concerned,  it  has  been  proved  that  the 
blood  of  the  umbilical  vein  is  lighter  in  color  than  that  of  the  umbilical 
arteries,  and  contains  oxyhemoglobin.  In  this  connection  it  might 
also  be  mentioned  that  ether  and  chloroform,  when  administered  to 
the  mother,  are  transferred  to  the  fetal  blood. 

The  occurrence  of  a  transfer  of  nutritive  material  is  proved  con- 
clusively by  the  constant  growth  o£  the  fetus.  In  this  process  the 
chorionic  epithelium  plays  a  part  analogous  to  that  of  the  intestinal 
wall,  i.e.,  it  subjects  the  nutritive  substances  to  radical  changes  in 
order  to  render  them  assimilable  by  the  cells  of  the  fetal  tissues. 
This  is  true  of  the  albuminous  material  as  well  as  of  fats.  Both  are 
first  reduced  into  simpler  compounds  and  are  then  rebuilt  into  tissue- 
protein  and  body  fat.     In  the  case  of  the  fat,  Hofbauer^  has  shown  that 

^  First  heard  by  Mayor  of  Geneva,  in  1818. 

2  Zeitschr.  fur  Geburtsh.  unci  Gynec,  Ixiv,  1909,  668. 


THE  DEVELOPMENT  OF  THE  EMBRYO  1143 

whereas  fat  stained  with  Sudan-red  aetually  reaches  the  intervillous 
spaces,  it  reappears  as  unstained  globules  within  the  syncytium  of  the 
villi.  But  even  the  pigment  so  separated  traverses  these  cells  and 
circulates  in  the  fetal  blood.  Glycogen  is  found  in  all  the  tissues  of 
the  embryo  during  its  period  of  most  active  growth,  although  later  on, 
when  the  liver  becomes  functional,  it  disappears  almost  completely 
from  the  skin,  lungs  and  other  organs.  In  order  to  effect  these  reduc- 
tions and  syntheses,  the  chorionic  epithelium  must  be  in  possession  of 
different  enzymes,  an  assumption  which  has  moi-e  recently  found 
experimental  proof  in  the  work  of  Bergell  and  Folk,^  and  others. 
Thus,  the  especially  high  requirement  of  the  fetus  in  salts  may  bring  it 
about  that  the  bones,  and  particularly  the  teeth,  of  the  mother  become 
affected.  Some  women  are  more  prone  to  suffer  from  this  partial 
decalcification  than  others,  a  difference  which  seems  to  be  associated 
with  their  varying  power  of  assimilating  calcium  from  their  food. 

It  is  also  a  well-known  fact  that  drugs  may  be  transmitted  from 
the  mother  to  the  fetus,  as  well  as  in  the  reverse  direction.  This  is 
true  of  potassium  cj'anid,  alcohol,  strychnin,  and  many  inorganic 
and  organic  salts.  Bacteria  as  such  are  rarely  transferred,  so  that 
the  placenta  may  be  regarded  as  playing  the  part  of  a  filter.  This 
power  it  loses  if  diseased.  Neither  does  it  seem  to  be  able  at  any  time 
to  exclude  toxins. - 

Determination  of  Sex. — In  1897  Schenk  made  the  startling  claim 
that  the  nutrition  of  the  embryo  may  be  influenced  in  such  a  way  as 
to  produce  either  a  male  or  a  female  offspring.  This  speculation  he 
based  upon  the  older  view  which  contends  that  sex  is  dependent  upon 
the  nutritive  superiority  of  the  father  or  mother.  The  work  of  Rauber,^ 
Morgan,^  Wilson^  and  Doncaster,*^  however,  has  proved  that  sex  is 
determined  before  the  beginning  of  segmentation,  i.e.,  either  at  the 
time  or  immediately  after  the  union  of  the  sperm-cells.  The  actual 
factor  here  concerned  seems  to  be  the  spermatozoon  which  may  or 
may  not  embrace  an  accessory  chromosome.  Thus,  it  has  been  found 
that  the  spermatocytes  of  many  animals  contain  an  odd  number  of 
chromosomes,  while  in  the  oocytes  they  appear  in  pairs  and  are  ar- 
ranged in  a  similar  manner.  In  fact,  the  spermatocytes  are  said  to 
appear  in  three  forms,  namely :  (a)  one  in  which  a  centrosome  remains 
without  a  mate,  (6)  one  in  which  the  chromosomes  of  one  pair  differ 
in  size,  and  (c)  one  in  which  they  are  all  ahke.  The  reduction  in  the 
number  of  these  chromosomes  during  fertilization  must  then  give  rise 
to  three  types  of  spermatozoa,  namely:  (a)  one  in  which  an  odd  chro- 
mosome is  present,  {h)  one  in  which  the  number  of  the  chromosomes 
is  even  but  in  wdiich  a  small  or  aberrant  chromosome  is  present,  and 

^  Miinchener  med.  Wochenschr.,  1908. 

^  Lubarsch,  Ergebn.  der  allg.  Path,  und  path.  Anat.,  1896. 

'  tjberschuss  an  Knabengeburten  und  seine  biol.  Bedeutung,  Leipzig,  1900. 

*  Heredity  und  Sex,  New  York,  1913. 

^  Jour,  of  Exp.  Zoology,  iii,  1906,  and  Science,  1909. 

®  The  Determination  of  Sex,  Cambridge,  1914. 


1144  THE  KEPRODUCTIVE  ORGANS 

(c)  one  in  which  the  chromosomes  are  evenly  reduced  and  identical 
in  appearance.  If  either  one  of  tlie  first  two  varieties  fertilizes  the 
egg,  a  male  results,  whereas  that  variety  which  possesses  the  identical 
chromosomes  gives  rise  to  a  female. 

In  man,  the  number  of  the  chromosomes  is  given  as  23  and  24 
respectively.  The  first  type  of  spermatozoon  gives  rise  to  males  and 
the  second  to  females.  Consequently,  the  segmentation  nucleus 
must  contain  47  chromosomes  in  the  first  case  and  48  in  the  second. 
These  facts,  however,  explain  sex  only  and  do  not  show  why  the 
number  of  male  children  born  at  full  term  is  greater  than  that  of  the 
females.  The  ordinary  relationship  of  106  males  to  100  females  rises 
to  130:100  in  women  whose  first  children  were  born  after  they  had 
reached  their  thirtieth  year,  and  to  140  :  100  in  women  whose  first 
children  were  born  after  their  fortieth  year.  The  statistics  gathered 
more  recently  confirm  the  old  view  that  a  greater  number  of  males  are 
born  during  times  of  war. 

Parturition. — The  fetus  is  fully  developed  and  ready  to  be  expelled 
280  days  after  the  first  day  of  the  last  menstrual  period,  but  this  date 
is  only  approximate,  because  normal  children  are  also  born  as  early  as 
240  and  as  late  as  320  days  after  the  day  just  specified.  In  fact,  even 
these  extremes  are  exceeded  sometimes.  These  discrepancies  are  due 
in  part  to  differences  in  the  rate  of  development,  and  in  part  to  our 
inability  of  exactly  determining  the  time  of  the  fertilization  of  the 
ovum.  Evidently,  this  calculation  cannot  be  based  upon  the  day 
of  the  coitus,  because  fertilization  takes  place  at  variable  intervals 
after  insemination.  Such  differences  have  also  been  noted  among  the 
domestic  animals  in  which  the  duration  of  pregnancy  is  usually  deter- 
mined in  accordance  with  a  single  coitus.  In  the  cow,  for  example, 
it  is  estimated  at  280  days,  with  extremes  of  240  and  310  days,  and 
in  the  mare  at  36G  days,  with  extremes  of  307  and  412  days. 

Labor  consists  essentially  in  the  development  of  a  driving  force 
which  is  capable  of  separating  the  fully  formed  fetus  from  the  mother 
without  injury  to  either  participant.  Particularly  at  this  time  the 
female  genitals  display  their  dynamic  qualities  most  advantageously, 
and  this  is  true  especially  of  the  uterine  musculature  which  plays  the 
principal  part  in  this  process.  Already  during  pregnancy  the  woman 
experiences  intermittent  contractions  of  this  organ  which,  however, 
do  not  give  rise  to  unpleasant  sensations.  At  the  time  of  labor,  these 
contractions  increase  in  intensity  and  are  associated  with  a  distinct 
pain  which  possesses  a  peculiar  bearing  down  character,  i.e.,  they 
begin  in  the  sacral  region  and  slowly  pass  to  the  abdomen  and  to- 
ward the  thighs.  To  begin  with,  they  recur  at  intervals  of  from  15 
to  30  minutes,  but  later  on  as  frequently  as  every  2  minutes. 
They  may  then  last  for  60  to  90  seconds.  The  dilatation  of  the  cervix 
having  been  accomplished,  the  climax  of  these  "labor  pains"  is  reached 
at  the  time  when  the  head  distends  the  vulva.     In  many  cases,  how- 


THE    DEVELOPMENT    OF    THE    EMBRYO  1145 

ever,   the   suffciiiif:;   is   very   slight   and    Uihoi-   is   completed   almost 
without  pain. 

Those  contractions  possess  a  peristaltic  character  and  may  develop 
a  pressure  of  30  pounds,  the  average  being  17  pounds;  in  fact,  in  rare 
instances  pressures  of  from  50  to  100  pounds  have  been  encountered. 
It  should  not  be  forgotten,  however,  that  the  actual  expulsion  of  the 
fetus  also  brings  into  play  the  abdominal  press  which  greatly 
augments  the  force  of  the  uterine  musculature.  In  addition,  the  pa- 
tient braces  her  body  and  contracts  other  muscles  to  steady  herself. 
The  frequency  of  the  heart  and  the  arterial  pressure  increase  during 
the  contractions,  whereas  the  respiratory  rate  decreases.  The  process 
of  labor  is  usually  divided  into  three  stages,  namely: 

(a)  From  the  beginjiing  of  the  first  craiup-Hkc  pains  to  the  compU^tion  of  the 
dilatation  of  the  cervix;  leading  to  the  rupture  of  a  few  local  blood-vessels  and  the 
discharge  of  the  amniotic  fluid. 

(b)  From  the  rupture  of  the  membranes  to  the  complete  delivery  of  the  child. 

(c)  The  placenta  separates  from  the  uterine  wall  and  is  expelled  together  with  a 
small  quantity  of  blood  (500  c.c).  The  uterus  gradually  recedes,  forming  a  solid 
tumor  well  below  the  umbilicus. 

The  average  duration  of  labor  in  primiparse  in  18  hours;  16  hours 
of  this  period  being  consumed  by  the  first,  1  hour  and  45  minutes  by 
the  second,  and  15  minutes  by  the  third  stage.  It  is  usually  more  pro- 
longed in  elderly  women,  but  is  much  shorter  in  multiparse.  Labour 
is  essentially  a  reflex  process  in  which  the  uterine  musculature  plays 
the  principal  part.  The  correctness  of  this  deduction  is  proved  by 
the  fact  that  even  a  uterus  the  nerves  of  which  have  been  divided,  is 
capable  of  successfully  expelling  its  contents.  Consequently,  we  may 
omit  many  of  the  theories  which  have  been  formulated  to  explain  the 
onset  of  labor  and  confine  ourselves  to  those  which  hold  that  this 
process  is  not  dependent  upon  a  stimulation  of  certain  nerve  centers, 
but  is  instigated  by  a  local  stimulus  either  in  the  form  of  mechanical 
impacts  or  in  the  form  of  a  hormone  contained  in  the  blood  stream.  In 
the  first  instance,  the  presumption  would  be  that  the  steadily  growing 
fetus  eventually  produces  a  maximal  distention  of  the  uterus  and 
thereby  incites  a  contraction  of  its  musculature.  But  this  view  does 
not  coincide  with  the  observation  that  large  fetuses  are  often  retained 
for  a  much  longer  time  than  those  of  smaller  size.  Among  the  chemical 
theories  might  be  mentioned  the  one  advocated  by  Brown-Sequard 
(1853),  which  states  that  the  contractions  of  the  uterus  are  incited  by  a 
sudden  increase  in  the  carbon  dioxid  content  of  the  mother's  blood. 
This  explanation,  however,  does  not  clearly  depict  the  cause  of  this 
accumulation,  nor  is  it  quite  certain  that  ordinary  amounts  of  carbon 
dioxid  could  actually  produce  this  result.  More  plausible  are  those 
theories  which  localize  the  stimulus  in  the  fetus  itself.  Thus,  Spiegel- 
berg  has  stated  that  certain  of  its  excretory  substances  eventually  fail 
to  be  eliminated  and  attack  the  uterus  directly.     This  view  finds 


1146  THE  REPRODUCTR'E  ORGANS 

substantiation  in  the  experiments  of  Kruiger  and  Offergeld/  which 
prove  that  even  the  denervatcd  uterus  may  show  a  normal  onset  of 
labor.  In  addition,  Sauerbruck  and  Heide^  have  demonstrated  that 
artificially  united  female  rats  (symbiosis)  may  influence  one  another. 
Thus,  it  was  noted  that  the  onset  of  the  uterine  contractions  in  one 
invariably  produced  these  contractions  in  the  other  animal.  If, 
however,  the  other  was  not  pregnant,  it  then  showed  certain  symptoms 
indicative  of  a  serious  illness.  Eden^  and  Williams'*  have  called  atten- 
tion to  the  fact  that  the  placenta  undergoes  senile  changes  at  term 
which  increasingly  interfere  with  the  nutrition  of  the  fetus.  The 
accumulation  of  the  waste  products  resulting  in  consequence  of  this 
condition,  undoubtedly  evokes  local  stimuli  which  diminish  the  output 
of  nitrogen,  and  depress  the  general  processes  of  oxidation.  Conse- 
quently, we  are  forced  to  conclude  that  labour  is  under  the  direct  control 
of  a  local  mechanism  which  may  be  activated  either  chemically  or  me- 
chanically. The  central  nervous  system,  on  the  other  hand,  serves 
merely  as  a  regulating  and  correlating  agent.  It  is  a  well-known  fact 
that  emotions  and  other  sensor}^  impressions  maj^  influence  the  onset 
and  progress  of  labor  as  decidedly  as  the  activated  uterus  may  alter 
the  functional  state  of  other  organs. 

1  Archiv  fiir  Gynec,  Ixxxiii,  1907,  257. 

2  Miinchener  med.,  Wocheaschr.,  1910. 

3  Jour,  of  Path,  and  Bact.,  1897. 
*  Jour,  of  Obst.,  xli,  1910. 


INDEX 


Abdomixai.  press,  479,  531 
in  labor,  1145 
in  niict.urit.ion,  1077 
in  vomiting,  1011 

reflex,  598 

type  of  respiration,  466 
Abducens  nerve,  650 
Aberration,  chromatic,  815 

spherical,  815 
Ablation  of  cerebellum,  711 

of  motor  area,  effects  of,  679 
Absorption  bands  of  spectrum,   192 

from  cavities  of  body,  1033 

from  intestinal  canal,  1027 

of  carbohvdrates,  1029 

of  fats,  1030 

mechanistic  theory,  1031 
chemical  theory,  i031 

of  proteins,  1031 

of  water,  1027 

through  skin,  1034 
Acapnia,  521,  523 
Acceleration,  heart,  309 
Accelerator  nerve  fibers  of  heart,  311 
Accessory  nerve,  655 
Accommodation    in    various     animal^ 
820 

of  human  eye,  822 

normal,  limit  of,  828 
proofs,  823 
range,  828 

reflex,  648,  812,  814 
Acetone  in  urine,  1086 
Achilhs  jerk,  599 
Achlorhydria,  923 
Achromatic  lenses,  Dolland's,  816 
Achromatism,  816 
Achromatopsia,  888 
Achroo-dextrin,  993 
Acid,  cholalic,  947 

chohc,  947 

glycocholic,  947 

hematin,  spectrum  of,  195 

hippuric,  in  urine,  1087 

hydrochloric,  952 
•  sarcolactic,  1041 

taurocholic,  947 
Acidophiles,  199 
Acidosis,  1043,  1086 
Acini  of  glands,  892 
Acromegaly,  979 
Action,  reflex,  109 
Activator,  990 
Active  immunity,  246 
Acuitv,  tactile,  736 

visual,  838 


Adaptation  of  sense  organs,  732 
Addison's  disease,  969 
Adenoid,  907 

Adiadochokinesis  from  cerebellar    dis- 
ease, 713 
Adrenal  glands,  967 
function,  970 
innervation,  973 
position,  967 
removal,  9^9 
structure,  967 
Adrenalin,  952,  971 

effect  on  circulation,  971 
on  eye,  975 
on  metabolism,  975 
on  muscle  tissue,  975 
on  salivarj'  secretion,  916 
Adrenalin-glycosuria,  975 
Adrenalin-hyperglycemia,  975 
Adrenin,  971 

effects  on  circulation,  971 
Absorption,  1027 
Aerobes,  445 
Aerotonometer,  490 

Bohr's,  491 
Afferent  nerve  fibers  of  heart,   324 

neuron,  109 
After-birth,  1141 
After-images,  negative,  882 

positive,  882 
Age,  effect  of,  on  arterial  blood    pres- 
sure, 370 
on  metabolisin,  1054 
on  respiratory  quotient,  516 
Agglutinins,  248 
Agnosia,  auditorv,  697 
tactile,  684,  697 
visual,  697 
Agraphia,  690,  695,  696,  698 
Air  calorimeter,  1090 
complemental,  480 
composition  of,  effect  on  respiratory 

quotient,  516 
expired,  character  of,  486 
inspired,  character  of,  486 
minimal,  481 
residual,  480 
respired,  quantitative  determination, 

479 
stationary,  481 
supplemental,  480 
tidal,  480 

and   blood,    interchange   of    gases 
between,  488 
chemical  theory,  488,  494 
physical  theory,  489 


1147 


1148 


INDEX 


Air-bladder  of  fish,  450 

Air-cells  of  lung,  451 

Albuminuria,  1074 

Alcohol,  ei^ect  of,  on  speed  of  nerve  con- 
duction, 133 

Alcoholic  fermentation  of  milk,  901 
stimulants,  1063 

Alexia,  696 

Alexin,  250 

Alimentary    canal,    absorption    of    re- 
duced foodstuffs  from,  1022 
lengith  of,  in  various  animals,  999 
muscles  of,  1000 
of  birds,  998 
of  mammals,  998 
glvcosuria,  966,  1043 

Alteration  theory  of  electrical  current  of 
injury,  104 

Alternating;  reflexes,  592 

Altman's  theory  of  structure  of  proto- 
plasm, 24 

Alveolar  theory  of  structure  of  proto- 
plasm, 24 

Alveoli,  452 
of  lungs,  451 

Amaurosis,  887 

Amblyopia,  887 

Amboceptor,  251 

Ambrosial  odors,  747 

Ameboid  movement,  38 

Ametropia,  855 

Amino-acids  in  urine,  1087 

Amino-nitrogen,  1051 

Amitosis,  1109,  1110 

Ammonia,  1051 
in  urine,  1086 

Amnion,  1140 

Amniotic  fluid,  1140 

Amoeba,  20 

Amphibian  heart,  256 
lung,  451 

Ampulla,  hair-cells  of,  activation  of,  791 

Amusia,  698 

Amylase,  513,  935 

Amylolytic  action  of   pancreatic  juice, 
996 
enzvmes,  989 

Amylbpsin,  935,  996 

Anabolism,  985 

Anacrotic  limb  of  arterial  pulse,  383 

Anaerobes,  445 

Anaphase  of  mitosis  of  cell,  1111 

Anaphylactin,  252 

Anaphylaxis,  251 
to  apomorphin,  252 
to  cocain,  252 

Anarthria,  695 

Anelectrotonus,  143,  145 

Anemia,  pernicious,  905 
theory  of  sleep,  723 

Anencephalus,  671 

Anesthesia,  constriction  of  pupil  in,  814 

Anesthetics,  effect  of,  on  speed  of  nerve 
conduction,  133 

Anestrum,  1133 


Angiometer,  Hiirthlc,  383 
Animal  electricity,  99 

heat,  1089 

reflex,  584 
Animalculists,  1117 
Animals,  anosmatic,  690 

arterial  blood-pressure  in,  364 

circulatory  system  in,  254 

homoiothermal,  1093 

macrosmatic,  690 

microsmatic,  690 

osmatic,  690 

poikilothermal,  1093 

process  of  accommodation  in,  820 
Animate  material,  19 
.\nkle-clonus,  75,  592 
Annuli  fibrosi,  264 
Anode,  58 

Anosmatic  animals,  690 
Anoxemia,  521 
Antagonistic  reflexes,  592 
Anterolateral  tract,  superficial,  618 
Antibodies,  247 
Anti-enzyme,  992 
Antigens,  247 
Antiperistaltic  wave,  1014 
Antithrombin,  214 
Antitoxic  sera,  246 
Antitoxin,  diphtheria,  246 
Antrum,  mastoid,  764 

pylori,  1006 
Anvil  bone  of  ear,  766 
Aorta,  254 
Aortic  vestibule,  267 
Apex  beat,  location,  282 
Aphakia,  830 
Aphasia,  693 

motor,  694 

sensory,  696 
Aphemia,  695 
Apnea,  522 

fetalis,  523 

spuria,  523 

vagi,  523 

vera,  523 
Apomorphin,  anaphylaxis  to,  252 
Apoplexy,  230 
Appetite,  752 
Appetizers,  effect  of,  on  gastric  juice, 

930 
Apraxia,  695 
Aqueous  humor,  809 
Arachnoid,  716 
Arbor  vitse,  707 
Archipallium,  665 
Area,  body-sense,  681 

frontal  association,  699 

motor,  of  cerebrum,  671 
location,  673 
Areas,  touch,  739 
Argyll- Robertson  sign,  813 
Aristotle's  four  mundane  elements,  794 
Aromatic  odors,  747 
Arterial  blood  pressure.     See  Blood  pres- 
sure, arterial. 


INDEX 


1149 


Arterial  pulse,  377 
cause,  377 
frequency,  379 
percussion-wave,  384 
registration  of,  381 
wave,  anacrotic  limb,  383 
apex.  384 

catacrotic  limb,  384 
character,  383 
dicrotic,  384 
notch.  384 
postilicrotic,  384 
predicrotic,  384 
Arteries,  254 
Arterioles,  254 
Artery,  umbilical,  260 
Articulation,  positions  of,  55 
Artificial  respiration,  482.     See  Respira- 
tion, artificial. 
Aryepiglottic  folds,  544 
Arytenoid  cartilages,  542 

muscle,  547 
.\sphyxia.  525 

color  of  blood  in,  161 
Assimilation  leukocytosis,  201 

phenomenon  of,  31 
Association  area,  frontal,  699 
reflexes,  582,  592 
system  of  cerebrum,  661 
\'isual,  686 
Astasia  from  cerebellar  disease,  713 
Astereognosis,  684 

Asthenia  from  cerebellar  disease,  713 
Astigmatism,  855 
against  the  rule,  856 
irregular,  856 
regular,  856 
with  the  rule,  856 
Asynergia  from  cerebellar  disease,  712 
Ataxia  from  cerebellar  disease,  713 
Atmosphere,  446 

Atonia  from  cerebellar  disease,  713 
Atropin,  effect  of,  on  inhibitor  reaction 
of  heart.  317 
on  salivary  secretion,  916 
Aubert    and    Forster's    perimeter,    851 
Auditorv  agnosia,  697 
center,  689 
fatigue,  780 
meatus,  763 

external,  764 
nerve.  651 
radiation,  661 
Auricle,  auditory,  763 
Auricles  of  heart.  255 

discharging  period,  307 

filling,  in  intra-auricular  pressure, 

299 
function,  297 
longitudinal  layer,  265 
musculature  of,  265 
structure,  263 
transverse  layer,  265 
Auricular    complex    of    electrocardio- 
gram, 288 


Auricular  fibrillation,  279 

systole,   j)osition  of  heart  valves  in, 
■  307 

Auriculoventricular  bundle,  264 
valves,  268 

Auscultation  method  of  recording  arter- 
ial blood  pressure,  368 

Autacoid  substances,  952 

Autonomic  nervous  system,  627.     See 
Nervous  syste7n,  autonomic. 

Avalanche  conduction,  769 

Axis-cylinder,  111,  113 
function.  116 

Axon,  108,  111 

Axon-reflexes,  637 

B.\BiNSKi  phenomenon,  599 
Bacteria,    intestinal,    reaction    of,    on 
carbohvdrates,  997 
on  fats.  997 
on  proteins,  998 
Bacteriolysins,  248 
Bacteriolysis,  248 
Bahnung,  573 

Banting's  cure  for  obesity,  1056 
Barcroft's  blood-gas  apparatus,  501 
modification    of    Topler's    pump   for 
extraction  of  gases  from  blood,  499 
Barometric   pressure   of  gases,  changes 

in.  519 
Bart.holin's  duct,  909 

glands,  1136 
Basal  ganglia,  703 
heat  production,  1104 
membrane,  775 
Basedow's  disease,  959 
Basilar  membrane,  772 
Basket  cells,  707 
Basophiles,  199 
Bathmotropic     cardiomotor     impulses, 

315 
Baths,  effect  of,  on  bodv  temperature, 

1098 
Bell-Magendie  law,  620 
Bends,  522 
Beri-beri,  cause,  927 
Bernstein's  experiment  on  heart  beat, 

334 
Bert's  experiment  proving  centripetal 

nerve  conduction,  128 
Betz,  cells  of,  613 
Biconcave  lens,  800 

refraction  by,  803 
Biconvex  lens,  conjugate  foci,  801 
optical  center,  800 
principal  axis,  800 

focal  distance,  801 
refraction  by,  800 
secondary  axis,  800 
Bidder's  ganglion,  318,  332 
Bile,  938,  939 

characteristics,  940 
circulation,  947 
formation,  943 
function,  996 


1150 


INDEX 


Bile,  phospholipins,  948 
pigiueiits,  948 
resorption,  944 
special  constituents,  947 
storage,  941 
Bilicyanin,  blue,  948 
Bilirubin,  948 
Biliverdin,  948 
Bimolecular  reaction,  992 
Binocular  vision,  869,  872 
Biot's  respiration,  524 
Biplegia,  679 

Birds,  alimentary  canal  of,  998 
heart  of,  258 
lungs  of,  451 
Bismuth  x-raj^  study  of  stomach,  1008 
Bladder,  urinary,  1076, 

nervous  control,  1077 
Blastula,  1119 
Blepharospasm,  592 
Blmd  spot,  834 

demonstration  of,  835 
form  of,  836 
BUndness,  blue-,  888 
color-,  887 
green,  888 
psychic,  688 
red-,  888 
word-,  688,  696 
Block,  heart-,  278 
Blood,  157 

absorption  of  gases  by,  497 
and   tidal   air,    interchange    of  gases 
between,  488 
chemical  theory,  494 
physical  theory,  489 
and  tissues,  interchange  of  gases  be- 
tween, 496 
as  protective  mechanism,  245 
carbon  dioxid  in,  condition  of,  505 
chemical  composition,  168 
cholesterin  in,  169 
circulating,  total  quantity,  357 
circulation    of,    253,    347.     See    also 

Circulation. 
coagulation  of,  211.     See  also  Coagu- 
lation of  blood. 
color,  160 

corpuscles,  blood  plasma  and,  relative 
amount,  159 
determining    amount,    direct 
method,  159 
indirect  method,  160 
red,  172 

chemical  properties,  181 
color,  172 
composition,  181 
disintegration  of,  198 
duration  of  life,  197 
hemoglobin  and  stroma  of,  sepa- 
ration, 181 
increase   at  high  altitudes,    179 
Life  historj%  195 
number,  176 
physical  characteristics,  172 


Blood  corpuscles,  red,  shadows,  181 
shape,  172 
size,  174 

stroma  of,  constituents,  183 
variations  in  number,  178 
in  shape,  175 
white,  199 

allied  functions,  207 
chemical  composition,  201 
classifications,  199 
color,  199 
contractility,  202 
dualistic  origin,  202 
fate,  202 

formation  of,  in  spleen,  904 
monophyletic  origin,  202 
motion,  202 
number,  200 
origin,  202 

physical  properties,  199 
shape,  199 
size,  199 
decalcification  of,  effect  on   coagula- 
tion, 223 
defibrination,  226 
description,  159 
distribution,  226,  228 
dog's,  composition,  168 
dust,  159 

electrical  conductivity,  165 
extraction  of  gases  from,  497 
flow,  394 
friction  of,  166 
gaseous  composition,  522 
general  characteristics,  157 
greater  circuit,  259 
horse's,  composition,  168 
in  asphyxia,  161 
infusion  of,  230 
laked,  181 
lecithin  in,  169 
loss  of,  226,  230 
menstrual,  coagulability  of,  226 
methods  of  collecting,  221 

of  determining  quantity  of,  226 
nitrogen  in,  condition  of,  507 
odor,  162 

osmotic  pressure,  164 
oxygen  in,  condition  of,  502 
plasma,  159 

and    corpuscles,    relative   amount, 

159 
constituents,  170 
salted,  223 
plasma-poor,  180 
platelets,  159,  207,  208,  214 
fate,  208 

methods  of  examination,  208 
origin,  208 

physical  characteristics,  207 
policemen,  204 
pressure,  354 

arterial,    auscultation    method    of 
recording,  368 
cardiac  variations,  377 


INDEX 


1151 


Blood  pressure,  arterial,    effect  of  age 
on,  370 
of  change  of  position  on,  372 
of  deep  breathing  on,  371 
of  eating  on,  371 
of  lal)or  on,  371 
of  menstruation  on,  371 
of  nmscular  exercise  on,  371 
of  pregnancy  on,  371 
of  sleep  on,  370 
factors  influencing,  370 
graphic  method  of  recording,  368 
in  animals,  364 
in  various  arteries,  364,  366 
methods  of  determining,  362 
recording,    Crampton's  index  of 
conditions  in,  372 
direct" method,  362 
indirect  method,  362,  366 
palpation  method,  366 
variations  in,  365 
causes,  391 
pulsatory,  377 
respiratory,  390,  486 
capillary,  376 
venous,  373 

indirect  method  of  recording,  374 
negative,  area  of,  374 
variations  in,  cardiac,  388 
respiratory,  390 
causes,  391 
reactions  of.  164,  248 
residual,  229 
serum,  171,  212 
sodium  chlorid  in,  169 
specific  gravitv,  162 
velocity,  402 

determination  of,  404 
chemical  method,  397 
direct  method,  394 
indirect  method,  397 
stream,  volume,  394 

measuring    of,    calori metric 
method,  397 
sugar  content,  169 

supply,   cerebral,   regulation  of,   443 
taste,  162 
temperature,  162 
total  quantity,  226 
transfusion  of,  230 
urea  content,  170 
viscosity  of,  166 
whole,  composition,  167 
Blood-vessels,  elasticity  of,  358 
innervation  of,  411 
nervous  regulation  of,  411 
Blue-blindness,  888 
Bodies,  opaque,  795 
purin,  1051 
tigroid,  563,  564 
translucent,  795 
Body  cavities,  absorption  from,  1033 
ciliary,  819 

different    regions,     temperature    of, 
1094 


Body  fat,  source  of,  1044 
history  of  foodstuffs  in,  1037 
metabolic  requirements,  1052 
proteins,  source  of,  1048 
sugar  supply  of,  regulation,  1042 
temperature,  1093 

effect  of  baths  on,  1098 
of  clothes  on,  1101 
of  nervous  depressants  on,  1106 
of  varnishing  skin  on,  1105 
factors  varying,  1095 
in  various  regions,  1094 
regulation  of,  1097 
rise  of,  after  death,  1105 
voluntary  factors  controlling,  1101 
Body-sense  area,  681 
localization,  681 
Bohr's  aerotonometcr,  491 
Bolometer,  resistance,  1099 
Bolus,  food,  1001 
Bone-marrow,  myeloplaxes,  207 
Bones,    cranial,    conduction    of    sound 
waves  bv,  779 
ear,  764,  766 
movements,  767 
Bornstein's  chemical  method  of  meas- 
uring volume  of  blood  stream,  401 
Botulism,  1035 
Boyle's  law,  1025 
Brain,  growth,  717 

human,  convolutions  of,  667 
weight  of,  666,  718 
Brain-sand,  981 

Breasts.     See  Mammary  glands. 
Breathing,  deep,  effect  on  arterial  blood 

pressure,  371 
Brewster's  stereoscope,  876 
Brightness,  880 
Brodie  recorder,  399 
Brodie   and   Russell's  method  of  esti- 
mating coagulation  time  of  blood,  219 
Bronchi,  451,  452 
Bronchial  capacity,  481 

murmur,  477 
Broncliiolar  tubules,  451 
Bronchioles,  451,  452 
Brownian  molecular  motion,  37 
Brown-Sequard's  inhibition  theory   of 

sleep,  723 
Bruit  de  souffle,  368 
Buds,  lateral,  108 
Buffy  coat,  212 
Bulb,  olfactory,  644 
Bulbocavernosus  muscle,  1127 

reflex,  599 
Bulbospiral  fibers  of  ventricles,  266 
Bundle,  anterior  ground,  613 
tectospinal,  616 
Held's,  616 
lateral  ground,  613 
Lissauer's.  616 
Monakow's,  616 
of  Helweg,  616 
of  His,  264 
septomarginal,  616 


1152 


INDEX 


Burdach,  column  of,  613 

Burning  odors,  747 

Burtou-Opitzs  apparatus  for  measuring 
volume  of  blood  stream.  395 

Bush-tea,  1063 

Biitschli's  theory  of  structure  of  proto- 
plasm, 24 

Butter,  900 

Butyrin  of  milk,  902 

Cachexia  thyreopriva,  957,  962 
Caffeine,  1062 
Caisson  disease,  522 
Calcium  rigor,  337 

Calliano's  method  of  artificial  respira- 
tion, 483 
Calorie,  1091 
Calorimeter,  1090 
air,  1090 

micro-,  of  Hill,  1092 
respiration,  1091 
water,  1090 
Calorimetric     method     of     measuring 

volume  of  blood  stream,  397 
Calorimetry,  1089 
Canal,  membranous,  of  cochlea,  775 
of  Schlemm,  805 
osseous,  of  cochlea,  772 
Canahculus  lacrymalis,  808 
Canals,  semicircular,  771,  785 
Cannon     and     Mendenhall's     graphic 

coagulometer,  220 
Capillaries,  254 

contractilit}'  of,  416 
endotheliallining  cells  of,  207 
Capillary  blood  pressure,  376 

electrometer,  Lippmann's,  101 
Caproic  odors,  747 
Caproin  of  milk,  902 
Caprvlin  of  milk,  902 
Capsule  of  Tenon,  804,  869 
Capsules,     suprarenal,    967.     See    also 

Adrenal  glands. 
Caput  cornu  posterioris,  605 
Carbamid  in  urine,  1083 
Carbohydrate-fat,  1041 
Carbohydrates,  26 
absorption  of,  1029 
metabolisjn  of,  1038 
of  milk,  902 
of  muscle,  86 

reaction    of     intestinal  bacteria    on, 
997 
Carbon   dioxid,  effect  of,  on  speed  of 
nerve  conduction,  133 
in  blood,  condition  of,  505 
in  starvation,  1053 
production  of,  by  muscle,  88 
slight  increase  in  partial  pressure, 
effect    on    respiratory   quotient, 
518 
monoxid,  affinity  of  hemoglobin  for, 
187 
hemoglobin,  spectrum  of,   194 
Carbonates  in  urine,  1082 


Cardiac  muscle,  42 
tissue,  46 
recess  of  stomach,  1006 
Cardiogram,  284,  285 
Cardiograph,  284 
Cardiometer,  304 

Johannson  and  Tigerstedt,  304 
Roy's,  303 
Cardiomotor  fibers,  310 
Cardio-pneumatic  phenomenon,  1105 
Cardiosensory  fibers,  324 
Carnitin,  87 
Carnosin,  87 
Cartilages  of  larynx,  541 
Caruncula  lacrymalis,  808 
Caseinogen,  902 
Castration,  effect  of,  on  animals,  982 

on  human  beings,  983 
Catabolism,  985 
Cata  erotic  limb  of  arterial  pulse  wave, 

384 
Catalase,  513 
Catalysis,  987 
Cataract,  830 
Catelectrotonus,  143,  145 
Cathode,  58 
Caustics,  815 
CeUac  axis,  433 
Cells,  21 

basket,  707 

carbohydrates  of,  26 

central  or  chief,  of  gastric  glands,  920 

cerebrosids  of,  26 

chemical  energy,  32 

chemistry,  25 

cholesterin  of,  26 

constituents,  25 

cytochrome,  564 

cj'toplasm  of,  23 

Daniell,  57 
diagram,  57 

demilune,  909 

devouring,  204 

diagram,  25 

endothelial  fining  of  capillaries,  207 

energetics,  32 

fatty  acids  of,  26 

fiber,  of  Retzius,  786 

first,  origin  of,  20 

form,  22 

functional  relation  of  cytoplasm  and 
nucleus,  27 

germ,  1114 

giant,  207 

hair,  of  ear,  776,  777 

inorganic  substances  in,  26 

lipoids,  25 

mast-,  200 

mastoid,  764 

metabolism,  29,  30 

movement  by  changes  in  turgor,  37 
by  swelling  of  walls,  37 

neutral  fat,  26 

nuclein  of,  26 

nucleoproteids  of,  26,  29 


INDEX 


1153 


Cells,  nucleus,  24 
formation,  24 

of  Bctz.  613 

of  Deitcrs,  776 

of  Golgi,  607 

of  Levdig,  interstitial,  function,  984 

of  Purkinje.  560,  708 

olfactory,  power  of  reaction,  744,  745 

phosphatids  of,  25 

proteins  of,  26 

protoplasm  of,  21 

pseudonueleoli,  25 

pyramidal,  560 

size,  22 

somachrome,  564 

somatic,  1114 

sperm-,  1117 

stellate,  of  Kupffer,  939 

structure,  22 

water  of,  26 
Cell-division,  direct,  1109 

indirect,  1111 

simple,  1110 
Cell-globulin,  222 
Center,  111 

auditory,  689 

coughing,  641 

defecation,  reflex,  1019 

deglutition,  641 

diabetic.  1042 

for  closure  of  eyelids.  641 

for  secretion  of  saliva.  641 

geometrical,  of  spherical  mirror.  796 

glycogenic.  1042 

hearing.  689 

mastication,  641 

micturition,  reflex,  1077 

of  curvature  of  spherical  mirror.  796 

olfactorv,  644,  690 

sight.  684 

smell.  690 

sneezing.  641 

speech.  691,  693 

spinal,  for  ejaculations.  596 
for  erection,  596 

sucking.  641 

taste.  690,  691 

visual,  connection  with  other  centers, 
687 

vomiting,  641,  1012 
Centers,  heat-accelerator,  1102 

heat-inhibitory,  1102 

spinal  cord.  596 
Centrum  anospinale,  596 

vesicospinale.  596 
Cerebellar  localization.  713 

peduncle,  superior,  661 
Cerebellum,  706 

ablation  of,  711 

arbor  vita,  707 

as>'nergia  from  disease  of,  712 

connections,  709 

convolutions,  707 

function,  714 

inferior  vermis,  706 
73 


Cerebellum,  lobuli  complicati,  706 
lobulus  medianus  posterior,  706 

simplex,  706 
lobus  quadratus  anterior,  706 
median  iolx'  or  vermis,  706 
middle  peduncle  of,  709 
monticulus,  706 
moss  fil)ors  of,  708 
roof  ganglia  of,  708 
structure,  706 
sulcus  primarius,  706 
superior  peduncle,  709 

vermis,  706 
tendril  fibers  of,  708 
Cerebral   blood  supplv,   regulation   of, 
443 
circulation,  440 

cortex,    functional    separation,     671 
localization,  671,  681 
reflex  inhibition,  588 
Cerebrosides.  26 
Cerebrospinal  fluid,  236,  718 
function,  721 
system,  autonomic  system  and.  con- 
nections between,  631 
Cerebrum.  657 

anterior  commissure  of,  662 
association  system,  661 
commissural  system  of,  661 
comparative  physiology,  664 
general  function,  657 
grav  matter  of,  general  arrangement, 

657 
inherited  absence  of,  671 
mode  of  development.  662 
motor  area  of.  671,  673 
projection  system,  660 
removal  of,  668 
tracts  of,  classification,  659 
white   matter,   general  arrangement, 
658 
Cerumen,  764,  895 

Cervical  sympathetic  nerve,  vasomotor 
reaction  of,  422 
system,  631 
Chalones,  952 

Chauveau    unipolar    method  of  nerve 
and  muscle  stimulation, 
151 
effects  of,  154 
Chauveau    and  Lortet's  hemotachom- 

eter,  405 
Chemical  energy,  729 
imprint  theory  of  Ught  stimulation 

of  retina,  840 
rays,  880 
stimuli.  33 
theories  of  sleep,  723 
theory  of  fat  absorption,  1031 
of  secretion,  892 
Chemicals,  effect  of,  on  muscle  contrac- 
tion, 79 
Chemistry  of  muscle  fatigue,  89 
Chest  voice.  551 
Chest-register,  553 


1154 


INDEX 


Cheyne-Stokes  respiration,  523 

Chilarducci's  reaction  at  a  distance,  156 

Chloasmse,  1139 

Chlorhematin,  188 

Chlorids  in  urine,  1081 

Chlorocruorin,  160 

Cholagogues,  944 

Cholalic  acid,  947 

Cholemia,  944 

Cholesterin,  26 

in  blood,  169 

of  nerve,  114 
Cholesterol,  947 
Cholic  acid,  947 
Chorda  tvmpani,  912 
Chordae  tendinae,  267,  269 
Chorion,  1140 
Choroid,  806 

Chromatic  aberration,  815 
Chronometric  method  of  determining 

hemoglobin,  190 
Chronotropic     cardiomotor     impulses, 

315 
Churning,  haustral,  1019 
Chvle,  158,  234,  235 
Chyme,  1009 
Chvmosin,  925 
Cilia,  39 
Ciliary  body,  806,  819 

ligaments,  806 

movement,  39 

muscle,  806 

innervation  of,  830 
Cingulum,  661 
Circuit,  primary,  62 

secondary,  62 
Circular  fibers  of  ventricles,  267 
Circulating  blood,  total  quantity,  357 

protein,  1048 
Circulation,  253,  347 

action  of  epinephrin  on,  971 

analogous  features,  352 

cerebral,  440 

coronary,  427,  430 

effects  of  adrenalin  on,  971 
of  adrenin  on,  972 

Harvey's  discovery  of,  18 

mechanics,  347 

of  bile,  947 

peripheral  resistance  to,  361 

physical  consideration,  347 

portal,  433 

pulmonarv,  430 

renal,  433 

time  required  for,  409 

under  microscope,  408 
Circulatorv  svstem,  comparative  studv, 
253" 
coronary  circuit  of,  259 
development,  158 
during  fetal  life,  260,  261 
greater  circuit  of,  259 
lesser  circuit  of,  260 
of  fish,  256 
of  lower  animals,  254 


Circulatory  sj^stem  of  mammals,  258 
of  sponges,  254 
of  vermes,  255 
of  vertebrates,  255 
portal  circuit  of,  259 
pulmonary  circuit  of,  260 
systemic  circuit  of,  259 
Circumvallate  papillae  of  tongue,  748 
Clarke's  vesicular  column  of  cells,  607 
Clausius'  and  Schonbein's  ozone-auto- 
zone  theory  of  activation  of  oxvgen, 
511 
Cleavage  nucleus,  1119 
Clonic  contracture  of  muscle,  75 

reflexes,  592 
Clonus,  ankle,  592 
Clothes,  effect  of,  on  body  temperature, 

1101 
Clotting  of  blood,  211.     See  also  Coagv^ 

lation  of  blood. 
Coagulability  of  menstrual  blood,  226 
Coagulating  enzymes,  989 
Coagulation  of  blood,  211 

chemical  changes  in,  212 
conditions  influencing  time,  221 
effect  of  admixture  of  neutral  salts 
on,  223 
of  decalcification  on,  223 
of  hirudin  on,  225 
of  peptonization  on,  224 
of  snake  poisons  on,  225 
of  substances  derived  from  tis- 
sues on,  222 
of  temperature  on,  221 
extravascular,  211 
intravascular,  217 
physical  changes  in,  211 
time  required  for,  219 
of  milk,  901 
Coagulation-rigor  of  muscle,  93 
Coagulins,  222,  248 
Coagulometer  of  Cannon  and  Alenden- 

hall,  220 
Coagulum  of  blood,  211 
Coat,  buffy,  212 
Cocain,  anaphvlaxis  to,  252 
Cochlea,  771 

membranous  canal  of,  775 
osseous  canal  of,  772 
Ccelenterates,  circulatorv  svstem  of,  254 
Coffee,  1063 
Coil,  induction,  62 
Cola,  1063 

Cold  spots  of  skin,  742 
Collapse  of  lung,  457 
Colloid  goiter,  961 
Color  contrast,  882 
fusion,  880 
saturation  of,  880 
sensibility  of  retina,  884 
vision,  879 

Hering  theory  of,  886 
Ladd- Franklin  theory,  887 
theories  of,  885 
Young-Helmholtz  theory,  886 


INDEX 


1155 


Color-lilindnoss,  887 

Holmgren's  tests  for,  888 
Color-wliccl  of  Miixwell,  880 
Colors,  (•oiiiplciiicntary,  880 
Colostrum,  «>()() 

corpuscles,  898 
Column,  Tiirck's,  G12 

of  liunlMch,  ()13 

of  Flochsis,  613 

of  Gull,  013 
ColumiKP  carnp*,  207 
Comma  tract,  of  Schultzc,  016 
Commissural  system  of  cerebrum,  001 
Commissure,  anterior,  of  cerebrum,  662 

hippocampal,  002 
Commutator,  Fohl's,  61 
Compensation     method    of     detecting 

electric  variations  of  muscle,  102 
Compensatory  pause  in  heart  beat,  343 
Complement,  251 
Complemcntal  air,  480 
Complementary  colors,  880 
Complementophile,  251 
Complex  lung,  451 

reflexes,  592 
Compression-paralysis  of  nerve,    131 
Concavo-convex  lens,  800 
Conception,  1132 
Concha,  763 

Condiments  in  diet,  1062 
Conduction,  avalanche,  769 

nerve.     See  Nerve  conduction. 
Conductivity,  electrical,  of  blood,  165 

of  nerve,  124 

irritability  and,  differentiation,  124 

of  protoplasm,  35 
Cone-granules  of  retina,  832 
Conjugation,  1111 
Conjunctiva,  807 
Conjunctival  sac,  807 
Consonants,  sound  production  of,  554 
Constant  current,  62 
Consumption,  luxus,  1057 
Contractility  of  protoplasm,  35 
Contraction    of   muscle,   48.     See   also 
Muscle  contraction. 

of  degenerated   human   muscle   and 
nerve,  law  of,  155 

of  normal  human  nerve  and  muscle, 
law  of,  150 

period  of  muscular  movement,  43 

Pfliiger's  law  of,  146,  148,  149 

wave  of  muscle,  68 
Contracture  of  muscle,  74 
clonic,  75 
tonic,  75 
Contralateral  effects  of  hemisection  of 

spinal  cord,  626 
Conus  arteriosus,  256,  267 
Convolutions  of  cerebellum,  707 
Cooking,  proper,  value  of,  1061 
Coppie's  anemia  theory  of  sleep,  723 
Copulation,  1127 
Cord,  umbilical,  1142 
Cords,  vocal,  550 


Core-conductor,  Hermann's,  133 
Cornea,  805,  809 

anUirior  homogeneous  lamella  of,  H05 

post(u-ior  homogeneous  lamella  of,  805 

refractive  power,  809 
CornicuUe  laryngis,  542 
Coroiuiry  circuit  of  circulatory  system, 
259 

circulation,  427 
Corpora  Arantii,  272 

fibrosa  or  albicantia,  1131 

quadrigcmina,  704 
Corpus  callosum,  661,  701 

luteum,  1131 
false,  1131 
true,  1131 

striatum,  703 
Corpuscles,  colostrum,  898 

Golgi-Mazzoni,  734 

Krause's,  735,  736 

Malpighian,  904 

of  Grandry  and  Merkel,  735 

of  Herbst,"  735 

of  Meissner,  734 

pus-,  201 

red,  172.     See  also  Blood  corpuscles, 
red. 

salivary,  910 

white,  199.     See  also  Blood  corpuscles, 
white. 
Corpuscular  theory  of  light,  794 
Cortex,  cerebral,  functional  separation, 

671 
Cortical  function,  dynamic  theory,  701 
Corti's  organ,  activation,  777 
function,  777 
structure,  775 

rods,  776 

tunnel,  776 
Costal  type  of  respiration,  466 
Coughing,  482 

center  for,  641 
Cowper's  glands,  1126 
Crampton's  index  of  condition  in  re- 
cording blood  pressure,  372 

muscle,  822 
Cranial    bones,    conduction    of    sound 
waves  by,  779 

nerves,  640,  642 

functional  system  of,  642 

system,  631 
Cranioscopy,  Gall's  system  of,  672 
Cream,  900 
Creatin,  87,  1051 

in  urine,  1087 
Creatinin,  87,  1051 

in  urine,  1087 
Cremaster  muscle,  1123 
Cremasteric  reflex,  592,  598 
Crescents  of  Gianuzzi,  909 
Cretinism,  957 
Crico-arytenoid  muscle,  lateral,  547 

posterior,  547 
Cricoid  cartilage,  542 
Crista  acustica,  785 


1156 


INDEX 


Croaking  reflex  of  frog,  588 
Crusta  inflaiumatoria.  212 
Crying,  482 
Crypts  of  faucial  tonsils,  906 

of  Lieberkiihn,  908,  949 
Crystalline  lens,  820 

changes    in   shape    and    refractive 

power,  827 
wabbling  of,  826 
Crystals,  hemoglobin,  184 
Cuneiform  cartilages,  543 
Cuorin,  86 
Curd,  901 
Curvature   of   spherical  mirror,   center 

of,  796 
Cushny's    modern    theory    of    urinary 

secretion,  1072 
Cutaneous    receptors,     structure,     734 

secretions,  889 
Cuticle,  893 
Cutis  vera,  893 

Cybulski's  photo-hemotachometer,  405 
Cycle,  cardiac,  272 
Cytochrome  cells,  564 
Cj^ocvm,  215 
Cvtolvsins,  248 
Cvtolvsis,  248 
Cytophile,  251 
Cytoplasm,  23 

formed  elements,  23 

of  cell,  nucleus  and  functional  rela- 
tion, 27 

Dalton's  law  of  pressures,  497 

Daniell  cell,  57 

Dartos,  1123 

Darwin's  theory  of  evolution,  1121 

Deafness,  mind-,  688 

word-,  688,  689 
Deamination  of  ferments,  990 
Death,  reflex  cardiac,  326 

rise  of  body  temperature  after,  1105 
Decalcification  of  blood,  effect  of,  on 

coagulation,  223 
Decarboxylation  of  ferments,  990 
Decidua  basalis,  1140 

reflexa,  1140 

vera,  1140 
Defecation,  1019 

reflex  center  for,  1019 

spinal  center  for,  596 
Defibrination  of  blood,  226 
Deficiency  diseases,  927 
Degeneration,  fatty,  1047 

of  nerve,    117      See  Nerve  degenera- 
tion. 

Wallerian  law  of,  621 
Deglutition,  998,  1001 

center  for,  641 

function  of  esophagus  in,  1002 

mechanism  of,  1002 

nervous  control,  1004 
Deiters'  cells,  776 
Dehrium  cordis,  279 
Demilune  cells,  909 


Dendrites,  108,  560 
Dental  germ,  1001 
special,  1001 

sac,  1001 

sounds,  554 
Depression,  fatigue  of,  571 
Depressor  nerve,  325,  329 

vasomotor  reaction,  427 
Deprez-d'Arsonval    galvanometer.     99 
Dermis,  893 
Detention  theorv  of  accommodation  of 

eye,  822 
Deuterocerebron  of  crayfish,  580 
Deuteroplasm,  1130 
Diabetes  mellitus,  965 
Diabetic  center,  1042 
Dialvser,  1024 
Dialysis,  1024 
Diaminizing  enzymes,  989 
Diapedesis  of  leukocytes,  206 
Diaphragm,  454 

function  of,  in  respiratory  cycle,  462 
Diaphragmatic  type  of  respiration,  466 
Diaschisis  effect  of  Monakow,  701 
Diastase,  513 

Diastole  as  period  of  assimilation,  341 
Diastohc     pressure,    intracardiac,     296 
Diathesis,  exudative,  1051 
Diencephalon,  664 
Diet,   flavors  and  condiments  in,  1062 

inorganic  salts  in,  1061 

of  man,  normal,  1058 

stimulants  in,  1062 

value  of  proper  cooking,  1062 
Diffusion,  1023 

of  gases,  446 

of  proteins,  1026 

pressure,  446 
Digestion,  985 

chemistry  of,  985 

leukocytosis,  201 

mechanics  of,  998 
Digestive  secretions,  908,  918,  938 
Dilatation  of  heart,  345 
Dimethyl  xanthin,  1062 
Diphtheria  antitoxin,  246 
Diplopia,  873 

heteronymous,  872 

homonymous,  872 
Direct  blood  transfusion,  231 

vision,  837 
Disaccharides,  987 
Discrimination,  tactile,  625,  736 
Discus  proligerus,  1129 
Dismetry  from  cerebellar  disease,  713 
Dissimilation,  phenomena  of,  31 
Diuresis,  1073 
Diuretics,  1071 
Diver's  palsy,  522 
Dog  blood,  composition,  168 

talking.  692 
Dolland's  achromatic  lenses,  816 
Dromotropic  cardiomotor  impulses,  315 
Drugs,  action  of,  on  salivarv  secretion, 
916 


INDEX 


DruRs  constrictinR  pupil,  814 
diluting  pupil.  814 
effect  of,  on  iiiusclp  contraction,  79 
UuBois-RcvMumd's   experiment   in 
doiihle  nerve  conduction,  126 
induction  coil,  (52 
inductoriuni.  03 
key  for  nuikinR  and  hreakiny  current 

bO 
molecular  theory  of  electrical  current 
of  injury.  104 
Duct,  Bartholin's,  909 
pancreatic.  932 
of  Santorini,  932 
of  \\'irsunK,  932 
Ductless  glands,  889 
Ducts,  ejaculatory,  1126 
Ductus  arteriosus,  262 
choledochus,  941 
endolyinphaticus,  783 
pneuniaticus,  450 
venosus,  261 
Dudgeon's  sphygmograph,  382 
Duke  and   Howell's  theory  of  cardiac 

inhil)ition,  319 
Duodenal  juice,  931 
Dura  mater,  716 
Dust,  blood,  159 

Dynamic    phase   of   respiratory  cycle 
461  '        ' 

sense,  730,  785 

theories  of  reproduction,  1117 
theory  of  cortical  function,  701 
Dynamograph,  81.  82 
Dyschroinatopsia,  888 
Dysoxidizable  substances,  510 
Dyspnea,  471,  525 
heat,  475 

Ear,  anvil  bone  of,  766 

bones,  764,  766 
movements,  767 

external,  763 

hair  cells.  776,  777 

hammer-bone,  765 

inherent  muscles  of,  770 

internal,  771 

middle,  763,  764 

saccule,  771,  782 

stirrup  bone,  767 

utricle,  771,  782 
Eardrum,  764,  765 
Ear-wax,  895 
Echinochrome,  160 
Eck  fistula,  946 
Effectors,  different  types,  583 
Efferent  nerve  fibers  of  heart,  310 

neuron,  109 
Ehrlich's     side-chain     theory    of    im- 
munity, 249 

Einthoven's  string  galvanometer,  99,  286 
lijaculation  of  semen,  1 127 

spinal  center  for,  596 
Ejaculatory  ducts,  1126  j 

Elasticity  of  muscle,  65  I 


1157 


Electric  conductivity  of  blood,  165 
current,  axial,  in  nerve,  136 

constant    as(!ending,     reaction    of 
nerve  to,  142 
descending,  reaction  of  nerve  to 
142  ' 

reaction  of  normal  and  abnormal 
nerve  and  muscle  to,   142 
demarcation,  103 
external  resistance,  58 
in  muscles,  phases,  106 
internal  resistance,  58 
interrupted,  reaction  of  normal  and 
abnormal  nerve  and  muscle  to, 
142  ' 

making  and  breaking,  60 
measurement,  58 
of  action,  103 
in  nerve,  137 

wave  of  negativity  and,  relation 
.  ot  nerve  impulse  to,  138 
of  injury,  103 

alteration  theory  of,  104 
in  nerve,  135 
molecular  theory  of    104 
of  rest,  103 
types,  62 
stimulation  of  muscle,  57 
stimuli,  35 

theory  of  light  stimulation  of  retina, 
840  ' 

of  nerve  conduction,  133 

variations  of  heart,  286 
Electricity,  animal,  99 
Electrocardiogram,  287 

auricular  complex,  288 

ventricular  complex,  288 
Electrocardiograph,  287 
Electrocardiographv,  286 
E  ectrodes,  non-polarizable,  59 
Electrolvtes,  1025 
Electrometer,     capillary,     Lippmann's, 

Electromotive  force,  58 
Electronegative  oxygen,  510 
Electrotomc  condition  of  nerve,  method 
_  of  testing,  146 
differences  on  making  and  breakin<r 
galvanic  current,  144  ° 

Electrotonus,  142,  143 
extrapolar,  143 
intrapolar,  143 
physical.  143 
physiological,  143 
Embolus,  218 
Embryo,  development    1135 

nutrition  of,  1142 
Emission  of  semen,  spontaneous,  1128 

theory  of  light,  794 
Emmetropia,  855 
Emphysema,  457 
Encephalon,  716 
Endocardium,  263 
Endocrine  organs,  953 
Endo-enzyme,  988 


1158 


INDEX 


Endosonouc  protein,  1049 
Endolymph,  771 
Endoiicuriuiii,  111 
End-orsans  of  nerve-fiber,  1 13 
End-products   of   protein   metabolism, 

1050 
Energy,  chemical,  729 

different  manifestations  of,  727 

vibratory,  728 
Engelniaiin's  artificial  muscle,  49 

method  of  testing  electrotonic  condi- 
tion of  nerve,  145 

theory  of  muscle  contraction,  49 
Enterograph,  1013 
Enterokinase,  932,  935,  950,  997 
Entoptic  phenomena,  854 
Enzymes,  981 

muscle,  87 

of  pancreatic  juice,  935 
Eosinophilic  leukocytes,  200 
Ependyma,  663 
Epicardium,  263 
Epidermis,  893,  1123 
Epiglottis,  function,  543 
Epilepsy,  Jacksonian,  677 

traumatic,  677 
Epimysium,  43 

Epinephrin,  action  on  autonomic  nerv- 
ous system,  974 
action  on  circulation,  971 
Epineurium,  111,  970,  971 
Epiphysis  cerebri,  980 
Equilibrium,  nerve  of,  651 

nitrogen-,  1049 

sense  of,  781 
Erb's  reaction,  156 
Erectile  tissues,  male,  1126 
Erection  of  penis,  1127 

spinal  center  for,  596 
Erepsin,  932,  935,  950,  997 
Ergograph,  81,  82 

Ergotoxin,  effect  of,  on  salivarv  secre- 
tion, 916 
Erythroblasts,  196 

Erythrocytes,  172.     See  also  Blood  cor- 
puscles, red. 
Erythro-dextrin,  993 
Esophagus,  function  of,  in  deglutition, 

1002 
Esthesiometer,  735 
Estrus,  1133 
Ether,  794 

luminiferous,  794 
Ethereal  odors,  747 
Ethylene,  187 
Euglobulin,  172 
Euler  and  Huyghens'  undulatory  theory 

of  light,  794 
Eustachian  tube,  764,  769 

valve,  262 
Evolution,  Darwin's  theory  of,  1121 
Excised  heart,  331 
Excitation,  fatigue  of,  571 

of  muscle,  51 
Excretion,  1064 


Exercise,  muscular,  effect  of,  on  metab- 
olism, 1054 
Exo-enzyme,  988 
Exogenous  protein,  1049 
Expiration,  448,  461 
Expiratory  movement,  470 
Expired  air,  character  of,  486 
Explosive  sovmds,  554 
Extensibility  of  muscle,  65 
External  ear,  763 
Exteroceptors,  730 
Extractives  of  muscle,  87 
Extramural  circulatory  system,  428 
Extrasystole,  338 

cause,  341 
Extravascular     coagulation    of    blood, 

211 
Extrinsic  muscles  of  inspiration,  466 
Eye,  803 

anterior  chamber,  806 

constant  optical  defects,  853 

effect  of  adrenalin  on,  975 

electrical    variations    in,    on    visionj 
844 

functions,  804 

human,  accommodation  of,  822 
limit,  828 
proofs,  823,  824 
range,  828 

humors  of,  237 

optical  defects  of,  acquired,  855 
inconstant,  855 

posterior  chamber,  806 

protective  appendages,  803 

reduced,  846 

refraction  of,  abnormalities  in,  853 

refractive  power  of,  ophthalmoscopic 
test,  863 
shadow  test,  867 

schematic,  846 

suspensory  ligament,  821 

teeth,  1001 

visual  axes  of,  secondary,  837 
axis  of,  837 

white  of,  805 
Eyeball,  803 

anterior  cavity,  805 

general  structure,  803,  804 

measurements,  804 

minute  structure,  805 

movements  of,  869,  870 

posterior  cavity,  805 

sclera,  805 
Eyelids,  806 

closure  of,  center  for,  641 

Facial  muscles,  reflexes  from,  599 

nerve,  650 
Facilitation,  573 
Falsetto  voice,  551 
Falx  cerebri,  716 

cerebelH,  716 
Faradaic  current,  62 
Far-point  of  vision,  828 
Far-sightedness,  860 


INDEX 


1159 


Fasciculus  anterior  i>roprius,  G13 

autcrolaU'ralis  supcriiirialis,  ()13 

coirl)rosi)iiialis  autcrior,  012 
laU-ralis.  ()13 

cuuoatus,  ()13 

gracilis,  ()13 

lateralis  i)ruprius,  013 

loixKitudinal,  interior,  661 

longitudinal,  sujjerior,  661 

occipitofrontal,  061 

spinocerehellaris,  613 

uncinate,  001 
Fatiu;ue,  auditorj'-,  780 

ettect  of,  on  muscle  contraction,   80 

muscle,  chemistry  of,  89 
Treppe  phenomenon,  90 

nerve,  139,  140 

of  depression,  571 

of  excitation,  571 

of  nerve  cells,  568 
cause,  570 

of  sense-organs,  732 

reflex,  585 

substances,  90 
Fat,  body,  source  of,  1044 

carbohydrate-,  1041 
Fats,  absorption  of,  1030 
chemical  theory,  1031 
mechanistic  theory,  1031 

metabolism  of,  1044 

of  milk,  902 

reaction  of  intestinal  bacteria  on,  997 

utilization,  1046 
Fat-splitting  enzyme  of  saliva,  994 
Fatty  degeneration,  1047 
Faucial  tonsils,  crypts  of,  906 
function,  906 
removal  of,  effects,  907 
Feces,  character,  1035 

contents,  1035 

formation,  1035,  1036 
Fechner's  psychophysical  law,  733 
Fecundation",  1117 
Female  reproductive  organs,  1122 
Fenestra  ovalis,  764 

rotunda,  704 
Fermentation,  987 

of  milk,  alcoholic,  901 
Ferments,  987 

classification,  988 

deamination  of,  990 

decarboxylation  of,  990 

hydrolysis  by,  990 

intermediate  products  of,  991 

manner  of  action,  990 

nature  of,  988 

number  of  molecules  in  action  of,  991 

optimum  temperature  for,  991 

oxidation  of,  991 

reduction  of,  991 

respiratory,  513 

reversibility  of,  991 

self-inhibition  of,  962 
Fertilization,  1117 

of  ovum,  1118 


Fetal  life,  circulatory  svstem   in,   200, 

2()1 
Fetid  odors,  747 

Fetus,  oxvgen  requirement  of,  ]  142 
Fever,  high,  110(5 

Liebermeister'.s     neurogenic     theory, 
1107 

low,  1100 

toxogenic  theorv,  1107 
Fiber  cells  of  Rctzius,  780 
Fibers,  fili(>t  system  of,  061 

frontopontine,  601 

moss,  of  cerebellum,  708 

muscle,  43,  44 

intermediate  discs,  44 
transverse  discs,  441 

temporopontine,  661 

tenclril,  of  cerebellum,  708 
Fibril!;e,  44 

Fibrillar  hypothesis  of  nervous  system, 
565 

theory  of  structure   of    protoplasm, 
24 
Fibrillation,  auricular,  279 

of  heart  muscle,  279 

ventricular,  279 
Fibrin,  212,  217 
Fibrin-ferment,  171,  215 
Fibrinogen,  170,  171,  213,  216 

tissue-,  222 
Field,  visual,  851 
Figures,  Miiller-Lyer,  878 

Purkinje's,  839 
Filiform  papillae  of  tongue,  748 
Fillet,  median,  684 

system  of  fibers,  661 
Filtration  theory  of  formation  of  lymph 
238  i^   ' 

of    salivary    secretion,    facts    dis- 
proving, 917 
of  secretions,  892 
of  urinary  secretion,  1067 
Filum  terminale,  604 
Fish,  circulatory  system  of,  256 

swim-bladder  of,  450 
Fistula,  Eck,  946 
Flavors  in  diet,  1062 
Flechsig's  column,  613 

tract,  017 
Fleischl's  hemoglobinometer,  191 
Flesh,  goose,  894 
Fluoroscopic  examination  of  intestinal 

movements,  1013 
Focus,  virtual,  798 
Follicles,  Graafian,  1129 

hair,  893 

primordial,  1129 
Fontana,  spaces  of,  805 
Food,  986 

bolus,  1001 

effect  of,  on  arterial  blood  pressure, 
371 

nutritive  value,  1058 
Foodstuffs,  986 

history  of,  in  bodj-,  1037 


1160 


INDEX 


Foodstuffs,  reduced,  absorption  of ,  from 

alimentary  canal,  1022 
Foramen  ovale,  262 
Foramina  Thebesii,  264,  428 
Forebrain,  6G3,  664 
Fovea  centralis,  836 
Fragrant  odors,  747 
Frank's     instrument     for     registering 
heart-sounds,  290 

meml)rane  manometer,  297 
Fraunhofer  lines  of  spectrum,  193 
Friction  of  ])lood,  166 
Frog  preparation,  rheoscopic,  104,  105 
Frontal  association  area,  699 
Fninkel's  theory  of  menstruation,  1134 
Friction  sounds,  554 
Frog,  compound,  1116 
Frontopontine  fibers,  661 
Fundus    of    stomach,    movements   of, 

1005 
Fungiform  papilte  of  tongue,  748 
Funiculus,  anterior,  612 

lateral,  613 

posterior,  613 
Fusion  of  colors,  880 

Gad's  pneumatograph,  480 
Galactosids  of  nerve,  114 
Gall's  system  of  cranioscopy,  672 
Gall-bladder,  939 

innervation,  942 
Galvanic  current,  62.     See  also  Electric 

current,  constant. 
Galvanism,  99 
Galvanometer,  99 

string,  Einthoven's,  286 

for  measuring  speed  of  nerve  con- 
duction, 130 
Galvanotonus,  152 
Galvanotropic  reaction,  789 
Ganglia,  basal,  703 

roof,  of  cerebellum,  708 
Ganglion,  Bidder's,  318,  332 

in  peripheral  nervous  system.  111 
intervertebral,  619 
Remak's,  318,  332 
spirale,  777 
Garlic  odors,  747 

Gartner's  method  of  estimating  hemo- 
globin, 191 
Gases,  absorption  of,  by  blood,  497 
by  liquids,  496 
diffusion,  446 

extraction  of,  from  blood,  497 
interchange  of,   between  blood  and 
tissues,  496 
between  tidal  air  and  blood,  488 
chemical  theory,  494 
physical  theory,  489 
in  placenta,  451 
Gaskell's    trophic    theory    of    cardiac 

inhibition,  319 
Gastric  artery,  433 
cells,  central  or  chief  cell  of,  920 
'glands,  918 


Gastric  glands,  histological  changes  in 
secretion,  920 
of  cardiac  end,  919 
of  fundus,  919 
oxyntic  cells  of,  920 
parietal  cells,  920 
hunger,  754 
juice,  920 
acidity,  923 
antiseptic  action,  994 
artificial,  922 

effect  of  appetizers  on,  930 
function,  993 
hydrochloric  acid  of,  923 
inverting  action  of,  994 
methods  of  obtaining,  921 
origin  of  active  principles,  920 
psychic     element     in     formation, 

930 
secretion,  nervous  control,   928 

regulation  of,  926 
study  of,  by  psychic  feeding,  930 
by  sham  feeding,  930 
mucosa,  internal  secretion  of,  967 
secretin,  927 
secretions,  918 
Gastrin,  927,  931 
Gastro-enterostomy,  1010 
Gemmules,  lateral,  108 
Genital  organs,  female,  1122 
internal  secretions  of,  981 
male,  1122 
Geometrical  center  of  spherical  mirror, 

796 
Germ  cells,  1114 
dental,  1001 
special,  1001 
Germinal  spot,  1130 
Giant  cejls,  207 
Gianuzzi,  crescents  of,  909 
Gills,  448 

structure,  449 
Glan  and  Vierordt's  method  of  deter- 
mining hemoglobin,  190 
Gland,  pineal,  980 

pituitary,    977.     See    also    Pituitary 

gland. 
prostate,  1126 
thymus,  951,  963.     See  also  Thymus 

gland. 
thyroid,  951,  954.     See  also  Thyroid 
gland. 
Glande  interstitielle  I'ovaire,  982 
Glands,  acini  of,  892 

adrenal,      967.      See     also     Adrenal 

glands. 
Bartholin's,  1136 
Cowper's,  1126 
ductless,  889 
endocrine,  953 

gastric,  918.     See  also  Gastric  glands. 
intestinal,  948 
lacrimal,  807 

secretion,  807 
lobes  and  lobules,  892 


INDEX 


1161 


Glands,    mammarj',   897.      See    Mam- 
mary ylandn. 

meil)onuaii,  SO'.) 

mucous,  .siMTctorv  product,  907 

parathyroid,     9.51,     954.     See     also 
I'drathifroid  glaruls. 

racemose,  892 

salh-ary,     908.     Sec     also     Salivary 
glands. 

sebaceous,  894 

sexual,  982 

sweat-,  895 

tubular,  892 

tubulo-racemose,  892 

urethral,  1126 
Glans  penis,  1126 
Globin,  183 
Globulin,  cell-,  222 
Glossopharyngeal  nerves,  534,  653 

function,  749 
Glottis,  540,  543 
Gluteal  reflex,  598 
Glvcocholic  acid,  947 
Glycogen,  965,  1039 

disappearance  of,  in  muscle,  89 

formation  of,  1038 
Glycogenase,  513.  1039 
Glycogenesis,  1042 
Glycogenic  center,  1042 
Glvcogenolvsis,  1039,  1042 
Glycolysis,  "1042 
Glycosuria,  adrenalin-,  975 

alimentary,  1043 

conditions  causing,  966 

hepatic,  1043 

pancreatic,  1043 

phloridzin,  1043 

renal,  1043 
Goiter,  colloid,  961 

springs,  958 
Golgi's  cell,  607 
Golgi-Mazzoni  corpuscles,  734 
Goll,  column  of,  613 
Goose  flesh,  634,  894 
Gouty  diathesis,  1051 
Gower's  fluid,  177 

hemoglobinometer,  191 

tract,  613,  618 
Graafian  follicles,  1129 

mature,  1130 
Grandry   and    Merkel,    corpuscles    of, 

735 
Granula  theory  of   structure  of  proto- 
plasm, 24 
Granules, Nissl's,  108,  563,  564 

zymogen,  909 
Graphic  method  of  recording  arterial 

blood  pressure,  368 
Graves'  disease,  959 
Gray  matter,  cerebral,  general  arrange- 
ment, 657 
of  spinal  cord,  functional  basis,  606 
Green-blindness,  888 
Grehant   and  Quinquaud's  method  of 

determining  quantity  of  blood,  227 


Ground  bundle,  anterior,  (5 13 

lateral,  613 
Growth,  29,  1109 

factor  of,  in  metabolism,  1059 

movement  })y,  38 
Guanidin  metabolism  in  thyroid  gland, 

963 
Guanine,  1051 
Guarana,  1063 
Gustometry,  751 
Guttural  sounds,  554 

Hair,  893 

cells  of  ampulla,  activation  of,  791 

of  ear,  776,  777 
follicles,  893 
roots,  893 
Haldane  and  Smith's  method  of  esti- 
mating oxygen  tension  in 
arterial  blood,  492 
quantity  of  blood,  227 
Hammer-bone  of  ear,  765,  766 
Haptophore,  249 
Harmonies,  760 
Harmozones,  953 
Harvev's    discovery    of    circulation   of 

blood,  18 
Haustral  churning,  1019 
Hay  em's  fluid,  177 
Head-pressure,  350 
Hearing,  center,  689 
limits  of,  780 
nerve  of,  651 
sense  of,  756 
Heart,  1.58,  255 
acceleration,  309 
character,  323 
accelerator  nerve  fibers,  311 
action  current  of,  286 
afferent  nerve  fibers  of,  324 
beat,  compensatory  pause,  341 

effect    of    Ringer's    solution     on, 

336 
internal  stimulus,  nature  of,  336 
myogenic  theory,  334 
neurogenic  theory,  332 
origin,  331 
premature,  343 
refractory  period,  338,  341 
center,  309 

compensatory  hypertrophy,  343 
contraction,   character,   274 
wave,  path  of,  275 

speed  of,  275 
cycle  of,  272 
number,  272 
phenomena  in,  280 
time  relation  of,  305 
dilatation,  345 

effect  of  pressure  on  vagus  on,  327 
efferent  nerve  fibers,  310 
electrical  variations,  286 
excised,  331 
filling  of,  292 
first  sound,  290 


1162 


INDEX 


Heart,  form  of,  changes,  281 

methods  of  registering,  281 
hypertrophy,  345 
impulse,  282 
inhibition,  309 

cause,  318 

character,  312 

escape  of,  323 

Howell  and  Duke's  theory,  319 

nature  of,  315 

result,  320 

trophic  theory  of,  319 
inhibitor  nerve  fibers.  310 
measurements,  263 
mechanics  of,    253 
muscle,  fibrillation  of,  279 

physiological  properties,  338 

tissue,  functional  peculiarities,  331 

tonus  of,  344 
musculature  of,  arrangement,  263 
nervous  regulation,  309 
of  amphibians,  256 
of  birds,  258 
of  reptiles,  257 
output,  302 
reflex  death,  326 
second  sound,  289,  291 
secondary  augmentation,  314 
sounds,  289 

relationship  between,  291 
third  sound,  289,  292 
trigeminus  reflex,  327 
valves,  263 

arrangement,  267 
plan  of,  306 

position  of,  in  auricular  systole,  307 
in  ventricular  systole,  307 
variations  in  arterial  blood  pressure, 

377 
Heart-block,  278 
Heat,  dissipation  of,  1089,  1097 
dyspnea,  475 
in  animals,  1133 

of  bod}^,  1093.     See  also  Body  tem- 
perature. 
polypnea,  1095 
production,  1089,  1092,  1097 

basal,  1104 

ordinary,  1105 
sources,  1092 
spots  of  skin,  742 
total  quantity,  1103 
unit  of  measurement,  1090 
Heat-accelerator  centers,  1102 
Heat-inhibitory  centers,  1102 
Heat-rays,  880 
Heidenhain's     chemical     or     vitaUstic 

theory  of  secretion,  892 
classification  of  salivary  glands,  908 
theory  of  formation  of  lymph,  238 

of  urinary  secretion,  1068 
Held's  bundle,  616 
Helicotrema,  773 
Helmholtz's  detention  theory  of  acdom- 

modation  of  eye,  822 


Helmholtz's    method    of    determining 
speed  of  nerve  conduction,  129 

ophthalmometer,  858 

ophthalmoscope,  863 

phacoscope,  826 

resonator,  762 

resonance  theory  of  hearing,  777 
Helweg's  bundle,  616 
Hematin,  183,  188 

acid,  spectrum  of,  195 
Hematoblasts,  208 
Hematocrit,  159 
Hematoidin,  189 
Hematopoiesis,  197 

Hematopoietic  function  of  faucial  ton- 
sils, 906 
of  spleen,  905 

tissues,  196 
Hematoporphyrin,  189,  1080 

spectrum  of,  195 
Hemerythrin,  160 
Hemianopia,  bilateral,  685 
Hemianopsia,  685,  696 
Hemic  murmurs,  780 
Hemin,  188 

crystals,  188 
Hemiplegia,  679,  695 
Hemochromogen,  183,  188 

spectrum  of,  195 
Hemoconiae,  159 
Hemocyamin,  160 
Hemocytometer,  Thoma-Zeiss,  176 
Hemodromograph,  Chauveau  and  Lor- 

tet's,  405 
Hemodromometer,  Volkmann's,  404 
Hemodynamics,  347 
Hemoglobin,    affinity    of,    for    carbon 
monoxid,  187 

and  oxygen,  compounds  of,  proper- 
ties, 185 

and  stroma  of  red  corpuscles,  separa- 
tion, 181 

carbon  monoxid,  spectrum  of,  194 

compounds,  186 

constituents,  183 

crystals,  184 

derivative  compounds,  187 

spectroscopic  analysis,  192 

determination,  chronometric  method, 
190 
chnical  methods,  189 
estimation,  Tallquist's  method,  191 

nitric  oxid,  spectrum  of,  194 

reduced,  183 

spectrum  of,  193 

spectroscopic  analysis,"  192 
Hemoglobinometer,  Fleischl's,  191 

Gower's,  191 

Hoppe-Seyler 's,"  19 1 
Hemolysins,  181 
Hemolysis,  181,  248 
Hemometer,  191 
Hemophiha,  221 
Hemophotographic  method  of  estimate 

ing  hemoglobin,  191 


INDEX 


11G3 


Hemopyrrol,  189 
Heniorrhuf^i',  2;i() 
HeiiioUichometer,   Chauvcau  and  Lor- 

tet's,  4U5 
Henilerson's  cardiometer,  304 
Henle's  spliincter,  1128 

U-shapecl  loop,  1065 
Hepatic  artery,  433 

glycosuria,  960,  1043 

plexus,  939 
Herbst,  corpuscles  of,  735 
Hering's  method  of  estimating  circula- 
-tion  time,  409 

theory  of  color  vision,  886 
Hermann's  core-conductor,  133 

demarcation  current,  103 
Herpes  zoster,  622 
Heteronymous  diplopia,  872 
Heterophoria,  873 

Hibernating  animals,  respiratory  quo- 
tients in.  515 
Hiccough,  482 
High  fever,  1106 
Hill's  micro-calorimeter,  1092 
Hindbrain,  663,  664 
Hippocampal  commissure,  662 
Hippuric  acid  in  urine,  1087 
Hirudin,    effect   of,    on   coagidation   of 

blood,  225 
His's  bundle,  264 

theory  of  neuroblasts,  559 
Holmgren's  tests  for  color-blindness,  888 
Homoiothermal  animals,  1093 
Homolateral  effects  of  hemisection  of 

spinal  cord,  626 
Homonymous  diplopia,  872 
Hoppe-Sej-ler's  hemoglobinometer,  191 

indirect   method  of  determining 
amount  of  blood  corpuscles,  160 

theory  of  activation  of  oxygen,  512 
Hoppe-Seyler    and     Welker's    chrono- 

metric  method  of  determining  hemo- 
globin, 190 
Hormones,  926,  952,  953 
Horopter,  874 
Horse  blood,  composition,  168 

talking,  692 
Howell   and  Diike's  theory  of  cardiac 

inhibition,  319 
Humor,  aqueous,  809 

vitreous.  810 
Humors  of  eye,  237 
Hiirthle's    angiometer,    383 

apparatus  for  estimating  volume  of 
blood  stream,  395 

membrane  manometer,  296 
Hunger,  753 

gastric,  754 

sense,  743 

somatic,  754 
Hutchinson's  spirometer,  479 

Wintrich's  modification,  479 
Huyghens        and    Euler's    undulatorv 

theory  of  light,  794 
Hyaloplasm,  24 


Hydraulic  pressure,  347 
Hydremic  plethora,  1074 
Hydrobilirubiu,  948 
Hydrochloric  acid,  952 

of  gastric  juice,  923 
Hydrodynamic  pressure,  347 
Hydrolysis  of  ferments,  990 
Hydrolytic  oxidations,  511 
Hydrostatic  pressure,  347 
Hydrothorax,  457 
Hyperchlorhydria,  923 
Hypermetropia,  855,  860 
Hypermetry  in  cerebellar  disease,  713 
Hyperosmotic  solution,  1025 
Hyperpnea,  524 
Hyperpyrexia,  1106 
Hyperthermy,  1106 
Hyperthymusism,  964 
Hyperthyroidism,  957,  959 
Hypertonic  solution,  1025 
Hypertrophy  of  heart,  345 
Hypnotic  sleep,  724 
Hypogastric  arteries.  262 
Hypoglossal  nerve,  656 
Hypoleukocytosis,  201 
Hypophysin,  978 
Hypophy.sis     cerebri,     977.     See     also 

Pituitary  gland. 
Hyposmotic  solution,  1025 
H\'pothermy,  1106 
Hypotonic  solution,  1025 
Hypoxanthine.  1051 

Icterus,  944 
Ileocecal  valve,  1017 
Illusions,  optical,  876 

touch,  739 
Image,  real,  797 

retinal,  formation,  846,  848 

virtual,  798 
Images,  Purkinje's,  839 
Immune  body,  251 
Immunity,  245 

acquired,  246 

active,  246 

antibodies  in,  247 

causes,  247 

complete,  245 

Ehrlich's  side-chain  theory-,  249 

general,  246 

local,  246 

natural,  246 

nature  of  reactions  in,  248 

partial,  245 

passive,  246 

permanent,  246 

phagocytosis  in,  247 

temporary,  246 
Implantation  of  o\'Tim,  1137 
Impulsus  cordis,  282 
Inanimate  rnaterial,  19 
Incus,  766 
Index  of  refraction,  798 

opsonic,  206 
Indican  in  urine,  1082 


1164 


INDEX 


Indirect  blood  transfusion,  231 

vision,  S37 
Indol  in  urine,  1082 
Induced  current,  62 
Induction  coil.  62 

Inductorivmi,  DuBois-Reymond,  63 
Infantilism,  957 
Infundibula,  452 

Infundihulum  of  pituitary  gland,  977 
Infusion  of  blood.  230 
Inhibition,  heart,  309 
of  nerve  cell,  574 
of  reflexes,  588 
theorv  of  sleep,  723 
Inhibitor  nerve  fibers  of  heart,  310 
Innervation  of  adrenal  glands,  973 
of  ciliarv  muscle,  830 
of  gall-bladder,  942 
of  iris,  817 
of  larynx,  535,  547 
of  mammary  glands,  899 
of  salivary  glands,  911 
of  stomach  musculature,  1012 
of  sweat-glands,  897 
Inorganic  salts  in  diet.  1061 
Inotropic  cardiomotor  impulses,  315 
Insects,  respiration  in,  448 
Inspiration,  448,  461 

muscles  of,  466 
Inspiratory  movement,  466 
Inspired  air,  character  of.  486 
Insufflation,  constant^  ^486 
Intensity  of  sounds.  758 
Intercostal  muscles,   action  of,   m  res- 
piration, 468 
Intermediary  substance  of  nerve,  116 
Internal  car,  771 
secretions,  951 
classification,  952 
of  gastric  mucosa,  967 
of  genital  organs.  981 
of  intestinal  mucosa,  967 
Interoceptors,  general,  730,  752 

special,  730,  743 
Interpolated  systole,  343 
Interrupter,  Xeff's,  64 
Interv^ertebral  ganglion,  619 
Intestinal    bacteria,     reaction     of,     on 
carbohydrates,  997 
on  fats,  997 
on  proteins,  998 
canal,  absorption  from,  1027 
glands,  948 
juice,  938 
function,  997 
secretion  of,  949 
mucosa,  internal  secretion  of,  967 
Intestine,  large,  divisions  of,  1010 
movements  of,  1017 
small,  movements,  1013 
p>endular  motion,  1014 
Intestines,  movements,  1013 

fluoroscopic  examination,  1013 
nervous  control,  1015 
vasomotor  nerves  of,  437 


Intra-abdominal  pressure,   changes  in, 

478 
Intra-auricular  pressure,  297 
filling  of  auricles  in,  299 
Intracardiac  pressure,  change.^  in,  292 
diastolic,  296 
mean,  296 

methods  of  registration,  292 
systolic  pressure,  296 
Intracranial  pressure,  441 
Intramural  circulatory  system,  428 
Intraocular  pressure,  805,  810 
Intrapleural  pressure,  457 
Intrapuhnonic  pressure,  457 

changes  in,  478 
Intrathoracic  pressure,  457 
cause  of  negativity  of,  460 
changes  in,  477 
Intravascular  clotting  of  blood,  217 

lymph,  233 
Intraventricular  pressure,  300 
Intrinsic  muscles  of  inspiration,  466 
Inversion  of  retinal  image,  848 
Invertase.  950 
Invertin,  931 
Inverting  enzymes,  989 
lodothyrin,  952,  960 
Ionization  theory  of  activation  of  oxy- 
gen, 511 
Iris,  811 

function,  812 
innervation  of,  817 
Irritability  of  muscle,  independent,  52 
of  nerve,  124 

conductivitv   and,    differentiation, 
124" 
of  protoplasm,  35 
Ischiocavernosus  muscle,  1127 
Islands  of  Langerhans,  932,  965 
Isometric  myograms,  56 
Isosmotic  solution,  1025 
Isotonic  myograms,  56 
solution,  1025 

Jacksoniax  epilep.sy,  677 

Jacobson's  nerve,  912 

Janeway's  sphj^gmomanometer,  369 

Jaw  jerk,  599 

Jejummi,  1036 

Jenson's  theorv  of  muscle  contraction, 

50 
Johannson    and    Tigerstedt's  cardiom- 

eter,  304 

K.^RYOKINESIf?,    1111 

Kephalin,  222 

of  nerve,  114 
Kephir,  901 
Ketosis,  1043 
Kidnej'  oncometer,  398 

structure,  1064 

vasomotors  of,  435 
IGnase,  170,  990 
Knee-jerk,  599 
Konig's  resonator,  762 


INDEX 


1165 


Koumiss,  901 

Krause's  corpuscle,  735,  736 

Ivries'  apparatus  for  recordiriR  capillary 

prcssuro.  37(5 
Krogh's  niiorotonometer.  401 
Kiihne's    method    of    proving    double 

nerve  conduction,  127 
Kupfer's  stellate  cells,  207,  939 

Labial  sounds,  554 
Labor,  1444 

abdominal  press  in,  1145 

average  duration,  1145 

effect  of,  on  arterial  blood  pressure, 
371 

pains,  1144 

stages,  1145 
Labyrinth,  763 

of  ear,  771 

osseous,  771 
Labyrinthine  reflexes,  789 

tonus,  7<S9 
Lacrimal  glands,  807 
secretion,  807 

lake,  808 
Lactalbumin,  902 
Lactase.  990,  997 

Lactation,  mammary  glands  during,  899 
Lacteals,  235 
Lactic  acid  of  muscle,  87 

formation,  88 
Lactoglobulin,  902 
Lactose,  902 
Ladd-Franklin  theory  of  color  vision, 

887 
Laennec's  stethoscope,  757 
Lake,  lacrimal,  808 
Laked  blood,  181 

Lamella,     anterior     homogeneous,     of 
cornea.  805 

posterior  homogeneous,  of  cornea,  805 
Lamina  basilaris,  775 

dental.  1001 

spiralis,  772 
Langenbeck's  proof  of  accommodation 

of  eye.  824_ 
Langerhans,  islands  of,  932,  965 
Larvngeal  branch  of  vagus,  superior, 
'534 

branches  of  vagus,  inferior,  535 

chamber,  540 
Larynx,  540 

artificial,  551 

cartilages  of,  541 

examination  of,  in  reflected  light,  550 

general  structure,  541 

innervation  of,  535,  547 

ligaments  of,  541 
Laughing.  482 
Law,  Bell-Magendie,  620 

of  degeneration,  Wallerian,  621 

Weber's,  733 
Lecithin,  948 

in  blood,  169 

of  nerve,  114 


Lecithoprotein,  217 

L('u;lanche  cell,  57 

Leech  extract,  effect  of,  on  coagulation 

of  blood,  225 
Lens,  biconcave,  800 
refraction  by,  803 

biconvex.     See  Biconvex  lens. 

crystalline,  820 

changes    in    shape    and    refractive 

power,  827 
wabbling  of,  826 
Lenses,    achromatic,    of    Dollard,    816 

refraction  by,  799 

varieties,  799 
Leukocytes,  200' 

basophilic,  200 

diapedesis,  206 

eosinophilic,  200 

mononuclear,  200 

polymorphonuclear,  200 

polynuclear,  200 

transitional  type,  200 
Leukocytosis,  201 

assimilation,  201 

pathological,  201 
Leukocythemia,  904 
Leukopenia,  201 
Levers,  different  systems,  47,  48 
Levdig,    cells  of,    interstitial,   function, 

984 
Lieberkiihn,  crypts  of,  908,  949 
Life,  general  conditions,  33 
phenomena,  29 

spontaneity  of,  33 

structural  basis  of,  21 
Ligaments  of  larynx,  541 
Light,  cause  of,  794 

corpuscular  theory,  794 

emission  theory,  794 

nature  of,  794 

qualities  of,  879 

reflection  of,  795 

reflex,  648,  812 

sources  of,  794 

stimulation  by,  chemical  and  physical 
changes  in  retina  from,  840 

undulatory  theory,  794 

velocitv  of,  794 

white,  879 
Lindemann's    method    of    determining 

quantity  of  blood,  228 
Linea  diaphragmatica,  464 
Lines,  Zollner's,  878,  879 
Lingual  tonsils,  907 
Linguopalatal  sounds,  554 
Lipase,  513.  935 

of  saliva,  994 
Lipins  of  muscle,  86 
Lipochrome,  171 
Lipoids,  25 

of  nerve,  114 
Lipolvtic    action    of    pancreatic   juice, 
996 

enzymes,  989 
Lippmann's  capillary  electrometer,  101 


1166 


INDEX 


Liquid,  flov/  of,  through  elastic  tubes, 
351 
through  rigid  tubes,  349 
Liquor  amnii,  1140 

folliculi,  1129 

spinalis,  60.5 
Lissauer's  bundle,  616 
Liver,  938,  951,  964 

blood  supply,  938 

disintegration  of  red  corpuscles  by. 
198 

extirpation,  945 

function,  940 

internal  secretory  power,  964 

origin  of  urea  in,  1084 

vasomotor  nerves  of,  438 
Living  substance,  17 

metabolic  function,  20 
reproduction  of,  32 
Lobes  of  glands,  892 
Lobules  of  glands,  892 
Lobuli  complicati  of  cerebellum,  706 
Lobulus    medianus    posterior    of    cere- 
_  bellum,  706 

simplex  of  cerebellum,  706 
Lobus  quadratus  anterior  of  cerebellum, 

706 
Localization,  cerebellar,  713 

cerebral,  671,  681 

tactile.  736 
Locomotion,  action  of  striated  muscle 
in,  46 

lever  movements  in,  47 
Loring's  ophthfilmoscope,  864 
Low  fever,  1106 

Lower  extremity,  motor  points  in,  153 
Ludwig's    filtration   theory  of  urinary 
secretion,  1067 

mechanistic  theory  of  secretion,  892 

stromuhr,  395 

theory   of  formation  of  lymph,   237 
Lumbar  puncture,  720 
Luminiferous  ether,  794 
Luminosity,  880 
Lung,   air-cells  or  alveoli  of,    451 

amphibian,  451 

birds',  451 

capacity,  estimation  of,  481 

changes  in  position,    in   respiration, 
475 

collapse,  457 

complex,  451 

elementary,  447,  448 

structure  and  function,  445 

general  topography,  454 

mammalian,  452 
Lungmotor,  484 
Lutein,  171 

Luxus  consumption,  1057 
Lymph,  158,  233 

as  protective  mechanism,  245 

augmentation  of  flow,  240 

constituents,  235 

factors  controlling  flow,  243 

formation,  233,  237 


Lymph,  intravascular,  233 

properties,  233,  234 

sources,  237 
Lymphagogues,  240 
Lymphatic  secretions,  903 
Lymphatics,  distribution  of,  234 
Lymphocytes,  types,  200 
Lymph-hearts  of  amphibia  and  birds, 

244 

Macrocttes,  175 
Macrophages,  198 
Macrosmatic  animals,  690 
Macula  acustica,  783 

sacculi,  function,  783 

utriculi,  function,  783 
Magnesium  sulphate,  effect  on  speed  of 

nerve  conduction,  133 
Malapterurus,       electrical      organ    of, 

double  nerve  conduction  in,  128 
Male  erectile  tissues,  1126 

reproductive  organs,  1122 
Malleus,  765,  766 
Malpighian  corpuscles,  904 
Maltase,  950,  990,  997 
Mammalian  lung,  452 
Mammals,  alimentary  canal  of,  998 

circulatory  system  in,  258 

spinal  reflexes  in,  595 
Mammary  glands,  897 
during  lactation,  899 
effect  of  pituitrin  on,  979 
histological  character,  898 
in  pregnancy,  898,  1138 
innervation  of,  899 
relation  to  female  sexual  organs, 
899 
Mammillary  reflex,  598 
Man,  normal  diet  of,  1058 
Manometer,  membrane,  296 

mercury,  293, 
Marey's  pneumograph,  473 

sphygmograph,  382 

tambour,  285 
Mast-cells,  200 
Mastication,  998,  1000 

center  for,  641 
Mastoid  antrum,  764 

cells,  764 
Mate,  1063 
Material,  animate,  19 

inanimate,  19 
Matteucci's  current  of  rest,  103 
Mayer  curves,  393 

theorj^  of  muscle  contraction,  49 
Maximal  stimuli,  34 
Maxwell's  color  wheel,  880 
McDougall's  theory  of  muscle  contrac- 
tion, 50 
Meatus,  auditory,  763 

external,  764 
Mechanical  block  theory  of  sleep,  723 

imprint   theory  of  light   stimulation 
of  retina,  840 

stimuli,  33 


INDEX 


11G7 


Mechanical    theory    of  urinary  secr(>- 

tion,  facts  contradict iiifr,  IDdS 
Mechanistic  theory   of  fat  al)sor|jtioii, 
1031 
of  secretions,  892 
Media,  transparent,  795 
Mediastinum,  455 
MeduUa  ohlonsata,  640 

as  automatic  center,  641 
as  reflex  center,  640 
function,  640 
MeduHary  sheath  of  nerve,  111 
substance  of  nerve-fiber,  113 
Mep;akarvocvtes,  210 
Mepilocytes",  175 
Meibomian  glands,  809 
Meigg's  theory  of  muscle  contraction, 

50 
Meissner,  corpuscles  of,  734 
Membraua  granulosa,  1130 

vestibularis,  775 
Membrane,  basal,  775 
basilar,  772 
manometer,  296 
nictitating,  807 
of  Reissner,  775 
tectorial,  777 
tympanic,  765 
Membranous  canal  of  cochlea,  775 
Mendel's  law,  1120 
Mendenhall    and    Cannon's  coagulom- 

eter,  220 
Meniere's  disease,  790 
Menopause,  1132 

Menstrual  blood,  coagulability  of,  226 
Menstruation,  1132 

effect  of,  on  arterial  blood  pressure, 

371 
ovulation  and,  relation,  1133 
symptoms  during,  1132 
theories  of  cause,  1133 
Mercury  manometer,  293 
Mesencephalon,  664 
Mesenteric  artery,  inferior,  433 

superior,  433 
MesoporphyriB,  189 
Metabolic    function   of  living    matter, 
20 
requirements  of  body,  1052 
Metabolism,  29,  30,  985 
effect  of  adrenalin  on,  975 
of  age  and  sex  on,  1054 
of  muscular  exercise  on,  1054 
of  sleep  on,  1054 
of  temperature  on,  1054 
excessive,  1057 
factor  of  growth  in,  1059 
normal,  1055 
of  carbohvdrates,  1038 
of  fats,  1044 
of  proteins,  1048 

end  products  of,  1050 
specific   dynamic  action  of  proteins 
in,  1059 
Metaphase  of  mitosis  of  cell,  1111 


M(>tchnikoff's  phagocytosis,  39 
Metcstrum,  1133 
Meth('mogloi)in,  186 

spectrum  of,  194 
Methyli)rnpyl|)vrrol,  189 
Micro-calorimeitcrof  Hill,  1092 
Microcytes,  175 
Microscope,  examination  of  circulation 

by,  408 
Microsmatic  animals,  690 
Microtonomcter,  Krogh's,  491 
Micturition,  abclominal  press  in,  1077 
mechanism  of,  1077 
reflex  center  for,  596,  1077 
spinal  center  for,  596 
Midbrain,  663,  664 

reflex  inhibition  bj'-,  589 
Middle  ear,  763,  764 
Migration  of  ovum,  1135 

of  spermatozoa,  1136 
Milk,  alcoholic  f(>rmentation,  901 
amount  required  by  infant,  901 

secreted  by  mother,  901 
carbohydrate,  902 
coagulation,  901 
composition,  901 
cow's,  humanized,  903 
human  and  cows'   comparison,   902, 

903 
properties,  900 
protein,  902 
salts  of,  902 

skin  formation  from  boiling,  901  • 
teeth,  1001 
Milk-curdling     action     of     pancreatic 
juice,  996 
of  saliva,  994 
Milk-sugar,  902 
Mind-blindness,  688 
Mind-deafness,  688 
Minimal  air,  481 

stimuli,  34 
Miosis,  817 

Mirror,  plane,  reflection  from,  796 
spherical,   796.     See   also    Spherical 
mirror. 
Mitosis,  1111 
Mitral  valve,  268 
Moderator  bands,  267 
Modiolus,  772 

Molecular  motion,  Brownian,  37 
theory  of  current  of  injury,  104 
Monakow's  bundle,  616 
diaschisis  effect  of,  701 
Mononuclear  leukocytes,  200 
Monosaccharides,  987 
Monticulus  of  cerebellum,  706 
Morgagni,  ventricles  of,  545 
Morse's  key  for  making  and  breaking 

electrical  current,  61 
Morula,  1119 

Moss  fibers  of  cerebellum,  708 
Mosso's  ergograph,  81,  82 

plethysmograph  for  arm,  399 
Motion,   36.     See  also   Movement. 


1168 


INDEX 


Motor  aphasia,  694 
area  a  true  center,  676 
ablation  of,  effects,  679 
of  cerebrum,  671 
location,  673 
Motor  end-organ  or  effector,  location  of, 
415 
neuron,  109 
paralysis  from  hemisection  of  spinal 

cord.  626 
points  in  lower  extremity,  153 
in  upper  extremity,  152 
Motor-plate  of  muscle.  51 
Mountain  sickness.  519 
]Mouth-to-mouth    method    of   artificial 

respiration,  484 
Movement,  36 
ameboid,  38 
by  changes  in  cell  turgor.  37 

in  specific  gravity.  38 
by  growth.  38 
by  secretion,  38 
by  swelling  of  cell-walls.  37 
ciliary.  39 

molecular,  Brownian,  37 
muscular,  42 

period  of  contraction.  43 
of  relaxation,  43 
passive.  36 
sense  of,  785 
types.  36 
Mucin.  907 

action  of,  993 
Mucous  glands,  secretory  product,  907 

secretions,  903 
Mucus.  907 
Miiller's  theorv  of  muscle  contraction. 

50 
Miiller-Lyer  figures.  S7S 
Murmur,  bronchial.  477 

hemic,  780 
Muscse  volitantes,  854 
Muscarin,  effect  on  inhibitor  reaction  of 

heart,  316.  317  j 

Muscle,  abnormal,  reaction  to  constant 
and  interrupted  electrical  currents.   | 
142  ' 

absolute  power  of,  95 
artificial,  of  Engelmann.  49 
as  electrogenic  organ.  98 
as  thermogenic  organ.  97 
bulbocavernosus,  il27 
carbohydrates,  86 
cardiac.  42 
chemistry  of,  85 
ciliary,  innervation  of,  830 
coagulation-rigor,  93 
contracting,  chemical  changes  in,  87 
contraction,  48 
character  of,  70 

factors  varying,  76 
effect  of  drugs  and  chemicals  on, 
79 
of  duration  of  stimulus  on,  77 
of  fatigue  on,  80 


Muscle,*  contraction,  effect  of  load  on> 
77 
of    muscle  substance  on,  77 
of  strength  of  stimulus  on,  76 
of  veratrin  on,  79 

Engelmann's  theory,  49 

fusion,  71 

graphic  registration,  53 

induced,  104 

influence  of  temperature  on,  78 

Jenson's  theory,  50 

McDougalls  theory,  50 

maximal.  77 

Mayer's  theory,  49 

Meigg's  theor}',  50 

minimal.  77 

Midler's  theory,  50 

Ranvier's  theory,  50 

refractory  period.  72 

registration,  muscle-ners'e  prepara- 
tion for,  53 
methods,  54 

Schafer's  theory,  50 

summation,  71 

supramaximal,  77 

tetanic,  72 

thermodvnamic  theorv,  49 

threshold.  76 

Verworn's  theory.  50 

voluntary,  73 

wave.  68 

Weber's  theory,  49 
contracture,  74 

clonic.  75 

tonic.  75 
Crampton's,  822 
cremaster.  1123 
crico-arytenoid.  lateral.  547 

posterior.  547 
different  phases  of  electric  currents 

in,  106 
direct  stimulation,  52 
disappearance  of  glycogen  in,  89 
effect  of  sodium  chlorid  on,  80 
elasticity.  65 
electric  currents  in,  phases,  106 

stimulation.  57 

variations  in.  character,  103 

compensation  method  of  detect- 
ing. 102 
energy,  production  of,  93 
enzymes,  87 
excitation,  51 
extensibility,  65 
extractives,  87 

fatigue,  Treppe  phenomenon,  90 
fiber,  43,  44 

intermediate  discs,  44 

transverse  discs,  44 
fibrillte,  44 

forms  of  energy  liberated  by,  93 
general  composition,  85 
heat  rigor,  79 

thermoelectric  method  of  measur- 
ing. 97 


INDEX 


11G9 


Muscio    human,    dcRonorafod.    law    of 

coiitiat'tioii,  1")") 
indirect  stiiuulatioii,  52 
inorganic  constitiiciits,  SO 
irritaliility  of,  indcpciidcMit.  52 
ischiocavcrnosus,  1 127 
lactic  acid  in,  87 

formation,  88 
lipins,  86 

methods  of  stimulation,  53 
motor  plate,  51 

negative  variation  of  primary  demar- 
cation current  in,  107 
non-striated,  42 

normal   human,   law  of  contraction, 
150 

reaction    to    constant    and    inter- 
rupted electrical  currents,  142 
orbicularis  palpebrarum,  807 
pale,  44 

physiology  of,  17 
pigments,  87 

production  of  carbon  dioxid  by,  88 
proteins,  85 
purins,  87 
red,  44 

retractor  bulbi,  870 
■      lentis,  821 
simple  twitch,  70 

smooth,  character  of  contraction,  83, 
84 

tonicity  of,  83 
sound,  69 

spindles,  function,  784 
stapedius,  765 
stimulation,  unipolar  method,  151 

effects  of,  154 
striated,  42 

action  in  locomotion,  46 
stroma,  85 

proteins  of,  86 
subminimal      stimuli,       summation, 

76 
substance,  effect  of,  on  contraction, 

77 
summation  of  contractions,  340 

of  stimuH,  340 
tensor  tympani,  765 
thyro-arytenoid,  547 
tissue,  cardiac,  46 

effect  of  adrenalin  on,  975 

peculiarities,  65 

smooth,  45 

structure,  43 
tonicity  of,  66 
trophic,  state,  67 
water-rigor,  93 
work  performed  by,  94 
Muscle-curve,  latent  period,  71 
period  of  contraction,  70 

of  relaxation,  70 
Muscle-nerve  preparation  for  register- 
ing muscle  contraction,  53 
Muscle-plasma,  proteins  of,  86 
Muscle-spindle,  51 
74 


Muscles,  of  car,  inherent,  770 
of  inspiration,  466 
accessory,  466 
extrinsic,  466 
intrinsic,  466 
noniuil,  466 
papillary,  267 
Muscular  exercise,  effect  of,  on  arterial 
blood  pressures,  371 
respiratory  quotient  in,  515 
movement,  42 

period  of  contraction,  43 
of  relaxation,  43 
Musculature,  skeletal,  42 

visceral,  42 
Musculi  pectinati,  264 
Musical  sounds,  758 
Mydriasis,  817 
Myelin  sheath  of  nerve,  1 1 1 

function,  116 
Myeloplaxes  of  bone-marrow.  207 
Myocardium,  263 
Myogen,  86 
Myogenfibrin,  86 
Myogenic  theory  of  heart  beat,  334 

of  peristalsis,  1016 
Myograms,  isometric,  56 

isotonic,  56 
Mvographv,  54 
Myoids,  42 
Myopia,  855,  859 
Myosin,  86 
Myosinfibrin,  86 
Myxedema,  957,  958 

Narcosis,  716,  725 

Narcotics,  effect  of,  on  speed  of  nerve 

conduction,  133 
Nasal  sounds,  554 
Nauseating  odors,  747 
Near-point  of  vision,  828 
Near-sightedness,  859 
Neff's  interrupter,  64 
Negative  variation  of  primary  demar- 
cation current  in  muscle,  107 
Neopallium,  665 
Nerve,  abducens,  650 

abnormal,   reaction  to  constant  and 
interrupted  electrical  currents,  142 

accessory,  655 

auditory,  651 

axial  current  in,  136 

axis-cvlinder,  function,  116 

band  fiber,  121 

cells,  fatigue  of,  568 
cause,  570 
inhibition  of,  574 
refractory  period,  571 
summation  of  stimuli  in,  572 

center.  111 

chemistry,  114 

cholesterin,  114 

compression-paralysis,  131 

conduction,  centrifugal,  126 
centripetal,  126 


1170 


INDEX 


Nerve,    conduction,    chemical    theory, 
134 
direction,  125 

double,  in  electrical  organ  of  Ma- 
lap  terurus,  128 
Kiihne's  method  of  proving,  127 
law  of,  126 
electrical  theory  of,  133 
forward,  law  of,  126 
nature  of,  133 
speed,  128 

effect  of  alcohol  on,  133 
of  anesthetics  on,  133 
of  carr)on  dioxid  on,  133 
of  immersion  in  water  on,  132 
of  magnesium  sulphate  on,  133 
of  narcotics  on,  133 
of  temperature  on,  132 
factors  altering,  131 
Helmholtz's    method    of    deter- 
mining, 129 
string    galvanometer   for   meas- 
uring, 130 
wave  of  negativity  in,  134 
theory  of,  133 
conductivity,  124 
current  of  action  in,  137 

of  injury  in,  135 
degeneration,  117 
ascending,  120 
descending,  120 
morphological  changes,  120 
primary,  118 
retrogressive,  119,  122 
secondary,  118,  621 
tertiary,  119 
Wallerian  law  of,  119 
depressor,  325,  329 
dorsalis  penis,  1129 
electrotonic     condition,     method     of 

testing,  146 
energies,  specific,  doctrine  of,  730 
erigens,  1129 
facial,  650 
fatigue,  139,  140 
function,  115 

of  different  parts,  116 
galactosids,  114 
glossopharyngeus,  534,  653 

function,  749 
going  to  sleep,  131 

human,  degenerated  law  of  contrac- 
tion, 155 
hypoglossal,  656 
ileo-inguinalis,  1129 
impulse,  relation  to  wave  of  negativ- 
ity and  action  current,  138 
inorganic  salts  in,  115 
intermediary  substance,  116 
irreciprocal  conduction,  115 
irritability,  124 

conductivity   and,    differentiation, 
124 
kephalin,  114 
lecithin,  114 


Nerve,  liberation  of  energy  bj%  134 
lipoids,  114 
medullary  sheath.  111 
metabolism  during  activity,  138 
methods  of  stimulation,  53 
myelin  sheath.  111 

function,  116 
neurilemma,  function,   117 
normal  human,   law  of  contraction, 
150 

reaction    to    constant    and    inter- 
rupted electrical  currents,  142 
oculomotor,  647 
of  equilibrium,  651 
of  hearing,  651 
of  Jacobson,  912 
olfactory,  644 
optic,  645 

phenomena  of  conduction,   124 
physiology,  17,  108 
plexus,  112 
pneumogastric,  654.     See  also  Vagus 

nerve. 
potassium  in,  115 
primitive  sheath.  111 
proteins,  114 
pudendus,  1129 

reaction    of,    to   ascending    constant 
electric  current,  142 

to  descending  constant  electric  cur- 
rent, 142 

to  polarization  current,  142 
receptor  substance,  116 
refractory  period,  lengthening  of,  141 
regeneration,  122 

embryonic  fibers  in,  123 

morphologic  changes,  122 
stimulation,  unipolar  method,   151 

effects,  154 
structure.  111 
tetanus  of,  secondary,  148 
tissue,  assimilative  changes,  139 

dissimilative  changes,  139 

refractory  period,  139 
trigeminus,  534,  649 
trochlear,  649 

vagus,  654.     See  Vagus  nerve. 
Nerve- fiber,  111 
axis  cylinder,  113 
band,"  121 

degenerating,  histology,  123 
end-organs,  113 
medullary  substance,  113 
neurilemma,  113 
retrogressive  degeneration,  611 
thickness,  112 
Nerve-fibrils,  112 
Nerves,  cranial,  642 

functional  system  of,  642 
glossopharyngeal,  534 
in  lower  extremity,  153 
Nervous    depressants,    effect   on   body 

temperature,  1106 
regulation  of  respiration,  528 
system,  anatomia  division,  557 


INDEX 


1171 


Nervous  system,  autonomic,  627 
actiou  of  I'piuc'pliriu  on,  1)74 
alTcront  conduction  in,  035 
cerelirospinal   system    and,   con- 

noctions  hotwocn,  03 1 
cluiract  oristics,  02'.) 
function,  030 
central,  .'j.'j? 
mass,  ,5.'37 
cerebrospinal,  autonomic  system 
and,  cotmections  between,  631 
cervical  sy  in  pathetics,  031 
chemical  t^rounds,  .557 
cranial,  031 

fibrillar  hypothesis,  565 
functional  arrangement,  565 
Rrounds,  557 
significance,  557 
unit,  574 
histological  grounds,  557 
joining  of  reflex  circuits,  580 
lessening    irritabihty  of,   reflex  in- 
hibition from,  590 
neuron  concept  of,  558 
parasympathetic,  027,  031 
peripheral  complex,  557 
protective  mechanisms,  700,  710 
reflex  circuit,  575 
concept,  574 

evolution  into  reaction  system, 
578 
rudimentiary,  a  reflex  system,  370 
sacral  sympathetic,  031 
structural  arrangement,  557 

unit,  558 
subdivisions,  557 
sympathetic,  027 
thoracic  sympathetic,  631 
visceral,  621 

Waldeyer's  neuron  doctrine  of,  565 
arguments  in  favor,  567 
Nervus  accelerans,  310 

perinei,  1129 
Neurilemma,  111 

of  nerve,  function,  117 
of  nerve-fiber,  113 
Neurit,  108 
Neuroblast,  108,  559 
Neurogenic  theory  of  fever,  1107 
of  heart  beat,  332 
of  peristalsis,  1016 
Neuroglia,  108 
Neurokeratin,  113 
Neuron,  108,  558 
afferent,  109 

concept  of  nervous  system,  558 
conducting  paths,  108 
doctrine    of    nervous    system,    Wal- 
deyer's, 565 
arguments  in  favor,  567 
efferent,  109 

external  characteristics,  558 
form  and  size,  108 
function,  109 
internal  characteristics,  503 


Neuron,  motor,  109 

sensory,   109 

types  of,  500,  501,  502 
Neutral  salts,  elTect  of,  on  coagulation 

of  blood,  223| 
Neutropliilc  graiudes,  200 
Neutrophiles,  199 
New-born  infant,  respiration  in,  400 
Newton's       emission     or     corpuscular 

theory  of  light,  794 
Nicotin,  effect  on  inhibitor  reaction  of 
heart,  310 
on  salivary  secretion,  910 
Nictitating  menibrane,  807 
Nissl's  granul(!s,  108,  503,  504 
Nitric  oxid   hemoglobin,   spectrum   of, 

194 
Nitrogen,  amino-,  1051 

elimination  of,  in  starvation,  1053 

excretion     of,     pn^mortal     rise,     in 
starvation,  1053 

function,  447 

in  blood,  condition  of,  507 

relation    to    sulphur,    in    starvation 
1053 
Nitrogen-equilibrium,  1049 
Nobili's  galvanometer,  99 
Node,  sino-auricular,  277 
Nodes  of  Ranvier,  113 
Noises,  757 

perception  of,  780 
Non-polarizable  electrodes,  59 
Non-striated  muscle,  42 
Non-threshold  substances,  1073 
Normoblasts,  197 
Novain,  87 
Nuclein,  20,  29 
Nucleoproteids,  20 

tissue,  222 
Nucleoprotein,  171 
Nucleus  in  central  nervous  system,  111 

of  cell,  24 

cytoplasm  and  functional  relation, 
27 

cleavage,  1119 

segmentation,  1119 

Obesity,  1047 

Banting's  cure,  1050 
Occipitofrontal  fasciculus,  061 
Oculomotor  nerve,  047 
Odors,  classification,  747 
Odores  factores,  747 

intermediae,  747 

suaveolentes,  747 
Ohm,  58 

Old-sightedness,  830 
Olein  of  milk,  902 
Olfactometer  of  Zwaardemaker,  746 
Olfactometry,  745 
Olfactory  bulb,  044 

cells,  power  of  reaction,  745 
specific  action,  744 

center,  044,  690 

nerve,  644 


1172 


INDEX 


Olfactory  nucleus,  secondarj-,  644 
organ,  structure,  743 
sensations,  qualitative  differences  in, 

747 
tract.  644 
Oligocythemia,  180 
Olivospinal  tract,  616 
Oncometer,  kidney.  398 

splenic.  398 
Oocyte.  1129 
Opaque  bodies,  795 
Ophthalmodiaphanoscopy,  864 
Ophthalmometer,  Helmholtz's.  858 
Ophthalmoscope  for  testing  refractive 
power  of  eve.  863 
Helmholtz's,"863 
Loring's.  864 
Ophthalmoscopy,  direct,  864 

indirect.  867 
Opsonic  index.  206 
Opsonins,  205 

Optic  defects  of  eye,  acquired,  855 
inconstant,  855 
disc,  834 
illusions,  876 
nerve,  645 
thalamus,  703 
Optics,  794 

physiological,  794 
Optimum  stimuli,  34 
Optogram,  842 
Ora  serrata,  806.  831 
Orbicularis    palpebrarum   muscle.    807 
Organ  of  Corti,  activation,  777 
function,  777 
structure.  775 
Orgasm.  1136 
Ornithin,  1084 
Osmatic  animals,  690 
Osmometer,  1023 
Osmosis,  1023 
Osmotic  pressure,  1024 

stimuli,  33 
Osseous  canal  of  cochlea,  772 

labyrinth  of  ear,  771 
Ossicles,  764,  766 

movements,  767 
Otocyst,  781 
Otolithic  ca\atv,  781 
Otoliths,  781 
Ovaries.  1129 

function,  981 
Overtones,  fundamental,  759 
Ovists.  1117 
0\'ulation,  menstruation  and,  relation, 

1133 
0^'um.  1117 

fertilization  of,  1118 
implantation  of,  1137 
migration  of,  1135 
polar  bodies  of,  1118 
spermatozoa  and,  place  of  meeting, 
1137 
Oxidase,  513 
Oxidations,  hydrohiiic,  511 


Oxidations  of  ferments,  991 

seat  and  nature,  508 
Oxidative  glycosuria,  966 

power  of  tissues,  508 
Oxidizing  enzymes,  989 
Oxygen,  activation  of,  theories,  511 

and  hemoglobin,  compounds  of,  prop- 
erties, 185 

deficiency,  effects  of,  519 

diminution  in  partial  pressure,  effect 
on  respiratory  quotient,  517 

electronegative,  510 

in  blood,  condition  of,  502 

increase    in    partial    pressure,    effect 
on  respiratory  quotient,  517 

ingo  in  starvation,  1053 

requirement  of  fetus,  1142 

respiratory,  445 
Oxyhemoglobin.  183 

preparation  and  quantity,  184 

spectrum  of.  193 
Oxyntic  cells  of  gastric  glands.  920 
Ozone-autozone  theory  of  activation  of 

ox3'gen,  511 

Pacinian  corpuscles,  734 
Pace-maker.  315 

of  peristalsis.  1015 
Pain,  sense,  734,  740 
Pains,  labor,  1144 
Pale  muscle,  44 
Pallium,  665 
Palmitin  of  milk,  902 
Palpation  method  of  recording  arterial 

blood  pressure,  366 
Palsv,  diver's,  522 
Pancreas,  932,  951,  965 

histological  changes  in  cells  of,  during 

secretion,  933 
internal  secretion  of,  function,  966 
removal  of,  965 
vasomotor  nerves  of.  438 
Pancreatic  duct.  932 
glycosuria.  966,  1043 
juice,  amylolytic  action,  996 
character  of,  935 
enzymes  of,  935 
function,  995 
lipolytic  action,  996 
methods  of  procuring,  933 
milk-curdling  power,  996 
proteolytic  power,  995 
secretion,  regulation  of,  935 
secretions,  918 
Papillary  muscles,  267 
Parabiosis,  1116 
Paraglobulin,  170.  171 
Paragraphia,  698 
Paralytic  secretion  of  saliva,  911 
Paraphasia,  694 
Parasympathetic  system,  631 
Parathyroid  glands,  951,  954 
extirpation,  955 

symptoms  from.  956 
function,  961 


INDEX 


1173 


Parathyroid  filands,  position,  955 

structure,  «»55 
Parhormoiu's,  \i5'd 
PiirieUil  cflls  of  gastric  glands,  920 

pleuni,  4.')5 
Parotiil  salivary  glands,  UOS 
Pars  intt'riiu'tliu,  977 
Partlienogcncsis,  1117,  1119 

artilicial.  1119 
Parturition,  1144 
Passive  ininuinity,  24G 

motion,  36 
Patellar  reflex,  599 

nature,  599 
Peduncle,  inferior,  of  cerebellum,  710 
middle,  of  cerehellum,  709 
superior,  of  cerebellum,  709 
Pendular  motion  of  small  intestine,  1014 
Penis,  1127 

erection  of,  1127 
Pepsin.  924 
Peptonization,  effect  of,  on  coagulation 

of  blood,  224 
Perception  reflexes,  592 
Percussion,  476 
Perhydridase,  513 
Pericardial  fluid,  237,  263 

sac,  255 
Pericardium,  function,  264 
Perilymph,  771 
Perimeter.  851 
Perimetry,  851 
Perimysium,  43 
Perineurium,  111 
Periodic  reflexes,  592 
Periosteal  reflexes,  599 
Peristalsis,  myogenic  theory,  1016 
neurogenic  theory,  1016 
pacemaker  of,  1015 
Peristaltic  wave,  1014 

regular,  1014 
Peritoneal    cavity,     absorption    from, 

1033 
Pernicious  anemia,  905 
Peroxidase,  513 
Pfeffer's   experiment    in    phagocytosis, 

204 
Pfliiger's  aerotonometer,  490,  491 
law  of  contraction,  146,  148,  149 
theorv  of  sleep,  724 
Phagocytes,  204 
Phagocytosis,  203 

Pfeffer's  experiment,  204 
in  immunity,  247 
Pharyngeal  reflex,  598 
thirst,  755 
tonsils,  907 
Phenomenon  of  Purkinje,  880 
Phlebogram,  388 
Phloridzin  glycosuria,  1043 
Phonating  organs,  general  arrangement, 

540 
Phonation,  549 
Phosphates  in  urine,   1082 
Phosphatides,  25 


Phosphcnos,  844 
Phospholipin,  217 
PhospholipiiLs  of  bile,  948 
Photic  stimuli,  33 

Photo-liciiHjtachometcr,  Cybulski's,  405 
PhyllopDrphyrin,  189 
Physiology,  definition,  17 
history  of  science,  18 
scope,  17 
Pia  mater,  716 
Pioron's  theory  of  sleep,  724 
Pigments,  muscle,  87 
Pilocarpin,  effect  of,  on  salivary  secre- 
tion, 916 
Pineal  gland,  980 

position  and  function,  980 
Pinna,  763 
Pitch  of  sounds,  758 
Pithing,  530 
Pitot's  tubes,  405 
Pituitary  gland,  977 

anterior  lobe,  function  of,  979 
position,  977 

posterior  lobe,  function  of,  978 
removal  of,  effects,  977 
structure,  977 
Pituitrin,  978 

effect  on  mammary  gland,  979 
on  uterus,  978 
Placenta,  1140 

development,  1140 
function,  1141 
interchange  of  gases  in,  451 
Plane  mirror,  reflection  from,  796 
Plano-concave  lens,  800 
Plano-convex  lens,  800 
Plantar  reflex,  599 
Plasma  of  blood,  159 

corpuscles  and,  relative  amount,  159 
salted,  223 
Plasmozym,  215 
Plate,  refraction  by,  799 
Platelets,    blood,    159,   207,   208,    214. 

See  also  Blood  platelets. 
Plethora,  hydremic,  1074 
Plethj-smograph,  air,  Schafer's,  398 
detection  of  vasomotor  action  by,  420 
glass,  400 

Mosso's,  for  arm,  399 
Plethysmographic  method  of  estimating 

blood  suppl}',  398 
Pleura,  455 
parietal,  455 
visceral,  455 
Pleural  cavity,  complementary,  462 
Pleurisy,  457 
Plexus  cardiacus,  310 
gastricus  anterior,  434 
posterior,  434 
ventralis,  434 
hepatic,  939 
nerve,  112 
renalis,  435 
Solaris,  434 
suprarenalis,  434,  968 


1174 


INDEX 


Plica  semilunaris,  808 
Pneuniatogram,  473 
Pneuniatof^raph,  Gad's,  480 
Pneumogastric    nerve,    654.     See    also 

Vagus  nerve. 
Pneumograph,  Marey's,  473 
Pneumonia,  477 
Pneumothorax,  457 
Pohl's  commutator,  61 

pole  changer,  61 
PoikUocytes,  175,  176 
Poikilothermal  animals,  1093 
Poiseuille's  manometer,  293 
Poisons,  snake,  effect  of,  on  coagulation 

of  blood,  225 
Polar  bodies  of  ovum,  1118 
Polarization  current,  reaction  of  nerve 
to,  142 

external,  143 

in  voltaic  cell,  58 

internal,  143 
Polarizing  current,  144 
Pole-changer,  Pohl's,  61 
Policemen  of  blood,  204 
Pollutions,  seminal,  1129 
Polycythemia,  163,  180 
Polymorphonuclear   leukocytes,    200 
Polynuclear  leukocytes,  200 
Polypnea,  525 

heat,  1095 
Pomum  Adami,  542 
Portal  circuit  of  circulatory  system,  259 

circulation,  433 

vein,  259 
Porus  opticus,  834 

Position,    change  of,  effect  on    arterial 
blood  pressure,  372 

sense  of,  781 
Post-anelectrotonus,  144 
Post-catelectrotonus,  144 
Posterolateral  tract,  613  i 
Posteromedian  tract,  613 
Potassium  in  nerve,  115 

theory  of  cardiac  inhibition,  320 
Precipitins,  248 
Preformation   theory  of   reproduction, 

1117 
Pregnancy,  1138 

effect  of,  on  arterial  blood   pressure, 
371 
on  general  health,  1139 

mammarv  glands  in,  898,  1138 

signs  of,  1138 

uterus  at  end  of,  1138 

uterus  during,  1138,  1139 

vomiting  of,  1139 
Premenstruation,  1133 
Prepuce,  1127 
Prepvramidal  tract,  616 
Presbyopia,  830,  855 
Press,  abdominal,  479,  531,  1011 
in  labor,  1145 
in  micturition,  1077 
Pressure,  diffusion,  446 

head-,  350 


Pressure,  intra-abdominal,  changes  in, 
478 

intracranial,  441 

intra-ocular,  805,  810 

intrapleural,  457 

intrapulmonic,  457 
changes  in,  478 

intrathoracic,  457 

cause  of  negativity,  460 
changes  in,  477 

lateral  or  side,  349 

osmotic,  1024 

resistance-,  350 

sense,  734 

sources,  347 

velocity-,  350 
Preyer's  chemical  theory  of  sleep,  724 
Priapismus,  1128 
Primitive  sheath  of  nerve,  111 
Primordial  follicles,  1129 
Prism,  refraction  by,  799 
Prismatic  spectrum,  879 
Prochymosin,  925 
Pro-estrum,  1133 
Proferment,  215,  990 
Projection  system  of  cerebrum,  660 
Prophase  of  mitosis  of  cell,  1111 
Proprioceptors,  730 
Prorennin,  925 
Prosecretin,  936 
Prosencephalon,  664 
Prostate  gland,  1126 
Protease,  513 
Proteins,  26 

absorption  of,  1031 

circulating,  1048 

diffusion  of,  1026 

endogenous,  1049 

exogenous,  1049 

metabolism  of,  1048 
end-products  of,  1050 

of  body,  source,  1048 

of  milk,  903 

of  muscle,  85 

of  muscle-plasma,  86 

of  muscle-stroma,  86 

of  nerve,  114 

reaction  of  intestinal  bacteria  on,  998 

specific  dynamic  action,  1059 
in  metabolism,  1059 

tissue-,  1048 

utihzation,  1049 
Proteolytic-enzyme  of  saliva,  994 

enzymes,  989 

propertv  of  pancreatic  juice,  995 
Prothrombin,  213,  215 
Protocerebron  of  crayfish,  580 
Protoplasm,  22 

alternate  contraction  and  expansion, 
38 

conductivity,  35 

contractility,  35 

irritability  of,  35 

of  cell.  21 

theories  of  structure,  24 


INDEX 


1175 


Pseudoglobulin,  172 
Pseudouucleoli  of  cell,  25 
Pseutlupoiliii,  203 
Pscudo- reflexes,  637 
Psychie  l)liiuhie.ss,  688 
feeding    for  studv   of  gastric  juice, 
930 
Psycho-auditory  region,  680 
Psychojjhysical  law  of  Pechncr,  733 
Psvchovisual  region,  684 
Ptvalin,  909,988 
action  of,  993 
Ptyalinogen,  909 
Puberty,  1125 

Pulmonary  circuit  of  circulatory  sys- 
tem, 260 
circulation,  430 
Pulmotor,  484 

Pulse,  arterial,  377.     See  also  Arterial 
pulse. 
pressure,  386 

venous,  388.     See  also  Venous  pulse. 
Pulsus  alternans,  388 
bigeminus,  388 
celer,  387 
deficiens,  387 
durus,  387 
frequens,  387 
iaequalis,  387 
intercurrens,  388 
intermittens,  387 
magnus,  387 
mollis,  387 
parvus,  387 
rarus,  387 
tardus,  387 
Punctum  proximum  of  vision,  828 

remotum  of  vision,  828 
Puncture,  lumbar,  720 
Pupil,    constriction    of.    in  anesthesia, 
814 
dilation  of,  spinal  center  for,  596 
drugs  constricting,  814 
dilating,  814 
Purin  bodies,  1051 
bases  in  urine,  1087 
excretion  in  starvation,  1053 
of  muscle,  87 
Purkinje,  cells  of,  560,  708 
figures  or  images,  839 
phenomenon,  880 
Purple,   visual,    840.     See  also    Visual 

purple. 
Pus-corpuscles,  201 
Pycnometer,  162 
Pylorus,  movements  of,  1005 
P\Tamidal  cells,  560 
spinal  tracts,  615 
tract,  661 
Pyrexia,  1106 

Quixcke's     method     of     determining 

quantity  of  blood,  228  j 
Quinquaud  and   Grehant's  method  of 

determining  quantity  of  blood,  227 


Race.mose  glands,  892 
Iladiating  stimuli,  33 
Iladiation,  auditory,  661 
Radiohiria,  20 

Radionxeter,  resistance,  1099 
Rami  vise e rales,  gray,  414 

white,  414 
Ramus  albus  communicans,  633 

griseus  communicans,  633 

sacculo-aiupullaris,  787 

utriculo-ampullaris,  787 
Ranvier's  nodes,  113 

theory  of  muscular  contraction,  50 
Rays,  chemical,  880 

heat,  880 
Reaction,  575 

bimolecular,  992 

Erb's,  156 

galvanotropic,  789 

of  blood,  164 

unimolecular,  992 
Reactions,     paradoxical     temperature, 
743 

voluntary,  110 
Receptor  substance  of  ner\'e,  116 
Receptors,  249 

cutaneous,  structure,  734 

different  types,  583 

somatic,  730 

\'isceral,  730 
Recessus  utricuU,  483,  783 
Recording  stromuhr,  396 
Red  blood   corpuscles,    172.     See   also 
Blood  corpuscles,  red. 

muscle,  44 
Red-blindness,  888 

Reflection  from  convex  spherical  mirror, 
797 

from  plane  mirror,  796 

of  light,  795 
Reflex  action,  109,  583 

animal,  584 

cardiac  death,  326 

center  for  defecation,  1019 
for  micturition,  1077 
spinal  cord  as,  594 

circuits,  110 
joining  of,  580 
of  nervous  system,  575 

concept  of  nervous  system,  574 

croaking  of  frog,  588 

fatigue,  585 

regulation  of  respiration,  533 

scratching,  592 

spinal.     See  Spinal  reflex. 

stimulus,  subminimal,  585 

time,  585 
Reflexes,  110,  575 

accelerating  and  conditioning  of,  591 

accommodation,  648,  812,  814 

alternating,  592 

antagonistic,  592 

association,  582,  592 

axon-,  637 

classification,  591 


1176 


INDEX 


Reflexes,  clonic,  592 
complex,  592 
cremasteric,  592 
crossing,  586 
inhibition  of,  588 

by  afferent  impulses,  589 
by  midbrain,  589 
cerebral,  588 

from  lessening  irritability  of  nerv 
ous  system,  590 
labyrinthine,  789 
light,  648,  812 
perception,  592 
periodic,  592 
pseudo-,  637 
simple,  591 
spastic,  592 
spreading,  586,  592 
threshold,  585 
tonic,  592 

trigeminus  cardiac,  327 
yawning,  593 
Refraction,  798 

by  biconcave  lens,  803 
by  biconvex  lens,  800 
by  plate,  799 
by  prism,  799 
index  of,  798 

of  eye,  abnormalities  in,  853 
Refractive  media,  799 
power  of  cornea,  809 

of  crystalline  lens,  changes  in,  827 
of  eye,  shadow  test,  867 
tests  for,  861 
Refractory  period  of  heart  beat,  341 
Regeneration,  1109,  1113 

of  nerve,  122.     See  also  Nerve  regen- 
eration. 
Regio  olf  actoria,  744 

respiratoria,  744 
Registers,  vocal,  553 
Reissner's  membrane,  775 
Relaxation  period  of  muscular   move- 
ment, 43 
Remak's  ganglion,  318,  332 
Renal  circulation,  433 

glycosuria,  966,  1043 
Rennet,  925 
Rennin,  901,  924 
Reproduction,  1109,  1116 
dynamic  theories  of,  1117 
of  living  substance,  32 
preformation  theory,  1117 
sexual,  1117 
Reproductive  organs,  1109,  1117 
female,  1122 
male,  1122 
Reptile  heart,  257 
Repulsive  odors,  747 
Residual  air,  480 

blood,  229 
Resistance,  245 
Resonance     of     sounds,     sympathetic, 

761 
Resonant  sounds,  554 


Resonator,  Helmholtz's,  762 

Konig's,  762 
Respiration,  445 

abdominal  type,  466 

accessory  movements,  471 

action  of  intercostal  muscles  in,  468 

artificial,  482 

Galliano's  method,  483 
for  animals,  484 
mouth-to-mouth  method,  484 
Sylvester's  method,  483 
Biot,  524 
calorimeter,  1091 

changes  in  position  of  lungs  in,  475 
chemical  regulation  of,  532 
chemistry  of,  486 
Cheyne-Stokes,  523 
costal  type,  466 
diaphragmatic,  type,  466 
external,  447,  487 
in  insects,  448 
in  new-born  infant,  460 
internal,  447,  487,  507 
nervous  regulation  of,  528 
number,  474 
*    of  swallowing,  1002 
reflex  regulation,  533 
self-regulation  of,  538 
tissue,  507 
Respiratory  capacity,  481 
center,  cause  of  activity,  530 
location,  528 
nervous  connections,  528 
regulation  of  activity,  531 
cycle,  455 

dynamic  phase,  461 
function  of  diaphragm  in,  462 

of  ribs  in,  465 
static  phase,  456 
ferments,  513 
interchange,  514 

through  skin,  450 
movements,  461 
character,  472 
frequency,  472 
mechanics  of,  454 
methods  of  recording,  472 
modified,  481 
muscles,  classification  of,  471 
organs,  special,  448 
oxygen,  445 

passage,  upper,  innervation  of,  534 
pause,  456 
quotient,  514 

effect  of  composition  of  air  on,  516 
of  diminution  in  partial  pressure 

of  oxygen  on,  517 
of  external  temperature  on,  516 
of  increase  in  partial  pressure  of 

oxgyen  on,  517 
of  rate  and  depth  of  respiratory 

movements  on,  516 
slight  increase  in  partial  pressure 
of  carbon  dioxid  on,  518 
in  hibernating  animals,  515 


INDEX 


1177 


Respiratory  quotient  in  sleep,  ."jir) 
iiiducnce  of  sex  on,  5 Hi 
vuri.'Uioiis    in,    from    clumietcr    of 
fooil,  ,515 

sounds,  470 

variations  in  blood  pressure,  480 
Resistance-pressure,  3.50 
Respired   air,   quantitative  determina- 
tion, 479 
Resurrection  plant,  37 
Rete  Malpighii,  893 

testis,  1123 
Retina,  800,  831 

blind  spot,  834 

demonstration,  835 
form  of,  830 

chemical  and  physical  changes  in,  on 
stimulation  by  li{i;ht,  840 

corresponding  points  on,  873 

general  structure,  831 

layers  of,  831 

rods  and  cones,  833 

sensibility  of,  to  colors,  884 

yellow  spot,  830 
Retinal  image,  formation,  846,  848 
inversion,  848 
size,  850 
Retinoscopy,  867 

point  of  reversal  in,  868 
Retractor  bulbi  muscle,  870 

lentis  muscle,  821 
Retzius,  fiber  cells  of,  786 
Reversibility  of  ferments,  991 
Revolutio  cordis,  272 
Rheocord,  102 
Rheoscopic      frog     preparation,      104, 

105 
Rhodopsin,  840,     See  also  Visual  pur- 
ple. 
Rhombencephalon,  664 
Ribs,  function  of,  in  respiratory  cycle, 

465 
Rigor,  calcium,  337 

caloris,  79 

chemistry  of,  93 

mortis,  chemistry  of,  91 
Rima  glottidis,  543 

palpebraris,  807 

vocalis,  552 
Ringer's  solution,  182 

effect  on  heart  beat,  336 
Ritter's  tetanus,  146 
Riva-Rocci's  sphygmomanometer,   367 
Rod-granules  of  retina,  832 
Rods  and  cones  of  retina,  833 

of  Corti,  776 
Rolando's  substantia  gelatinosa,  606 
Roof  ganglia  of  cerebellum,  708 
Roots,  hair-,  893 
Rothe's    rotatory    apparatus    for  color 

discs,  881 
Rubrospinal  tract,  616 
Russell  and   Brodie's  method  of    esti- 
mating  coagulation   time   of    blood, 

219 


Sac,  conjunctival,  807 

dental,  1001 
Saccule  of  ear,  771,  782 
Sacral  sympathetic  system,  631 
Saliva,  908 

derivation  of,  909 
fat-splitting  enzyme  of,  994 
function,  993 
general  character,  918 
milk-curdling  power  of,  994 
paralytic  secretion,  911 
proteolytic  enzyme  of,  994 
Salivarv  corpuscles,  918 
glands,  908 

histological  changes  during  activity, 
910 
character,  909 
innervation  of,  911 
parotid,  908 
subungual,  908 
submaxillary,  908 
secretion,  center  for,  641 
of  adrenalin  on,  916 
of  atropin  on,  916 
of  ergotoxin  on,  916 
of  nicotin  on,  916 
of  pilocarpin  on,  916 
filtration     theory     of,     facts     dis- 
proving, 917 
mechanism,  913 
Salivation,  911 
Salted  blood  plasma,  223 
Salts  of  milk,  902 
Sand,  brain-,  981 
Santorini,  duct  of,  932 
Sarcolactic  acid,  1041 
Sarcolemma,  44 
Sarcoplasm,  44 
Sarcostyles,  44 
Scala  tympani,  772 

vestibuli,  772 
Scapular  reflex,  598 
Schafer's  air  plethysmograph,  398 
theory  of  muscle  contraction,  50 
of  structure  of  protoplasm,  24 
Scheiner's  accommodation  experiment, 

827 
Schlemm,  canal  of,  805 
Schonbein  and  Clausius'  ozone-autozone 

theory  of  activation  of  oxygen,  511 
Schultze,  comma  tract  of,  616 
Sciatic  center,  595 

nerve,  vasomotor  reaction,  421 
Sclera,  805 
Scrotal  reflex,  598 
Scrotum,  1122 
Scurvy,  cause,  927 
Sea-sickness,  790 
Sebaceous  glands,  894 
Sebum,  895 
Second  sight,  861 
Secretion,  936 
gastric,  927 
Secretion  externe,  951 
interne,  951 


1178 


INDEX 


Secretion,  histological  changes  in  cells  of 
pancreas  during,  933 

movement  by,  38 

of  urine,  1064.     See  Urine  secretion. 

skin  as  organ  of,  894 
Secretions,  891 

chemical  theory,  892 

classification,  889 

cutaneous,  889 

digestive,  908,  918,  938 

external,  889 

factors  in  formation  of,  892 

filtration  theory  of,  892 

gastric,  918 

internal,     951.     See     also     Internal 
secretions. 

lymphatic,  903 

mechanistic  theory,  892 

mucous,  903 

pancreatic,  918 

vitalistic  theory,  892 
Segmentation  nucleus,  1119 
Semen,  1126 

ejaculation  of,  1127 

pollutions,  1129_ 

spontaneous  emissions,  1128 
Semicircular  canals,  771,  785 
anterior  or  superior,  786 
effects  of  lesions  of,  787 
of  stimulation  of.  788 
external  or  horizontal.  786 
posterior  or  inferior,  787 
relative  position,  786 
Semilunar  valves,  271 
Seminal  vesicles,  1126 
Seminiferous  tubules,  1123 
Semivowels,   sound  production  of,   554 
Sensations,    olfactory,    qualitative   dif- 
ferences in,  747 

tactile,  methods  of  evoking,  735 
Sense,  dynamic,  730,  785 

of  equilibrium,  781 

of  hearing,  756 

of  hunger,  743 

of  movement,  785 

of  pain,  734,  740 

of  position,  781 

of  pressure,  734 

of  sight,  794 

of  smell,  743 

of  taste.  743 

topography  of,  751 

of  temperature,  734,  741 

of  thirst.  743 

of  touch  .734 

static,  578,  730,  781 
Sense-organs,  727 

adaptation  of,  732 

classification,  727,  729 

fatigue  of.  732 
Sensibilin,  252 
Sensitive  plant,  37 
Sensitizing  substance,  250 
Sensory  aphasia,  696 

neuron,  109 


Sensory  paralysis  from  hemisection  of 

spinal  cord,  626 
Septomarginal  bundle,  016 
Sera,  antitoxic,  246 
Serum,  blood,  171,  212 

sickness,  251 
Serum-albumin,  170,  171,  172 
Serum-casein,  171 
Serum-globulin,  170,  171 
Sex,  determination  of,  1143 

effect  of,  on  metabolism,  1054 

influence  of,  on  respiratory  quotient, 
516 
Sexual  glands,  982 

maturity,  1125 

organs,  female,  relation  to  mammarv 
glands,  899 

reproduction,  1117 
Shadow  test  of  refractive  power  of  eye, 

867 
Sham  feeding  for  study  of  gastric  juice, 

930 
Shingles,  622 
Shivering,  1098 
Shock,  589 

theories  of,  590 
Sickness,  mountain,  519 

serum,  251 
Side-chain  theorv  of  immunity,  249 
Sighing,  482 
Sight  center,  684 

nerve  of,  645 

second,  861 

sense  of,  794 
Sigismund's    theorv    of    menstruation, 

1134 
Sign.  Argyll-Robertson,  813 
Singing,  553 

voice,  range,  553 
Sino-auricular  node,  277 
Sinospiral  fibers  of  ventricles,  266 
Sinus  of  Valsalva,  272 

venosus,  255 
Skeletal   muscle  tissue,  vasomotors  of, 
421 

musculature,  42 
Skiascopy,  867 
Skin,  absorption  through,  1034 

as  organ  of  protection,  893 
of  secretion,  894 

cold  spots,  742 

respiratory  interchange  through.  450 

varnishing,  effect  on  body  tempera- 
ture, 1105 

warm  spots,  742 
Sleep,  716,  721 

adult  requirement,  721 

anemia  theory,  723 

changes  in  depth,  722 

chemical  theories.  723 

effect  of,  on  arterial  blood  pressure, 
370 
on  metabolism,  1054 

hypnotic,  724 

inhibition  theory,  723 


INDEX 


1179 


Sleep,  mechanical  block  theory,  723 

phenoiueiia  of,  722 

respiratory  quotient  in,  515 

theories  of,  723 
SmcRnia  preputii,  895 
Smell,  center  for,  690 

nerve  of,  044 

sense  of,  743 
Smith  and  Haldane's  method  of  deter- 
mining quantity  of  blood,  227 
Snake  poisons,  effect  of,  on  coagulation 

of  blood,  225 
Sneezinp;,  482 

center  for,  641 
Snellen's  test  types,  861 
Sniffing,  482 
Snoring,  482 
Sobbing,  482 

Sodiuni  chlorid,  effect  of,  on  muscle,  80 
in  blood,  169 

citrate  method  of  blood  transfusion, 
231 
Solar  spectrum,  879 
Solution,  hyperosmotic,  1025 

hypertonic,  1025 

hyposmotic,  1025 

hypotonic,  1025 

isosmotic,  1025 

isotonic,  1025 

Ringer's,  182 

Stokes's,  186 
Somachrome  cells,  564 
Somatic  cells,  1114 

hunger,  754 

receptors,  727,  730 
Sound,  muscle,  69 

waves,  cause,  756 
character,  756 

conduction  by  cranial  bones,  779 
rate  of  speed,  757 
reinforcement     and     interference, 
760 
Sounds,  757 

color,  759 

intensity,  758 

loudness,  758 

musical,  758 

pitch,  758 

quality,  759 

stamp,  759 

svm pathetic  vibration  or  resonance, 
"  761 

timbre,  759 
.      tone,  758 

vocal.     See  Vocal  sounds. 
Spaces  of  Fontana,  805 
Spastic  reflexes,  592 
Spaying,  effects  of,  982 
Specific  gravity,  movement  by  changes 

in,  38 
Spectrophotometric   method   of    deter- 
mining hemoglobin,  190 
Spectroscope,  192,  193 
Spectroscopic    analysis    of   hemoglobin 

and  derivative  compounds,  192 


Spectrum,  absorption  bands,  192 
Fraunhofer  lines,  1<)3 
of  acid  hcniatin,  195 
of  carl)()n  iiiouoxid  hemoglobin,   194 
of  heiuatopori)hyrin,  195 
of  hemochromogen,  195 
of  luethemoglobin,  194 
of  nitric  oxid  hemoglobin,  194 
of  oxyhemoglobin,  193 
of  reduced  hemoglobin,  193 
solar,  879 
Speech,  540,  553 
center,  691 

location,  693 
circuit,  691 
Spermatids,  1124 
Spermatocytes,  1124 
Spermatogonia,  1124 
Spermatozoa,  1124,  1125 

development  and  character,  1124 
migration  of,  1136 
ovum  and,  place  of  meeting,  1137 
rheotactic  quality,  1136 
thigmotactie  quality,  1136 
Spermatozoon,  1117 
Sperm-cell,  1117 
Spermin,  1126 

action  of,  982 
Spherical  aberration,  815 
mirror,  796 

center  of  curvature,  796 
concave,  796 
convex,  796 

reflection  from,  797  ^ 
geometrical  center,  796 
principal  axis,  797 

focus,  797  _ 
secondary  axis,  797 
Sphincter  antri  pylori,  1005 
of  Henle,  1128 
urethrse  membranaceae,  1128 
Sphygmogram,  383 

clinical  significance,  387 
Sphvgmograph,  Dudgeon's,  382 

Marey's,  382 
Sphygmography,  381 
Sphygmomanometer,  Janeway's,  369 
Riva-Rocci's,  367 
von  Basch,  366 
Spinal      conduction,     localization     of, 

methods  used  for,  609 
Spinal  cord  as  conducting  path,  603 
as  reflex  center,  594 
automatic  activity,  597 
centers,  596 

fasciculi,  classification,  612 
function,  594,  622 
general  structure,  603 
gray  matter,  functional  basis,  606 
hemisection,  effects  of,  626 
posterior  roots,  distribution  of  im- 
pulses from,  623 
roots,  function  of,  519 
tracts,  610 
ascending,  616 


1180 


INDEX 


Spinal  cord  tracts,  classification,  614 
descending,  615 
posterior,  616 
pyramidal,  615 
trophic  function,  603,  621 
vasomotor  reaction  of,  421 
white  matter,  functional  basis,  608 
reflex,  a})dominal,  598 
achillis  jerk,  599 
bulbocavernosus,  599 
centers,  localization,  594 
cremasteric,  598 
gluteal,  598 
jaw  jerk,  599 
mammillary,  598 
patellar,  599 
plantar,  599 
pharyngeal,  598 
scapular,  598 
scrotal,  598 
sternal,  598 
tensor  tj'mpani,  599 
winking,  599 
wrist  jerk,  599 
reflexes,  abolition,  601 
deep,  598 
exaggeration,  601 
from  facial  muscles,  599 
in  mammals,  595 
organic,  598 
periosteal,  599 
reinforcement,  600 
superficial,  598 
Spinocerebellar  tract,  617 
Spinetectal  tract,  681 
Spinothalamic  tract,  618 
Spindles,  muscle,  function,  784 
Spiral  ganglion,  777 
Spirometer,  Hutchinson's,  479 
Wintrich's  modification,  479 
Splanchnic   nerve,    greater,   vasomotor 
reaction  of,  425 
nerves,  function,  434 
system,  435 
Splanchnic!  minores,  435 
Spleen,  903 

disintegration  of  red  corpuscles  bv, 

198 
formation  of  white  blood  corpuscles 

by,  904 
function,  904 

hematopoietic  function,  905 
pulp  of,  905 
removal  of,  effects,  904 
transplantation,  904 
vasomotor  nerves  of,  438 
Splenic  artery,  433 

oncometer,  398 
Sponges,  circulatory  system  in,  254 
Spongioplasm,  24 
Spontaneity  of  life,  33 
Spontaneous  emission  of  semen,  1128 
Spot,  Wind,  834 

demonstration  of,  835 
form  of,  836 


Spot,  germinal,  1130 

yellow,  836 
Squint,  873 

Stannius'  experiment  on  heart  beat,  333 
Stapedius  muscle,  765 
Stapes,  767 
Starling's  theory  of  formation  of.  lymph, 

238 
Starvation,  carbon  dioxid  in,  1053 

effect  of,  1052 

elimination  of  nitrogen  in,  1053 

oxygen  ingo  in,  1053 

premortal  rise  in  excretion  of  nitrogen 
in,  1053 

purin  excretion  in,  1053 

relation  of  sulphur  to    nitrogen  in, 
1053 

urea  nitrogen  in,  1053 
Static  phase  of  respiratory  cycle,  456 

sense,  578,  730,  781 
Stationary  air,  481 
Statocvst,  781 
Statolith,  781 
Steapsin,  935,  996 
Stearin  of  milk,  902 
Stellate  cells  of  Kupffer,  939 
Stercobilin,  196,  1080 
Stercorubin,  948 
Stereoscope,  876 
Sternal  reflex,  598 
Stern  zellen  of  Kupfer,  198,  207 
Stethograph,  473 
Stethoscope,  Laennec,  757 
Stewart's  method  of  estimating  circula- 
tion time,  410 
of    measuring    volume    of    blood 
stream,  397 
Stigma,  1130 
Stigmse,  448 
Stimulants,  alcoholic,  1063 

in  diet,  1062 
Stimulation,  futurity,  34 

phenomena  of,  33 

threshold  of,  34 
Stimuli,  adaptation  state,  35 

chemical,  33 

electric,  35 

maximal,  34 

mechanical,  33 

minimal,  34 

optimum,  34 

osmotic,  33 

photic,  33 

radiating,  33 

refractory  state,  35 

strength  of,  34 

subminimal,  34 

thermal,  33 
Stirrup  bone  of  ear,  767 
Stokes'  solution,  186 
Stomach,  antrum  pylori,  1006 

bismuth  x-ray  study  of,  1008 

contents,  evacuation  of,  1009 
time  of,  1009 

fundus,  1006 


INDEX 


1181 


Stomach  fundus,  movements  of,  1005 
layer  of  circuhir  iiuisele  stnuuls,  1005 
movements  of,  1005 
musculature,  iiiniMvation  of,  1012 
outer    longitudinal    nuiscular    layer, 

1006 
pyloric  portion,  1006 
resistance  of,  to  gastric  fernuMits,  925 
teeth,  1001 

vasomotor  nerves  of,  438 
Strabismus,  873 
Striated  muscle,  42 

action  in  locomotion,  46 
String  galvanonu'ter,  Einthoven's,  286 
for  measuring  speed  of  nerve  con- 
duction, 130 
Stroma  and  hemoglobin  of  red  corpus- 
cles, separation,  181 
muscle,  85 
Stromuhr,  detection  of  vasomotor  ac- 
tion by,  420 
Ludwig's,  395 
recording,  396 
Subarachnoid  system,  717 
Subarachnoidal  space,  716 
Sublingual  salivary  glands,  908 
Submaxillary  salivary  glands,  908 
Subminimal  stimvdi,  34j 
Substance,  living,  17 
Substantia  gelatinosa,  605 

of  Rolando,  606 ' 
Substrate,  987 
Succus  entericus,  949 
Sucking,  center  for,  641 
Sugar  content  of  blood,  169 
of  milk,  902 

supply  of  body,  regulation  of,  1042 
iitilization  of,  1040 
Sulcus  primarius  of  cerebellum,  706 
Sulphates  in  urine,  1082 
Sulphur,  relation  to  nitrogen,  in  starva- 
tion, 1053 
Sunlight,  speed  of,  795 
Supplemental  air,  480 
Supraglottic  cavity,  544 
Suprarenal  bodies,  vasomotors  of,  435 
capsules,     967.       See     also    Adrenal 

glands. 
plexus,  968 
Suspensorv  ligament  of  eye,  821 
Swallowing,  998,   1001.     See  also  Deg- 
lutition. 
respiration  of,  1002 
Sweat,  896 

quantity  secreted,  896 
Sweat-glands,  895 

innervation  of,  897 
Swim-bladder  of  fish,  450 
Sylvester's  method  of  artificial  respira- 
tion, 483 
Sympathetic  system,  627 
Synapse,  110 
Synovial  fluid,  237 

Systemic  circuit  of  circulatory  system, 
259 


Systole  as  period  of  decomposition,  341 
auricular,  position  of  heart  valves  in, 
307 
I       interpolated,  343 

ventricular,   position  of  heart  valves 
in,  307 
Systolic  pressure,  intracardiac,  296 

Tactile  acuity,  736 

agnosia,  684,  697 

discrimination,  625,  736 

localization,  625,  736 

sensations,  methods  of  evoking,  735 
Talking  dog,  692 

Tallquist's  method  of  estimating  hemo- 
globin, 191 
Tambour,  Marey's,  285 
Taste  buds,  activation  of,  750 
innervation  of,  749 
power  of  reaction,  751 
structure,  748 

center,  691 

sense  of,  743 

topography  of,  751 
Taste-pore,  748 
Taurin,  87 

Taurocholic  acid,  947 
Tea,  1063 

Tectorial  membrane,  777 
Tectospinal  bundle,  anterior,  616 
Teeth,  eve,  1001 

milk,  iOOl 

permanent,  1001 

stomach,  1001 

wisdom,  1001 
Teichmann's  hemin  crystals,  188 
Telophase  of  mitosis  of  cell,  1112 
Temperature,  effect  of,  on  metabolism, 
1054 
on  muscle  contraction,  78 
on  speed  of  nerve  conduction,  132 

external,    efTect    of,    on    respiratory 
quotient,  516 

of  blood,  162 

of  body,    1093.     See  also   Body  tem- 
perature. 

reactions,  paradoxical,  743 

sense  of,  734,  741 
Temporopontine  fibers,  661 
Tendril  fibers  of  cerebellum,  708 
Tenon's  capsule,  804,  869 
Tensor  tvmpani  muscle,  765 

reflex,  "599 
Tentorium  cerebelli,  716 
Test  breakfast,  923 

tube,  Uving,  222 

tvpes,  Snellen's,  861 
Testes,  function,  982 
Testicles,  1122 
Tetania  parathyreopriva,  962 
Tetanic  current,  62 
Tetanus,  71,  72 

incomplete,  71 

of  nerve,  secondarv,  148 

Ritter's,  146 


1182 


INDEX 


Tetanus,  secondary,  104 

Wendt's,  146 
Tethelin,  980 

Thalamocortical  tract,  660 
Thalamus  opticus,  703 
Thebesius  foramina  of,  428 
Theca  folliculi,  1130 
Theine,  1063 
Theobromine,  1062 
Theorem  of  Toricelli,  348 
Thermal  stimuli,  33 

theory  of  light  stimulation  of  retina, 
840 
Thermodynamic  theory  of  muscle  con- 
traction, 49 
Thermogenesis,  1092,  1097 
Thermolysis,  1099 
Thermometry,  1089 
Thermotaxis,  1097 

nervous  mechanism  regulating,  1102 
Thiery's  method  of  obtaining  intestinal 

juice,  949 
Thirst,  754 
general,  755 
pharyngeal,  755 
sense,  743 
Thoma-Zeiss  hemocytometer,    176 
Thoracic  duct,  234 

sympathetic  nerve,  434 
system,  631 
Thorax,  aspiratory  power  of,  464 
Threshold  contraction  of  muscle,  76 

substances,  1073 
Thrombin,  213,  215 
Thrombocvtes,  159,  207,  208,  214 
Thrombogen,  170,  172,  213,  215 
Thrombokinase,  210,  213,  214 
Thromboplastic  substance,  222 
Thymus  gland,  951,  963 

extirpation  of,  effects,  964 
function,  964 
position,  963 
structure,  963 
Thyro-arytenoid  muscle,  547 
Thvroid  cartilage,  542 
gland,  951,  954 

active  principle,  nature  of,  960 
extirpation,  955 

symptoms  from,  956 
function,  961 

guanidin  metabolism  in,  963 
position,  954 
structure,  954 
Thyroidin,  960 
Thyro-oxy-indol,  960 
Thyroxin,  960 
Tidal  air,  480 

blood    and,    interchange    of    gases 
between,  488 
Tigroid  bodies,  563,  564 
Timbre  of  sounds,  759 
Time,  reflex,  585 
Tissue  nucleoproteid,  222 
oxidative  power,  508 
respiration,  507 


Tissue,  thirst,  755 
Tissue-fibrinogen,  222 
Tissue-fluid,  233 

reactions  of,  248 
Tissue-protein,  1048 
Toisson's  fluid,  177 
Tones,  fundamental,  759  , 

Tonic  contracture  of  muscle,  75 

reflexes,  592 
Tonicitj^  of  muscle,  66 

of  smooth  muscle,  83 
Tonsils,  906 

faucial,  crypts  of,  906 
function,  906 
removal  of,  effects,  907 

pharyngeal.  907 
Tonus," labyrinthine,  789 
Topler's  pump  for  extraction  of  gases 

from    blood,    Barcroft    modification, 

499 
Toricelli's  theorem,  348 
Tormina  intestinorum,  1019 
Touch  areas,  739 

illusions,  739 

sense,  734 
Toxogenic  theory  of  fever,  1107 
Toxogenin,  252 
Toxophore,  249 
Trachea,  452,  455 
Tract,  anterolateral  superficial,  618 

comma,  of  Schultze,  616 

direct,  617 

Flechsig's,  617 

Gower's,  613,  618 

olfactory,  644 

olivospinal,  616 

posterolateral,  613 

posteromedian,  613 

prepyramidal,  616 

pyramidal,  661 

rubrospinal,  616 

spinocerebellar,  617 

spinotectal,  618 

spinothalamic,  618 

thalamocortical,  660 

vestibulospinal,  616 
Tracts  of  cerebrum,  classification,  659 

of  spinal  cord,  610 

classification,  614 
Transfusion  of  blood,  230 
Translucent  bodies,  795 
Transparent  media,  795 
Traube-Hering  curves,  364,  393 
Traube's  theory  of  activation  of  oxygen, 

512 
Traumatic  epilepsy,  677 
Tremors  from  cerebellar  disease,  713 
Treppe  phenomenon  of  muscle  fatigue, 

90 
Tricuspid  valve,  268 
Trigeminus  cardiac  reflex,  327 

nerve,  534,  649 

vasomotor  reaction  of,  422 
Tritocerebron  of  crayfish,  580 
Trochlear  nerve,  649 


INDEX 


1183 


Trophic  statp  of  musclt\  07 

tlu'ury  of  cardial'.  inhil)ition.  'M\^ 
Trypsin,  '.liio 
Tubular  glands,  892 
Tuhido-raciMuoso  glands,  892 
Tunica  alhuf^inoa,  1123,  1127 

extiMiia,  415 

Miodia,  415 
Tunnel  of  Corti,  776 
'IXirck's  column,  012 
Turk's  mixture  for  counting  white  blood 

corpuscles,  201 
Twecnbrain,  004 
Tympanic  membrane,  764,  765 
Tympanum,  703,  704 
Tyrosinase,  513,  514 

Umbilical  artery,  260 

cord, 1142 

vein,  200 
Uncinate  fasciculus,  061 
Undulatory  theory  of  light,  794 
Unimolecular  reaction.  992 
Unipolar    stimulation    of    muscle    and 
nerve,  151 
effects  of,  154 
Upper  extremity,  motor  points  in,  152 
Urea,  1051 

content  of  blood,  170 

daily  excretion  of,  1085 

in  urine,  1083 

nitrogen  in  starvation,  1053 

origin  of,  in  liver,  1084 
Uremia,  1084 
Ureters.  1076 
Urethra,  1123 
Urethral  glands,  1126 
Uric  acid  in  urine,  1087 
Urinary  bladder,  1076 

nervous  control,  1077 

tubules,  absorption  of  water  from,  in 
urine  secretion,  1071 
Urine,  1080 

acetone  in,  1086 

amino-acids  in,  1087 

ammonia  in,  1086 

carbamide  in,  1083 

carbonates  in,  1082 

chlorids  in,  1081 

color,  1080 

composition,  1080,  1081 

creatin  in,  1087 

creatinin  in,  1087 

freezing  point,  1081 

general  characteristics,  1080 

hippuric  acid  in,  1087 

indican  in,  1082 

indole  in,  1082 

inorganic  constituents,  1081 

odor,  1080 

organic  constituents,  1083 

phosphates  in,  1082 

purine  bases  in,  1087 

quantity,  1080 

reaction,  1081 


Urine,     regurgitation    of,     prevention, 
1076 
secretion  of,  1064 

al)S()rpti(}n  of  water  from   urinary 

tubules  in,  1071 
Ludwig's  filtration  theory,  1007 
modern  theory,  1072 
pure  ni(!chanical  theory,  facts  con- 
tradicting, 1008 
stimulation  of,  107 
theories  of,  1067 
specific  gravity,  1080 
sulphates  in,  i082 
taste,  1080 
urea  in,  1083 
uric  acid  in,  1087 
viscosity,  1081 
Urobiligeii,  948 
Urobilin,  196,  948,  1080 
Urobilinogen,  1080 
Urochroine,  196,  1080 
Urosrythrin,  1080 
Uterus  at  end  of  pregnancy,  1138 
contraction  of,  spinal  center  for,  596 
effect  of  pituitrin  on,  978 
in  pregnancy,  1138,  1139 
virgin,  1138 
Utricle  of  ear,  771,  782 

Vagi  nerves,  function,  434 
Vagus  nerve,  654 

divided,  excitation  of  central  end, 
537 
stimulation  of  distal  end,  537 
function  of,  536 

inferior  laryngeal  branches,  535 
pressure  on,  effect  on  heart,  327 
specificity  of,  316 
superior  laryngeal  branch  of,  534 
Valsalva,  sinus  of,  272 
Valve,  Eustachian,  262 

ileocecal,  1017 
Valves,  auriculo ventricular,  268 
of  heart,  263 

arrangement,  267 
play  of,  306 
semilunar,  271 
van't    Hoff's    theory   of   activation   of 

oxygen,  511 
Vas  deferens,  1123 
Vasa  efferentia,  1123 

recta,  1123 
Vascular  system,  general  arrangement, 

253 
Vasoconstriction,  412 

theories  of,  417 
Vasoconstrictors,  412 
Vasodilatation,  412 

theories  of,  417 
Vasodilators,  412 

Vasomotor  action,  methods  of  detect- 
ing, 420 
center,  412 

activity  of,  413 
location  of,  412 


1184 


INDEX 


Vasomotor  fibers,  distribution  of,  414 
nerves  of  intestines,  437 
of  kidneys,  435 
of  liver,  438 
of  pancreas,  438 
of  spleen,  438 
of  stomach,  438 
of  suprarenal  bodies,  435 
reaction,  nature  of,  417 

of.  cervical  sympathetic  nerve,  422 
of  depressor  nerve,  427 
of  greater  splanchnic  nerve,  425 
of  sciatic  nerve,  421 
of  spinal  cord,  421 
of  trigeminus  nerve,  422 
results,  418 
Vein,  umbilical,  260 
Veins,  254 

Velocity  pressure,  350 
Vena  cava,  254 
gastrolienalis,  433 
pancreatica,  433,  933 
Venae  mesenteries;,  433 
Venous  blood  pressure,  373.     See  also 
Blood  pressure,  venous. 
pulse,  388   _ 

pathological,  390 
physiological,  388 

speed  and  character,  389 
Ventilation,  526 
negative,  539 
positive,  539 
Ventricle,  fourth,  663 
Ventricles,  bulbospiral  fibers,  266 
circular  fillers  of,  267 
discharging  period,  307 
function,  300,  302 
musculature  of,  265 
of  heart,  255 
of  Morgagni,  545 
period  of  filling,  308 
setting  period,  308 
sinospiral.  fibers,  266 
structure,  263 
Ventricular   complex   of   electrocardio- 
gram, 288 
fibrillation,  279 

systole,  position  of  heart  valves  in,  307 
Venules,  254 

Veratrin,  effect  of,  on  muscle,  79 
Vermes,  circulatory  system  of,  255 
Vermis,  inferior,  of  cerebelhun,  706 
median,  of  cerebellum,  706 
superior,  of  cerebellum,  706 
Vernix  caseosa,  function,  895 
Vertebrates,  circulatory  system  in,  256 
Verworn's  theory  of  muscle  contraction, 

50 
Vesicles,  seminal,  1126 
Vestibular  membrane,  775 
Vestibule,  aortic,  267 
Vestibulospinal  tract,  616 
V.  Helmholtz's  method  of  determining 

speed  of  nerve  conduction,  129 
Vibration  sympathetic,  of  sounds,  761 


Vibratory  energy,  728 
Vierordt  method  of  estimating  coagula- 
tion time  of  blood,  219 
Vierordt  and   Glan's  method  of  deter- 
mining hemoglobin,  190 
Virgin  uterus,  1138 
Virtual  focus,  798 

image,  798 
Visceral  musculature,  42 
nervous  system,  627 
pleura,  455 
receptors,  727,  730 
Viscosimeter,  167 
Viscosity  of  blood,  166 
variation,  167 
of  urine,  lOSl 
Vision.     See  Hiqht. 
binocular,  869,  872 
color,  879.     See  also  Color  vision. 
direct,  837 

electrical  variations  in  eye  on,  844 
far-point  of,  828 
indirect,  837 
near-point  of,  828 
Visual  acuity,  838 
after-effects,  882 
agnosia,  697 
association,  686 
axis  of  eye,  837 
axes  of  eye,  secondary,  837 
center,  connection  with  other  centers, 

687 
field,  851 
judgment,  874 
purple,  840 

bleaching  property,  842 
extraction  of,  842 
function,  843 
white,  843 
yellow,  843 
Vital  capacity,  481 
Vitalism,  238,  893 
Vitalistic  theory  of  secretion,  892 
Vitamines,  926 
Vitreous  humor,  810 
Vividiffusion,  1049 

V.  Kries  apparatus  for  recording  capil- 
lary blood  pressure,  376 
Vocal  aperture,  552 
cords,  540,  543,  550 
approximation  of,  546 
false,  543 
true,  543 
tension,  545 
registers,  553 

sounds,  characteristics,  551 
dental,  554 
explosive,  554 
friction,  554 
guttural,  554 
labial,  554 
linguopalatal,  554 
loudness,  552 
nasal,  554 
peculiarities,  553 


INDEX 


1185 


Vocal  sounds,  pitch,  552 
proiluctioii  of,  551 
(juality,  .552 
resonant,  554 
Voice,  540 

hrcakinK  of,  552 

chest,  551 

falsetto,  551 

sinking,  range,  553 
Volkmann'.s  henuxlroinomctcr,  404 
Voltaic  cell,  polarization  in,  58 
Voluntary  muscle  eoiitraction,  73 

reactions,  110 
Vomiting,  1011 

center  for,  641,  1012 

of  pregnancy,  1139 
von  Basch  sphygnioinanoineter,  366 
Vowels,  sound  production  of,  554 

Waldeyer's  neuron  doctrine  of  nervous 
system.  565 
arguments  in  favor,  567 
Waller's    ergograph    or    dvnamograph, 
81,  82 
law  of  nerve  degeneration,  119,  621 
Warm  spots  of  skin,  742 
Water,  absorption  of,  1027 

from     urinary    tubules     in     urine 
secretion,  1071 
calorimeter,  1090 
Water-rigor  of  muscle,  93 
Wave,  antiperistaltic,  1014 
peristaltic,  1014 
regular,  1014 
theory  of  nerve  conduction,  133 
Weber's  law,  733 

theory  of  muscle  contraction,  49 
Welker's  method  of  determining  quan- 
tity of  blood,  226 
Welker    and     Hoppe-Seyler's    chrono- 
metric  method  of  determining  hemo- 
globin, 190 
Wendt's  tetanus,  146 


75 


Wernicke's  sensory  aphasia,  696 
Whartonian  jolly,  1142 
Whey,  901 
Whispering,  553 

White  l)l()od  corpuscles,  199.     See  also 
Blood  corpuscles,  white. 

light,  879 

matter,  cerebral,  general  arrangement, 
658 
of  spinal  cord,   functional  basis, 
608 

of  eye,  805 

visual,  843 
Winking  reflex,  599 
Wintrichs  modification  of  Hutchinson's 

spirometer,  479 
Wirsung,  duct  of,  932 
Wisdom  teeth,  1001 
Word-blindness,  688,  696 
Word-deafness,  688,  689 
Work-adder,  diagram  of,  96 
Wrist  jerk,  599 

Xanthin,  1051 

Xanthinoxidase,  513 

A'-ray  bismuth  study  of  stomach,  1008 

Yawning,  482 

reflex,  593 
Yellow  spot,  836 

visual,  843 
Young- Helmholtz  theorv  of  color  vision, 

886 

Zollner's  lines,  878,.  879 

Zona  pellucida,  1130 

Zuntz's  indirect  method  of  determining 

cardiac  output,  302 
Zwaardemaker's  olfactometer,  745 
Zymase,  988 
Zymogen,  990 

granules,  909 
Zymoplastic  substance,  222 


COLUMBIA  UNIVERSITY  LIBRARIES 

This  book  is  due  on  the  date  indicated  below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing, 
as  provided  by  the  rules  of  the  Library  or  by  special  ar- 
rangement with  the  Librarian  in  charge. 

DATE  BORROWED 

DATE  DUE 

DATE  BORROWED 

DATE  DUE 

4[iti  2  9  in 

i^ 

MAY  $ 

1944 

mryt     • 

,JliL  1  0  1947 

AM  Mi t    n           'C/1 

WAY  ^     '-*^^ 

■J 

C28II  140)MIOO 

QP34 
Burton- Opitz 


B962 


